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Project Title	Lifestyle Risk and Resiliency Factors and Alzheimer’s Disease in Down syndrome��
Awardee	UNIVERSITY OF WISCONSIN-MADISON��
Project Number
Funding Opportunity Announcement	��
Summary	This supplement will increase the number and diversity of participants in a longitudinal study to examine four lifestyle factors - physical activity, sleep, cognitive stimulation, and social engagement - on early Alzheimer's disease (AD) neuropathology and the transition to clinical AD in adults with Down syndrome.��

Project Title	JAK Inhibition in Down Syndrome��
Awardee	UNIVERSITY OF COLORADO DENVER��
Project Number
Funding Opportunity Announcement	��
Summary	This supplement is expanding the number of participants in a clinical trial to test the safety and efficacy of a JAK inhibitor medication to treat autoimmune skin conditions like alopecia in Down syndrome.��

Project Title	Sleep and Temperature Disturbance as risk factors for Alzheimer’s Disease in Down Syndrome: A Longitudinal Study��
Awardee	NEW YORK UNIVERSITY SCHOOL OF MEDICINE��
Project Number
Funding Opportunity Announcement	��
Summary	This project is studying how age-related sleep and body temperature impacts AD biomarker progression in people with DS. Data from three timepoints across two years will be used to assess whether greater baseline obstructive sleep apnea (OSA) severity and lower baseline body temperature (Tb) will predict development of AD biomarkers and cognitive decline in adults with DS.��

Project Title	A Randomized Intervention Trial to Increase Access to Reproductive Health Services among Adolescents and Young Adults with intellectual and Developmental Disabilities��
Awardee	GRADUATE SCHOOL OF PUBLIC HEALTH AND HEALTH POLICY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This randomized controlled trial tests whether an updated socialization and sex education curriculum designed for persons with intellectual and development disabilities, including DS, can be used for effective reproductive education.��

Project Title	Septhohippocamal connectome dysfunction in Down syndrome associated with Alzheimer’s disease pathophysiology��
Awardee	NEW YORK UNIVERSITY SCHOOL OF MEDICINE��
Project Number	��
Funding Opportunity Announcement
Summary	This study seeks to close the knowledge gap on shared cellular pathophysiological mechanisms between Down syndrome (DS) and Alzheimer's disease (AD) using trisomic (Ts65Dn) mice. Analyses will identify molecular, cellular, and physiological substrates underlying vulnerability of the septohippocampal and basocortical connectomes to inform the development of new therapeutic approaches for DS and AD.��

Project Title	Development of a Novel mHealth Platform to Track Health Behaviors of Young Children with Down Syndrome��
Awardee	UNIVERSITY OF PITTSBURGH AT PITTSBURGH��
Project Number	��
Funding Opportunity Announcement	��
Summary	This award proposes to design an mHealth technology platform, "Early Child Health: Down syndrome," that assesses health behaviors and builds just-in-time interventions to support family-centered behavior change through early care.��

Project Title	Altered Hippocampal Neurogenesis and Cognition via Maneb-mediated Changes in the Thiol Redox Proteome
Awardee	UNIVERSITY OF COLORADO DENVER��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project examines gene-environment interactions affecting neurodevelopment in the Down syndrome (DS) population. Specifically, it will investigate the role and impact of thiol-redox signaling on thiol-reactive toxicants (TRT) using a robust library of pluripotent stem cells derived from DS individuals.��

Project Title	Redox and Ca2+ signaling regulation of enamel mineralization��
Awardee	NEW YORK UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project studies the dental fluorosis process to understand the interplay between mitochondrial function and enamel formation during environmental insults and to determine whether this is altered in patients with genetic disorders, such as Down syndrome, where mitochondrial dysfunction is common.��

Project Title	A Novel Approach to Molecular Cell Pathologies of Human Down Syndrome and DS-AD��
Awardee	UNIV OF MASSACHUSETTS MED SCH WORCESTER��
Project Number	��
Funding Opportunity Announcement	��
Summary	This supplement will use an inducible chromosome silencing system developed during the base award period to define the cell-type specific differences of Trisomy 21 over-expression. Deeper understanding of the cellular processes impacted, and which effects may be preventable or reversible is key to inform targets for drug development.��

Project Title	Institutional Career Development Core��
Awardee	UNIVERSITY OF WASHINGTON��
Project Number	��
Funding Opportunity Announcement	N/A��
Summary	This training award expands outreach, recruitment, and pre-application support to build a larger and more diverse cohort of scholars. Curriculum will focus on enhancing core competencies in translation science for a cross-disciplinary translational research workforce.��

Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)��
Awardee	UNIVERSITY OF PITTSBURGH AT PITTSBURGH��
Project Number	��
Funding Opportunity Announcement
Summary	This ABC-DS project will study how Alzheimer disease (AD) in Down syndrome (DS) may parallel sporadic AD and identify genetic modifiers of the development of Alzheimer disease (AD) in people with Down syndrome.��

Project Title	Investigating and targeting apolipoprotein E4 in Down syndrome associated Alzheimer’s disease��
Awardee	UNIVERSITY OF COLORADO DENVER��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will use human induced pluripotent stem cell (iPSC)-derived cerebral organoid (CO) models of Down syndrome and Alzheimer's disease along with a mouse model of Down syndrome to evaluate whether previously identified drug candidates can block the development of Alzheimer's disease phenotypes in Down syndrome.��

Project Title	DS-ARC: A Remote Digital Cognitive Assessment for Down Syndrome-Associated Alzheimer’s Disease��
Awardee	WASHINGTON UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This DS-ARC (Down syndrome- Ambulatory Research in Cognition) study will develop and validate a smartphone-based digital cognitive assessment designed specifically for participants at risk for Down syndrome-associated Alzheimer’s disease (DS-AD).��

Project Title	Vitamin E Trial in Persons with Down Syndrome: Sharing Data with the Research Community��
Awardee	COLUMBIA UNIVERSITY HEALTH SCIENCES��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will de-identify and transfer data collected from the 10-year Vitamin E Trial in Persons with Down Syndrome to the NIH-funded investigation of Co-occurring conditions across the Lifespan to Understand Down Syndrome (INCLUDE) Project.��

Project Title	The paradox of myeloid leukemia of Down syndrome��
Awardee	WAYNE STATE UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study will investigate the increased sensitivity to AraC in children with myeloid leukemia associated with DS (ML-DS) and the role of chromosome 21-localized gene cystathionine-ß-synthase (CBS) in this increased sensitivity.��

Project Title	A Physiologically Integrated Approach to Studying Mechanisms of Speech Production and Swallow Function in Down Syndrome��
Awardee	PENNSYLVANIA STATE UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study will examine the mechanisms of swallow and speech production in individuals with Down syndrome and the interrelations between domains of oropharyngeal structure, muscle strength, somatosensation, measures of cognition, perception and language, and the underlying neurology.��

Project Title	Molecular mechanisms of oral deficiencies in Down syndrome��
Awardee	NEW YORK UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study seeks to determine how salivary gland and enamel formation are altered on a molecular level in individuals with Down syndrome.��

Project Title	Evaluating Assessment and Medication Treatment of ADHD in Children with Down Syndrome��
Awardee	CINCINNATI CHILDRENS HOSP MED CTR��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study will assess the short- and long-term safety and efficacy of stimulant treatment in children with Down syndrome and ADHD with a specific focus on cardiac safety.��

Project Title	Leveraging technology to identify outcome measures for young children with Down syndrome��
Awardee	UNIVERSITY OF WISCONSIN-MADISON��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study will evaluate the use of language samples collected remotely by caregivers using digital technology to serve as outcome measures for young children with Down syndrome.��

Project Title	Investigating epigenetic mechanisms in Down syndrome using human cellular models��
Awardee	BROAD INSTITUTE, INC.��
Project Number
Funding Opportunity Announcement	��
Summary	This project will investigate the variation in genome-wide gene expression and DNA methylation patterns in donor individuals with Down syndrome.��

Project Title	A heterochronic model for birth defects in Down Syndrome��
Awardee	UNIVERSITY OF CHICAGO��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study aims to determine whether the unifying cause of birth defects in Down syndrome is heterochronic timing control of organ-specific progenitor differentiation, resulting in precocious differentiation, a reduction of organ-specific progenitors, morphogenesis failure and birth defects in multiple organs.��

Project Title	A mosaic Down syndrome model system comparing isogenic trisomic/disomic cells to unmask trisomy-21 related genomic, epigenomic, and senescence changes acquired across the lifespan����
Awardee	VIRGINIA COMMONWEALTH UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study seeks to identify biomarkers and therapeutic targets for health conditions at an earlier age in people with mosaicism for trisomy 21 (mDs).��

Project Title	Feasibility and outcome measures for infants with Down syndrome: Advancing clinical trial readiness for a harness-based mobility intervention��
Awardee	BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will examine the feasibility and acceptability of a home-based mobility-related intervention specifically tailored for infants with Down syndrome.��

Project Title	2023 International Mosaic Down Syndrome Association Community-Empowered Research and Retreat Weekend: Increasing Partnerships, Cohorts, and Diversity for Research Related to Down Syndrome��
Awardee	VIRGINIA COMMONWEALTH UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This award supports the “2023 International Mosaic Down Syndrome Association Community-Empowered Research and Retreat Weekend: Increasing Partnerships, Cohorts, and Diversity for Research Related to Down Syndrome” meeting which focuses on providing information, resources, support, and research opportunities for people who have mosaic Down syndrome (mDs).��

Project Title	Data Science for Diverse Scholars in Down Syndrome Research (DS3)��
Awardee	CHILDREN'S HOSP OF PHILADELPHIA��
Project Number	��
Funding Opportunity Announcement	��
Summary	This supplement supports an immersive summer course in data sciences known as the Data Science for Diverse Scholars in Down Syndrome Research (DS3) that provides training in the basics of generation, identification, and collection of high content multidimensional datasets; their management, analysis, and visualization, included cloud-based analytics; as well as development of key professional skills required for the career advancement of diverse trainees.��

Project Title	Investigation and deployment of novel Bayesian inference algorithms in CAVATICA for identifying genomic variants underlying congenital heart defects in Down syndrome individuals��
Awardee	MISSOURI UNIVERSITY OF SCIENCE & TECHNOLOGY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study will evaluate clinical and whole genome sequencing (WGS) data by the Kids First (KF) and INCLUDE programs to identify significant variants underlying congenital heart defects (CHD) in patients with and without Down syndrome.��

Project Title	Defining the role of enteric nervous system dysfunction in gastrointestinal motor and sensory abnormalities in Down syndrome��
Awardee	UNIVERSITY OF COLORADO DENVER��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will investigate whether progressive injury to the enteric nervous system drives colonic secreto-motor and permeability (SMP) abnormalities in Down syndrome and determine the effects of experimental colonic inflammation and microbiome manipulation in a mouse model of Down syndrome.��

Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) - KUMC Field Site Supplement��
Awardee	UNIVERSITY OF PITTSBURGH AT PITTSBURGH��
Project Number	��
Funding Opportunity Announcement
Summary	This ABC-DS supplement will support joint pattern analyses of baseline and longitudinal Aβ and tau PET neuroimaging data acquired in sibling controls and individuals with DS to identify spatiotemporal patterns of Aβ and tau uptake that are more sensitive to progressive pathophysiological brain changes.��

Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS) - Gait Supplement�� ��
Awardee	UNIVERSITY OF PITTSBURGH AT PITTSBURGH��
Project Number	��
Funding Opportunity Announcement
Summary	This supplement will assess gait as a possible clinical biomarker for dementia in people with Down Syndrome.��

Project Title	Lifestyle and Alzheimer’s Disease in Down Syndrome- Life Stressors Supplement��
Awardee	UNIVERSITY OF WISCONSIN-MADISON��
Project Number
Funding Opportunity Announcement	��
Summary	This supplement to the “Lifestyle Risk and Resiliency Factors and Alzheimer’s Disease in Down syndrome” project will examine the effect of adverse childhood events (e.g., parent divorce, abuse/neglect, poverty) and recent life stressors (e.g., job termination, new staff, death of family member) on the timing of AD pathology and symptomology in people with Down syndrome.��

Project Title	Microbial Impact on Neurodegeneration in Alzheimer’s Dementia: MIND-AD - INCLUDE Admin Suppl��
Awardee	JOHNS HOPKINS UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This supplement will recruit 500 individuals with Down syndrome in the mid-Atlantic area to a study to investigate the association of antibodies to HSV- 1, HSV-2, CMV, EBV, TOX and SARS-CoV-2 in blood with cognitive and functional outcomes, blood-based Alzheimer’s disease biomarkers, and measures of biological aging.��

Project Title	Determining cell-specific mechanisms that drive aberrant bone regeneration in Down syndrome��
Awardee	TEXAS A&M AGRILIFE RESEARCH��
Project Number	��
Funding Opportunity Announcement
Summary	This study will use a mouse model of Down syndrome to establish an expansive transcriptome database during bone regeneration of terminal phalanx, decouple the sex related impacts and age-related impacts on osteoclasts and osteoblasts during bone regeneration, and determine the capacity for bone anabolic agents to rescue bone regeneration in DS mice.��

Project Title	Intraindividual cognitive variability in aging adults with Down syndrome: associations with Alzheimer’s disease plasma biomarkers, neuropathology and clinical dementia��
Awardee	WASHINGTON STATE UNIVERSITY��
Project Number
Funding Opportunity Announcement
Summary	This project will use ABC-DS project data to characterize the association between intraindividual cognitive variability (IICV), Alzheimer’s disease biomarkers, and dementia in adults with DS.��

Project Title	Assessment of Physical Activity for Alzheimer’s Disease Research in Down Syndrome��
Awardee	UNIVERSITY OF KANSAS MEDICAL CENTER��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will develop and validate cut points of an ActiGraph portable accelerometer for the measurement of physical activity in patients with DS and explore how physical activity level might impact cognitive function, sleep quality, and biomarkers for Alzheimer’s disease in adults with DS.��

Project Title	T cells promoting transitions toward autoimmunity��
Awardee	BENAROYA RESEARCH INST AT VIRGINIA MASON��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will determine whether pathogenic precursors are present in the naïve T cell compartment of individuals, including those with DS, at risk for autoimmune disease compared to non-risk individuals. The project further aims to identify cell types that harbor genetic risk for disease transitions and identify underlying pathways that support pathogenic precursor T cells as well identify external factors that contribute to the transition of pathogenic precursors to effectors.��

Project Title	Investigating monocyte dysfunction in Down Syndrome��
Awardee	BENAROYA RESEARCH INST AT VIRGINIA MASON��
Project Number	��
Funding Opportunity Announcement	��
Summary	This administrative supplement will investigate monocytes and toll-like receptor (TLR) response in a DS population with juvenile arthritis and compare the data with R01 AR076242 project data for better understanding of inflammatory arthritis seen in children with Down syndrome.��

Project Title	Speech Perception and Auditory Abilities in Infants, Children, and Adults with Down syndrome��
Awardee	FATHER FLANAGAN'S BOYS' HOME��
Project Number
Funding Opportunity Announcement	��
Summary	This project will characterize the speech perception and auditory abilities of infants, children, and adults with Down syndrome by evaluating phoneme perception, testing the hypothesis that maturation of selective listening strategies follows a delayed time course of development, and characterize the ability to recognize speech in the presence of competing background sounds.��

Project Title	Autism in Young Children with Down Syndrome��
Awardee	COLORADO STATE UNIVERSITY��
Project Number	��
Funding Opportunity Announcement
Summary	This study will identify markers of autism spectrum disorder (ASD) by focusing on two areas; developmental presentation during early childhood and co-occurring biomedical conditions and model the relationship between developmental and biomedical factors at different age groups to generate recommendations for ASD screening protocols for children with DS ages 18 to 45 months.��

Project Title	Leveraging Claims Data to Compare Disparities in Health Outcomes for Autistic People and People with Down Syndrome��
Awardee	DREXEL UNIVERSITY��
Project Number	��
Funding Opportunity Announcement
Summary	This research will address the preventable health outcomes investigating modifiable health determinants for autistic individuals, evaluating inequities in health and health services, and examining the relations between health services delivery and health outcomes. ��

Project Title	Leveraging E-education to Advance Assent and Decision-Making Involvement in Down Syndrome��
Awardee	CHILDREN'S HOSP OF PHILADELPHIA��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will develop and pilot an interactive mobile friendly web application to interview caregivers and adolescent and young adults with DS to study the feasibility and acceptability of incorporating multi-media materials in real-world assent/consent implementation.��

Project Title	Infant arousal as a predictor of functional outcomes in Down syndrome (DS)��
Awardee	UNIV OF NORTH CAROLINA CHAPEL HILL��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will generate a novel multimodal arousal based objective biomarker of cognitive, social, and sensory outcomes in infants with DS by identifying patterns related to social and nonsocial arousal and habituation to stimulus in response to specific, well controlled stimuli.��

Project Title	Cardiogenesis: Molecular Mechanisms��
Awardee	J. DAVID GLADSTONE INSTITUTES��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will investigate the molecular mechanisms underlying valvuloseptal defects in a Dp1Tyb mouse model mouse and human trisomy 21 iPS cell line by identifying trisomy genes duplicated in DS that are necessary and sufficient for modulation of iPS-derived AV myocardium, determine the mechanism by which transcription factors affect transcriptional and epigenetic signatures in AV myocardium, and determine the in vivo dose dependency of candidate genes on cardiogenesis.��

Project Title	Exploring the Role of the anterior SHF in AVSD Pathogenesis��
Awardee	MEDICAL UNIVERSITY OF SOUTH CAROLINA��
Project Number	��
Funding Opportunity Announcement	��
Summary	This supplement will test the role of the anterior and posterior second heart field (SHF) in the pathogenesis of atrial and ventricular defects using DS mouse models and initiate single cell RNAseq experiments to gain insight into the molecular mechanisms involved in the pathogenesis of atrioventricular septal defects (AVSDs). This will lead to strategies to prevent and/or treat this severe congenital defect.��

Project Title	Elucidating CHD in Down Syndrome with Cardiac Organoids and 3D Genome Architecture��
Awardee	STANFORD UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study will utilize 3D- vascularized cardiac organoids, multi-omics analysis, and 3D genome architecture analysis to examine differences in gene expression and developmental pathways between individuals with DS and congenital heart disease (CHD) and those without CHD. The outcomes will facilitate the development of novel therapeutic strategies to address cellular abnormalities in the affected heart.��

Project Title	Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome.��
Awardee	CHILDREN'S HOSPITAL OF LOS ANGELES��
Project Number
Funding Opportunity Announcement	��
Summary	This project will create a validated screening tool for assessing the risk of early cerebrovascular disorder in persons with Down syndrome by comparing blood pressure readings and other biometric tools to assess predictive validity of these measures in the prediction of cerebrovascular disease (CeVD). In addition, the project will explore the role of systemic and vascular inflammatory biomarkers in the development of CeVD.��

Project Title	DCC supplement for Experimental Models Portal and Enhanced Security��
Awardee	CHILDREN'S HOSP OF PHILADELPHIA��
Project Number	��
Funding Opportunity Announcement	��
Summary	This supplement will develop a pilot researcher portal for sharing and analysis of data from experimental models of DS, conduct beta testing of the pilot portal, and enhance the security framework of the existing Data Hub.��

Project Title	Function of RUNX1 in diverse Down syndrome tissues��
Awardee	UNIVERSITY OF COLORADO��
Project Number	��
Funding Opportunity Announcement	��
Summary	This supplement will study the contribution of the RUNX1 gene to the altered blood cell composition in individuals with Down syndrome by assessing the relevance of RUNX1 splicing equilibrium on the different outcomes of DS-derived iPSC and lymphoblastoid cell differentiation and homeostasis.��

Project Title	Establishing foundational tools and datasets for investigation of NSD1 gene function in neural development��
Awardee	BROAD INSTITUTE, INC.��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project proposes to develop novel human induced pluripotent stem cell (iPSC) tools to study NSD1 haploinsufficiency and to generate pilot data on NSD1 molecular function in human neurons. These tools and datasets will be used to accelerate our understanding of how NSD1 haploinsufficiency drives the neurodevelopmental phenotypes observed in Sotos syndrome.��

Project Title	Investigating the Mechanism of Optic Nerve disorders associated with Down Syndrome��
Awardee	VIRGINIA POLYTECHNIC INST AND ST UNIV��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will use two independent murine DS models (Ts65Dn and DP16) to investigate retinal circuit and retinogeniculate connectivity using measures to assess vision defects and visual circuit formation as well as test if acid arachidonic acid (ARA) supplementation ameliorates known defects in visual acuity and contrast sensitivity in these two DS mouse models.��

Project Title	SIM2 Regulation of Mitochondrial Dysfunction in Down Syndrome��
Awardee	TEXAS A&M AGRILIFE RESEARCH��
Project Number	��
Funding Opportunity Announcement
Summary	This award will study the increased expression of Sim2 in DS skeletal muscle and how it promotes mitochondrial activity, resulting in increased oxidative stress and mitochondrial dysfunction to help define the mechanism of mitochondrial dysfunction in DS.��

Project Title	Randomized Control Trial of oxygen therapy in Children and Adolescents with Down Syndrome and Obstructive Sleep Apnea��
Awardee	CINCINNATI CHILDRENS HOSP MED CTR��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will investigate potential oximetry measurement biases by race/ethnicity and skin pigmentation in children with DS who are potential candidates for oxygen supplementation.��

Project Title	Sleep abnormalities in Down Syndrome-related Alzheimer's disease��
Awardee	UNIVERSITY OF COLORADO��
Project Number	��
Funding Opportunity Announcement	��
Summary	This award focuses on APP and RCAN1 overexpression as mechanistic links between DS and AD-related disease involved in sleep disruption, circadian dysregulation, cognition impairment, and synaptic deficits to determine the extent that these contribute to sleep disturbances in DS.��

Project Title	Anti-tumor and autoimmunity signatures in Down syndrome��
Awardee	BENAROYA RESEARCH INST AT VIRGINIA MASON��
Project Number	��
Funding Opportunity Announcement	��
Summary	This administrative supplement will support the continued recruitment of adults with DS with and without co-occurring autoimmune disease to an existing biorepository and seek to define an optimal anti-tumor signature by identifying shared characteristics of the immune architecture between people with DS and those treated with an immune checkpoint inhibitor (ICI) who develop immune related adverse events (irAE).��

Project Title	Maternal acetaminophen use and childhood cancer��
Awardee	UNIVERSITY OF NORTH TEXAS��
Project Number
Funding Opportunity Announcement	��
Summary	This project will utilize data from a large cohort of Taiwanese children to examine comorbid conditions in children with Down syndrome to improve screening guidelines and management of patient care.��

Project Title	Integrating Epidemiologic and Genomic Data to Elucidate the Genetic Overlap Between Congenital Anomalies and Pediatric Cancer��
Awardee	UNIVERSITY OF TX MD ANDERSON CAN CTR��
Project Number	��
Funding Opportunity Announcement
Summary	This project will elucidate the overlap between congenital anomalies and pediatric cancer by leveraging and integrating existing datasets, including 1) the Gabriella Miller Kids First Pediatric Research Program; 2) the All of Us Research Program; and 3) the GOBACK Registry Linkage Birth Cohort to identify new congenital anomaly-pediatric cancer (CA-PC) patterns and confirm previously reported patterns, identify novel pleiotropic genes harboring rare, pathogenic variants responsible for specific CA-PC patterns, and describe the landscape of somatic alterations in pediatric cancers that result from pathogenic CA-PC variants.��

Project Title	Predoctoral Training Grant in Pharmacology INCLUDE Down Syndrome Supplement��
Awardee	UNIVERSITY OF COLORADO DENVER
Project Number	��
Funding Opportunity Announcement	��
Summary	This INCLUDE supplement application to the existing parent program will enhance the already robust environment for training graduate students in areas of scientific enquiry germane to Down syndrome and its co-occurring conditions with a comprehensive didactic component, 3 laboratory rotations, a strong emphasis on student presentations in seminar settings, and a wide choice of thesis research options.����

Project Title	Predoctoral Training Program in Molecular and Cellular Biology (INCLUDE Down Syndrome Supplement)��
Awardee	UNIVERSITY OF COLORADO DENVER
Project Number	��
Funding Opportunity Announcement	��
Summary	This supplement will support four additional T32 funded students in the Molecular Biology (MOLB) Program at the University of Colorado Anschutz Medical Campus, with a goal of supporting new high-quality scientist dedicated in pursuing biomedical research to enhance our understanding about the causes and potential treatments of Down Syndrome.��

Project Title	Predoctoral Training in the Genetics of Development, Disease and Regeneration��
Awardee	UNIVERSITY OF COLORADO DENVER
Project Number	��
Funding Opportunity Announcement	��
Summary	The award will support a program to train a diverse group of scientists to solve problems relevant to human health, including developmental diseases through research in genetics, development, and cell and stem cell biology.����

Project Title	Predoctoral Training Program in Signaling and Cellular Regulation INCLUDE Down Syndrome Supplement��
Awardee	UNIVERSITY OF COLORADO��
Project Number	��
Funding Opportunity Announcement	��
Summary	This supplement will support training to prepare the next generation of scientists who will conduct high quality research in biomedical sciences, to understand fundamental mechanisms in signaling and cellular regulation, which is key to the discovery of new therapeutic treatments for human diseases such as cancer, diabetes, inflammation, heart disease, immunological and neurological disorders, and birth defects, and forms a foundation for modern research in biology and medicine relevant to alterations observed in Down syndrome and its co-occurring conditions.��

Project Title	Self-Supporting Nasopharyngeal Airway (ssNPA) Treating Upper Airway Obstruction in Hypotonia��
Awardee	UNIVERSITY OF MICHIGAN AT ANN ARBOR��
Project Number	��
Funding Opportunity Announcement	��
Summary	This award will test an enhanced version of a self-supported nasopharyngeal airway (ssNPA) device that bypasses challenging, diffuse, multilevel upper airway obstruction for acceptability and tolerability in hypotonic patients undergoing polysomnography. The test will optimize insertion, adherence, and compliance protocols for preparation of the R33 phase which will assess a powered cohort looking at and quality of life outcomes.����

Project Title	Trisomy 21 Model Atlas��
Awardee	UNIVERSITY OF COLORADO DENVER��
Project Number	��
Funding Opportunity Announcement	��
Summary	This study proposes to generate an atlas of gene expression programs for 10 organs affected by Trisomy 21 and to define the impact of Trisomy 21 on organ development and pathophysiology at the cellular level. This project will allow cross-validation of findings in mouse models of DS with human cell types and provide a valuable set of resources to build our understanding of molecular and cellular mechanisms underlying DS.��

Project Title	Trophoblast progenitor heterogeneity and function in normal and Trisomy 21-affected placentae��
Awardee	UNIVERSITY OF CALIFORNIA, SAN DIEGO��
Project Number	��
Funding Opportunity Announcement	��
Summary	This project will study the role of human placenta in maintaining the proper environment for fetal growth, with an emphasis on studying trophoblast stem cells and organoids in early gestation human placenta derived from normal and trisomy 21-affected pregnancies. Findings will provide insights into the cellular mechanisms of placental dysfunction in pregnancies affected by Trisomy 21.��

Project Title	Development and Validation of the Down Syndrome Regression Rating Scales��
Awardee	VIRGINIA COMMONWEALTH UNIVERSITY��
Project Number	��
Funding Opportunity Announcement	��
Summary	This award seeks to develop, test, and refine the Down Syndrome Regressive Rating Scale (DSRRS) for Down Syndrome Regression Disorder, a rare but highly debilitating disorder, in a multisite trial. This project will use robust methods to ensure construct validity and reliability with the goal of publishing DSRRS as an open-source measure to enable timely, cost-efficient screening of individuals in need of further evaluation.��

Project Title	Telehealth-delivered outcome measures for Spanish- and English-speaking people with Down syndrome��
Awardee	UNIVERSITY OF CALIFORNIA AT DAVIS��
Project Number	��
Funding Opportunity Announcement	��
Summary	This award will validate the Expressive Language Sampling Narrative (ELS-N) and examine its psychometric properties across two delivery settings. Expressive language impairments are prevalent in Down syndrome populations and impact daily functioning. As many clinical trial outcome measures are only in English, practical assessment tools are needed for in-clinic and telehealth practices to support Spanish-speaking participants and address limitations in generalizability.��

Project Title	CaMKII nitrosylation in the age-related decline of synaptic plasticity
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will use knockout mouse models to investigate potential roles of the APP protein in synaptic dysfunction in Down syndrome prior to manifestations of Alzheimer’s disease, which may lead to new therapeutic strategies for both conditions.

Project Title	Auditory function, cognition, language and brain structure in Down Syndrome
Awardee	University of Wisconsin, Madison
Project Number
Funding Opportunity Announcement
Summary	This study will assess how measures of hearing loss relate to auditory processing, language function, and brain structure in individuals with Down syndrome to inform clinical diagnosis and intervention of hearing disorders in individuals with the condition.

Project Title	Sleep Disruption and Alzheimer’s Disease Pathology
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will use mouse models to examine the extent to which the proteins APP or RCAN1 contribute to sleep disturbances in Down syndrome, thus establishing a mechanistic link between Down syndrome and early-age onset Alzheimer’s disease.

Project Title	T21RS Meeting June 2022 Long Beach, California
Awardee	University of California, Irvine
Project Number
Funding Opportunity Announcement	��
Summary	This award supported American-based junior investigators, postdoctoral fellows, and graduate students to attend the Fourth International conference of the Trisomy 21 Research Society in June 2022.

Project Title	Home sleep apnea testing compared to in-lab polysomnography for the evaluation of obstructive sleep apnea in children
Awardee	Children’s Hospital of Philadelphia
Project Number
Funding Opportunity Announcement	��
Summary	This clinical trial will compare home sleep apnea testing with overnight polysomnography (hospital-based sleep study) in terms of its accuracy and impact on therapeutic decision-making for children being evaluated for obstructive sleep apnea.

Project Title	Enriching medical phenotypes and environmental traits in the large DS360 Down syndrome cohort
Awardee	Emory University
Project Number
Funding Opportunity Announcement
Summary	This award will support efforts to enrich data from an established Down syndrome cohort study by recontacting participants to complete an updated medical history form. It will also support efforts to harmonize these data with other resources to ensure maximum impact of the dataset.

Project Title	Iron Metabolism in Ts65Dn mice, a Model of Down syndrome
Awardee	Syracuse University
Project Number
Funding Opportunity Announcement	��
Summary	This study will delineate sex and age-related alterations in iron homeostatic regulation over the adult lifespan of a mouse model of Down syndrome and associate changes in iron regulation with tissue iron levels and oxidative stress.

Project Title	Advanced clinical practice and establishing foundational theory for auditory function in individuals with Down syndrome
Awardee	Father Flanagan’s Boys’ Home
Project Number
Funding Opportunity Announcement	��
Summary	This study will define the prevalence, type, and trajectory of hearing loss for individuals with Down syndrome and establish foundational theory regarding their functional auditory abilities guided by a model of speech perception.

Project Title	DYRK1A interaction network in development and disease
Awardee	Virginia Commonwealth University
Project Number
Funding Opportunity Announcement	��
Summary	This study will characterize the role of novel gene interaction partners in the function of the DYRK1A gene, an important gene on chromosome 21, and embryo development in the frog model Xenopus laevis.

Project Title	Mechanisms of Down syndrome-associated swallowing dysfunction in mouse models
Awardee	University of Wisconsin, Madison
Project Number
Funding Opportunity Announcement	��
Summary	This study will investigate how aging impacts swallowing function in adult mouse models of Down syndrome and generate new mouse models to reveal the molecular underpinnings of swallowing dysfunction associated with Down syndrome.

Project Title	Speech perception and auditory abilities in infants, children, and adults with Down syndrome
Awardee	Father Flanagan’s Boys’ Home
Project Number
Funding Opportunity Announcement	��
Summary	This study will evaluate language perception in infants, children, and adults with Down syndrome, test whether selective listening strategies are delayed in individuals with Down syndrome, and characterize speech perception in background noise in children and adults to inform models of speech perception in those with Down syndrome.

Project Title	Systematic functional study of 21st chromosome ortholog overexpression in C. elegans
Awardee	University of Texas, Austin
Project Number
Funding Opportunity Announcement	��
Summary	This study will use an innovative screening strategy to systematically study the consequence of adding and subtracting each of the 200 genes on the 21st chromosome in the worm model, C. elegans.

Project Title	Systematic functional study of 21st chromosome ortholog overexpression in C. elegans
Awardee	University of Texas, Austin
Project Number
Funding Opportunity Announcement	��
Summary	This diversity supplement will support a graduate student from an underrepresented group to study specific genes from human chromosome 21 that are overexpressed in Down syndrome and explore their role in immune cell activation in the worm model, C. elegans.

Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)
Awardee	University of Pittsburgh at Pittsburgh
Project Number
Funding Opportunity Announcement	��
Summary	This supplement will allow ABC-DS to examine the brains of 30 people with Down syndrome and make comparisons to 20 age-matched controls from the NIH Neurobiobank to provide a rich dataset for testing hypotheses and set the stage for neuropathology studies in ABC-DS brain donations.

Project Title	Advancing the cloud-based data access and interoperability infrastructure of the INCLUDE data ecosystem
Awardee	Children’s Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	This supplement will support the INCLUDE Data Hub to design, build, and integrate a clearinghouse to create a secure and compliant system to make available controlled data within the INCLUDE Data Hub. These investments in infrastructure will empower more researchers to access richer datasets, increasing the utility of the Down syndrome Data Hub.

Project Title	Data Science for Diverse Scholars in Down Syndrome Research (DS3)
Awardee	University of Colorado
Project Number
Funding Opportunity Announcement
Summary	This supplement will fund the development of an immersive summer course in data sciences known as the Data Science for Diverse Scholars in Down Syndrome Research (DS3), which will provide training in the basics of generation, identification, and collection of multidimensional datasets; their management, analysis, and visualization; as well as development of key professional skills required for the career advancement of diverse trainees.

Project Title	Role of early motor experience in infants with Down syndrome
Awardee	Georgia State University
Project Number
Funding Opportunity Announcement
Summary	This supplement project will add the parameters of physical activity and sleep to their investigations of the effect of gross motor and fine motor interventions on the cognitive development of infants with Down syndrome and provide mentorship to diverse undergraduate students in research training.

Project Title	Role of early motor experience in infants with Down syndrome
Awardee	Georgia State University
Project Number
Funding Opportunity Announcement
Summary	This supplement will explore the use of motion capture and computer vision/machine learning technology to examine infant movement in infants with Down syndrome and will support the training and career development of two underrepresented undergraduate students and two graduate students on the project.

Project Title	Executive dysfunction as a treatment target for DS clinical trials: An evaluation of its real-world and neural correlates
Awardee	Drexel University
Project Number
Funding Opportunity Announcement
Summary	This supplement will extend the parent award, which studies ties between executive function (the ability to self-regulate and complete complex tasks) and employment, by focusing on work readiness and the potential contextual and environmental factors that influence vocational outcomes in individuals with Down syndrome.

Project Title	CTRP and Metabolic Control
Awardee	Johns Hopkins University
Project Number
Funding Opportunity Announcement
Summary	This supplement will examine the mechanistic underpinnings of the metabolic disturbance, obesity, and diabetes that often co-occur in Down syndrome (DS) via transcriptomic analysis in liver, muscle, pancreas, and adipose tissue using two mouse models of DS (TcMAC21 and Ts65Dn).

Project Title	FASEB SRC: The Consequences of Aneuploidy: Honoring the Contributions of Angelika Amon
Awardee	Federation of American Societies for Experimental Biology
Project Number
Funding Opportunity Announcement
Summary	This award supported the conference “The Consequences of Aneuploidy: Honoring the Contributions of Angelika Amon” in September 2022 which highlighted recent advances in the fast-moving field of aneuploidy biology related to chromosome imbalance.

Project Title	Behavior Measure for Children and Adolescents with Down Syndrome
Awardee	Cincinnati Children’s Hospital Medical Center
Project Number
Funding Opportunity Announcement
Summary	This project will develop and validate a novel behavioral outcome measure, the Behavior Inventory for Down Syndrome (BIDS) for children and adolescents with Down syndrome, in both English and Spanish.

Project Title	Suppressing Aneuploidy-associated phenotypes in Down syndrome
Awardee	University of Massachusetts Medical School, Worcester
Project Number
Funding Opportunity Announcement
Summary	This study will examine the mechanisms through which aneuploidy affects the nuclear membrane, investigating how an abnormal nucleus contributes to the pathophysiology of trisomy 21, and targeting the sphingolipid biochemical pathway and its role in premature aging in trisomy 21 cells.

Project Title	Transdiagnostic Associations Across Developmental Disorders
Awardee	University of Houston
Project Number
Funding Opportunity Announcement
Summary	This study will establish a large sample of children in Zambia with developmental disabilities, including Down syndrome, and will study the cause of these conditions, describe their features, and document how they are regarded and treated within the community, to generate recommendations for policy makers.

Project Title	Investigating injury response and bone regeneration in Down syndrome mouse models
Awardee	Texas A&M University
Project Number
Funding Opportunity Announcement
Summary	This study will investigate the bone healing response in mouse models of Down syndrome to study tissue and bone injury repair and determine the extent to which prostaglandin signaling, known to enhance bone formation and crucial for wound healing, may be disrupted in Down syndrome.

Project Title	Mechanisms for cell signaling in the control of cardiomyogenesis
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This study will explore how increased interferon signaling in human stem cell lines and animal models of Down syndrome down-regulates the Wnt/β-Catenin pathway during heart development and contributes to congenital heart defects.

Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)
Awardee	University of Pittsburgh at Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This project will continue to follow a diverse cohort of adults with Down syndrome to identify amyloid, tau, and other biomarkers of neurodegeneration, as well as risk and resilience factors that modify the development of Alzheimer’s disease in this population to lay the framework for clinical trials.

Project Title	Cerebrovascular contributions to Alzheimers disease in adults with Down Syndrome
Awardee	Columbia University Health Sciences
Project Number
Funding Opportunity Announcement
Summary	This project will examine neuroimaging, blood-based, and neuropathological markers of the vascular contributions to cognitive impairment and Alzheimer's disease in adults with Down syndrome.

Project Title	Mechanistic and functional dissection of inflammaging in Down syndrome
Awardee	Benroya Research Institute at Virginia Mason
Project Number
Funding Opportunity Announcement
Summary	This study will leverage a novel biorepository of cells from people with Down syndrome to examine how the condition causes advanced immune aging (“inflammaging”) by dysregulating a type of immune cell known as CD4+ T cells.

Project Title	Obesity Prevention Targets for Down Syndrome
Awardee	Colorado State University
Project Number
Funding Opportunity Announcement
Summary	This study will examine how motor skills development, feeding abilities, dietary intake, other co-occurring conditions, and the family context provide protection or risks for obesity in toddlers and preschoolers with Down syndrome.

Project Title	The Role of CSF Dynamics in Infant Brain and Behavioral Development in Down Syndrome and Related Neurodevelopmental Disorders
Awardee	University of North Carolina, Chapel Hill
Project Number
Funding Opportunity Announcement
Summary	This career development award will study cerebrospinal (spinal) fluid characteristics in Down syndrome and related neurodevelopmental disorders across the first two years of life to determine the relationship between cerebrospinal fluid physiology (such as volume and flow) and later neural and clinical features.

Project Title	ABC-DS MOMs’ Supplement (Modification of Maternal AD risk in DS)
Awardee	University of Pittsburgh at Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This supplement will examine blood-based Alzheimer’s disease biomarkers and genetic factors among parents of adults with Down syndrome to explore the impact of a range of genetic factors on the risk of Alzheimer’s disease to both the mothers and their children with Down syndrome.

Project Title	Precision Medicine for Inflammatory Treatment for Alzheimer’s Disease in Down Syndrome
Awardee	University of California, San Diego
Project Number
Funding Opportunity Announcement
Summary	This supplement will use well-characterized, biobanked plasma samples from the legacy Vitamin E in Down syndrome clinical trial to characterize Alzheimer’s disease biomarkers and develop a precision medicine approach for the use of anti-inflammatory medications in Down syndrome trials.

Project Title	Predoctoral Training Grant in Pharmacology INCLUDE Down Syndrome Supplement
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will enhance the already robust environment at the University of Colorado Denver to train graduate students in pharmacology, an area of scientific inquiry relevant to Down syndrome and its co-occurring conditions.

Project Title	Predoctoral Training Program in Molecular and Cellular Biology (INCLUDE Down Syndrome Supplement)
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will support five PhD students in the field of molecular and cellular biology at the University of Colorado Denver in collaboration with the Linda Crnic Institute for Down syndrome for one year; these students will pursue a research project focused on Down syndrome.

Project Title	Predoctoral Training in the Genetics of Development, Disease and Regeneration
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will support three PhD students in the field of genetics of development, disease, and regeneration at the University of Colorado Denver, with an emphasis on trainees studying Down syndrome topics.

Project Title	Delineating a role for histone modifications in Down syndrome using human cellular models
Awardee	Broad Institute, Inc.
Project Number
Funding Opportunity Announcement
Summary	This project investigates epigenetic dysregulation in Down syndrome using human induced pluripotent stem cell models to uncover basic mechanisms in Down syndrome that overlap with other neurodevelopmental disorders.

Project Title	Administrative Supplement: A Profile of Spatial Abilities in People with Down Syndrome and Their Correlations with Everyday Behavior
Awardee	Montclair State University
Project Number
Funding Opportunity Announcement
Summary	This diversity supplement will provide training and mentorship for four trainees from underrepresented groups to study spatial abilities in adults with intellectual disabilities, including Down syndrome.

Project Title	Evaluating ASD Symptomatology in Children with Down Syndrome
Awardee	University of Illinois at Urbana-Champaign
Project Number
Funding Opportunity Announcement
Summary	This supplement will contribute to clinical trial readiness by evaluating existing autism spectrum disorder (ASD) measures in a diverse population of 6-18-year-olds with Down syndrome to identify individuals at ASD risk, stratify cohorts by ASD symptom profiles, and monitor response to treatments across these profiles.

Project Title	Determining the neurodevelopmental cell type specific regulatory networks impacted in Down syndrome
Awardee	Seattle Children’s Hospital
Project Number
Funding Opportunity Announcement
Summary	This supplement will integrate existing single-cell RNA-seq and functional multi-omic datasets derived from human brain tissue to identify the cell-type-specific gene regulatory networks altered in the developing Down syndrome brain using high resolution chromatin mapping.

Project Title	Predictors of mortality and of healthy survival in a large community-based prospective cohort of aging adults with Down syndrome
Awardee	University of Nevada, Las Vegas
Project Number
Funding Opportunity Announcement
Summary	This study will use an existing dataset of health outcomes from the longitudinal cohort study Healthy Aging and Intellectual Disability to investigate the modifiable and non-modifiable risk factors for early mortality in Down syndrome.

Project Title	The Impact of Weight Loss on Alzheimer’s Disease Risk in Adults with Down Syndrome
Awardee	University of Kansas Medical Center
Project Number
Funding Opportunity Announcement
Summary	This clinical trial will evaluate the impact of weight loss and diet intake on factors that may prevent or delay the development of Alzheimer's disease in adults with Down syndrome, including biomarkers, cognitive function, cerebral antioxidants, and brain volume.

Project Title	Restoration of proteostasis to address co-occurring conditions in Down Syndrome
Awardee	University of Pennsylvania
Project Number
Funding Opportunity Announcement
Summary	This study will use a mouse model of Down syndrome to test whether disruptions of proteostasis (which maintains balance among the proteins within a cell) can be corrected with the FDA-approved small molecule chaperone 4-phenyl butyrate (PBA) to improve sleep, metabolic, and behavioral deficits in a mouse model of Down syndrome.

Project Title	The role of APP in neurogenesis and AD in Down syndrome
Awardee	University of Illinois at Chicago
Project Number
Funding Opportunity Announcement
Summary	This study will use gene-edited, Down syndrome-derived induced pluripotent stem cells and brain organoids to examine the role of increased expression of the Amyloid Precursor Protein (APP) in neural stem cell proliferation, neuronal differentiation, and the development of Alzheimer’s disease pathology.

Project Title	Why do Down Syndrome patients have high risk of Hirschsprung disease?
Awardee	New York University School of Medicine
Project Number
Funding Opportunity Announcement
Summary	This study will use human genetics, functional genomics in engineered pluripotent stem cells, and mouse models to understand the mechanisms by which chromosome 21 trisomy lead to Hirschsprung disease, an intestinal dysmotility disorder associated with Down syndrome.

Project Title	Mechanistic investigation of therapies for Down Syndrome Regression Disorder
Awardee
Project Number	University of Colorado, Denver
Funding Opportunity Announcement
Summary	This clinical trial will compare the relative safety and efficacy of three alternative therapeutic approaches in Down Syndrome Regression Disorder (DSRD), including two promising immune-modulatory medications.

Project Title	Generation and analysis of new mouse models to determine novel therapeutic targets for Down syndrome-associated cognitive deficits
Awardee	Roswell Park Cancer Institute Corp
Project Number
Funding Opportunity Announcement
Summary	This project will study the characteristics of mouse models of Down syndrome to identify new target genes with therapeutic potential for improving cognitive function and test whether characteristic features of Down syndrome are impacted by the gene-dosage-independent effects of trisomy 21.

Project Title	Novel computational strategies to deconvolute co-occurring conditions in Down syndrome
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This study will develop computational methods to disentangle multi-omic Down syndrome cohort data to reveal the molecular features that drive the spectrum of disease.

Project Title	DEtermining Capacity and Informing Down syndrome Assent Strategies (DECIDAS)
Awardee	University of Arizona
Project Number
Funding Opportunity Announcement
Summary	This study will develop an evidence-based framework to guide the approach to assent for individuals with Down syndrome to participate in clinical trials. The study will determine the capacity of individuals with Down syndrome to provide assent as well as determine the assent-related preferences of parents/legally authorized representatives of children and adults with Down syndrome.

Project Title	Down Syndrome: a potential treatment XISTs
Awardee	Beth Israel Deaconess Medical Center
Project Number
Funding Opportunity Announcement
Summary	This study will investigate whether silencing a third copy of chromosome 21 in a Down syndrome mouse model in vivo can normalize behavioral, neurophysiological, histological, and genetic/epigenetic phenotypes in the mice.

Project Title	Treatment of Obstructive Sleep Apnea with Personalized Surgery in Children with Down Syndrome (TOPS-DS)
Awardee	Oregon Health & Science University
Project Number
Funding Opportunity Announcement
Summary	This clinical trial will compare the effectiveness and outcomes of drug-induced sleep endoscopy, a novel personalized approach to the surgical treatment of obstructive sleep apnea in children with Down syndrome, with adenotonsillectomy (removal of tonsils and adenoids), the current first-line treatment for children with obstructive sleep apnea.

Project Title	Abnormal HIF signaling in Down syndrome-related pulmonary hypertension
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This study will investigate the role of genes that respond to low oxygen levels in a mouse model of Down syndrome to understand why children with Down syndrome are at high risk for developing pulmonary hypertension and other respiratory problems.

Project Title	Randomized Control Trial of oxygen therapy in Children and Adolescents with Down Syndrome and Obstructive Sleep Apnea
Awardee	Cincinnati Children’s Hospital Medical Center
Project Number
Funding Opportunity Announcement
Summary	This clinical trial will test the safety and efficacy of low-flow oxygen treatment in individuals with Down syndrome and moderate to severe obstructive sleep apnea based on the hypothesis that oxygen supplementation will lead to improvements in ventilatory stability, obstructive sleep apnea, cognition, cardiac function, sleep, and quality of life.

Project Title	Dissecting SARS-CoV-2 infection in Down syndrome with congenital heart defects using patient-specific iPSCs
Awardee	Research Institute Nationwide Children’s Hospital
Project Number
Funding Opportunity Announcement
Summary	This study will investigate the genetic causes of the increased susceptibility of individuals with Down syndrome to COVID-19 using patient-specific induced pluripotent stem cells.

Project Title	type I interferon regulates angiogenesis in Down Syndrome ��
Awardee	Lundquist Institute for Biomedical Innovation at Harbor -UCLA Medical Center
Project Number
Funding Opportunity Announcement
Summary	This project will study the role of the hyperactive type I interferon pathway in trisomy 21 on the endothelial cells that line the respiratory tract in the human developing lung as an approach to understand the pulmonary disorders in Down syndrome.

Project Title	Neurovascular unit dysfunction in Down syndrome revealed by TBI
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This study will investigate mild traumatic brain injury (TBI) in mouse models of Down syndrome as an approach to understanding the deficits in the neurovascular unit (neurons, glia, and vascular cells) that may underlie the cognitive and aging issues for those with Down syndrome.

Project Title	A Pilot for Enhancing Support for a Federated Framework of Biospecimens for Down Syndrome Research via the INCLUDE Data Hub
Awardee	Children’s Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	This supplement will support efforts to integrate the Down syndrome-associated biorepositories of the Children’s Hospital of Philadelphia and the Crnic Institute Human Trisome Project with the INCLUDE Data Hub.

Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)-03S2 Supplement
Awardee	University of Pittsburgh at Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This supplement will support the ABC-DS Project’s partnership with a Community Research Advisory Board via an immersion experience and other forms of community outreach in order to enhance recruitment of diverse, underrepresented populations for research on Alzheimer’s disease in Down syndrome.

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Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)-04 Supplement
Awardee	University of Pittsburgh at Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This supplement will support ABC-DS to develop an analytic framework to leverage the complexity and richness of neuroimaging datasets to better understand the trajectory of the brain changes that occur in Alzheimer’s disease in Down syndrome.

Project Title	University of Kansas Alzheimers Disease
Awardee	University of Kansas Medical Center
Project Number
Funding Opportunity Announcement
Summary	This supplement will support the development of a Down Syndrome cohort within the clinical core at the University of Kansas Alzheimer’s Disease Research Center.

Project Title	Down Syndrome: Toward Optimal Trajectories and Health Equity using Medicaid Analytic eXtract (DS -TO-THE-MAX)
Awardee	Boston University Medical Campus
Project Number
Funding Opportunity Announcement
Summary	This supplement will support aN project to collect interpersonal and community level data to describe and examine the impact of specialty care, distance to care, neighborhood characteristics, and Medicaid waivers on health outcomes for adults with Down syndrome.

Project Title	The relationship between language and executive function in DLD and FXS over time
Awardee	University of Wisconsin, Madison
Project Number
Funding Opportunity Announcement
Summary	This supplement will support work to systematically track language production and comprehension over time in school age children with developmental language disorder, fragile X syndrome, or Down syndrome, considering the unique impact of executive function.

Project Title	Early Cognitive Decline in Down Syndrome – Neuroimaging Supplement
Awardee	University of Alabama in Tuscaloosa
Project Number
Funding Opportunity Announcement
Summary	This supplement will support the acquisition of multimodal MRI scans and the quantification of neuroimaging biomarkers of early decline in adolescents and young adults with Down syndrome that may foreshadow the subsequent transition into Alzheimer’s Disease.

Project Title	Elevated mitochondrial fusion and function in Down syndrome - Revision - 2
Awardee	University of Texas Southwestern Medical Center ��
Project Number
Funding Opportunity Announcement
Summary	This supplement will support the development of a model of Down syndrome neuromuscular junctions using induced pluripotent stem cells to determine if elevated metabolic activity increases the cumulative oxidative damage in individuals with Down syndrome.

Project Title	Supplement to TR01 Human cortical development and neural plasticity altered by trisomy 21
Awardee	University of Wisconsin, Madison
Project Number
Funding Opportunity Announcement
Summary	This equipment supplement will fund cell culture-related equipment required to carry out the parent award, specifically two cell culture incubators for maintenance of induced pluripotent stem cells and differentiated neurons and an additional electrophysiological rig for analysis of these neurons.

Project Title	Type I IFN signaling during lung development in Down Syndrome-Multiome sequencing of human fetal and pediatric trisomy 21 lungs
Awardee	Lundquist Institute for Biomedical Innovation at Harbor -UCLA Medical Center
Project Number
Funding Opportunity Announcement
Summary	This supplement will study the development of pulmonary defects in Down Syndrome by using single nuclear RNAseq and multiome sequencing to explore the epigenetic landscape and determine the cellular and molecular abnormalities observed in developing trisomy 21 lungs.

Project Title	Genetic determinants of lymphocyte traits and risk of acute lymphoblastic leukemia in children with Down syndrome
Awardee	University of Southern California
Project Number	1R03HD109778-01
Funding Opportunity Announcement
Summary	This study will examine the role of genetic variation in blood cell traits on the development of Acute Lymphoblastic Leukemia (ALL) in children with Down syndrome and will assess whether blood cell traits are associated with specific features and clinical outcomes in these children.

Project Title	DS-Connect®: The Down Syndrome Registry
Awardee	Leidos, Inc.
Project Number	75N94020F00276
Funding Opportunity Announcement
Summary	Two supplements to this contract will provide upgrades to the Down syndrome patient registry, in order to enhance the professional portal and the registration interface to increase representation and usability.

Project Title	Alzheimer’s Clinical Trials Consortium (ACTC)
Awardee	University of Southern California
Project Number
Funding Opportunity Announcement
Summary	This supplement will allow for a new site to be added to the ACTC network, the Institute Jérôme Lejeune for participation in the NIH INCLUDE Trial-Ready Cohort- Down syndrome (TRC-DS) project, which will enroll adults with Down syndrome in a cohort in preparation for a placebo-controlled clinical trial of an anti-amyloid therapy for Alzheimer’s disease.

Project Title	Defining the Role of DNA Replication of Chromosome 21 in the Development and Pathophysiology of Down Syndrome
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This study will employ a combination of human and mouse culture models and a mouse in vitro fertilization model to define the extent of DNA re-replication errors in response to stress in T21 cells and how this phenomenon could contribute to the development of T21 and other features associated with Down syndrome.

Project Title	Examining COVID-19 in Down Syndrome Patients Using Human iPSC-Derived Organoids
Awardee	Stanford University
Project Number
Funding Opportunity Announcement
Summary	This study will use induced pluripotent stem cells (iPSCs) from individuals with and without Down syndrome and infect them with SARS-CoV-2 virus to investigate how COVID-19 causes myocarditis in cardiac organoids and pulmonary inflammation in lung organoids using single cell RNA sequencing.

Project Title	Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome
Awardee	Children’s Hospital of Los Angeles
Project Number
Funding Opportunity Announcement
Summary	This training award supports a clinician-scientist focused on exploring biomarkers associated with vascular disease, cerebrovascular disease and inflammation in persons with Down syndrome, who are at increased risk of early cerebrovascular disease such as Moyamoya syndrome.

Project Title	Function of RUNX1 in diverse Down syndrome tissues
Awardee	University of Colorado
Project Number
Funding Opportunity Announcement
Summary	This study will explore how the RUNX1 gene found on chromosome 21 contributes to the altered blood cell composition seen in individuals with Down syndrome.

Project Title	Washington University Intellectual and Developmental Disabilities Research Center
Awardee	Washington University
Project Number
Funding Opportunity Announcement
Summary	This award supports part of the Intellectual and Developmental Disabilities (IDD) Research Center at the Washington University School of Medicine, a program that supports IDD-related research; several projects focus on Down syndrome, including one that studies brain development in infants with Down syndrome and another that will generate and characterize new stem cell models of Down Syndrome derived from individuals with the condition.

Project Title	MIND Institute Intellectual and Developmental Disabilities Research Center
Awardee	University of California at Davis
Project Number
Funding Opportunity Announcement
Summary	This award supports a portion of the Intellectual and Developmental Disabilities (IDD) Research Center at the University of California Davis, with a translational science agenda focused on IDDs including Down syndrome; this group is developing validated outcome measures to assess changes in cognitive, behavioral, and language performance as well as studying sleep and ADHD in Down syndrome.

Project Title	District of Columbia Intellectual and Developmental Disabilities Research Center (DC-IDDRC)
Awardee	Children’s Research Institute
Project Number
Funding Opportunity Announcement
Summary	This award supports a portion of the Intellectual and Developmental Disabilities (IDD) Research Center based in the District of Columbia that is creating a translational research environment optimized for studying and defining the basic causes and mechanisms underlying IDDs; one Down syndrome project is focusing on basic neurobiology and another is exploring methods to study executive function in the condition.

Project Title	Waisman Center Intellectual and Developmental Disabilities Research Center
Awardee	University of Wisconsin - Madison
Project Number
Funding Opportunity Announcement
Summary	This award supports portions of the Waisman Center Intellectual and Developmental Disabilities (IDD) Research Center at the University of Wisconsin-Madison, focused on IDD pathology, new interventions, and training the next generation of basic and clinical IDD researchers. Among several Down syndrome projects, several are studying pluripotent stem cells, and others are characterizing aging and dementia in adults or understanding speech and hearing in this population.

Project Title	The Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP/Penn
Awardee	Children’s Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	This award supports part of the Intellectual and Developmental Disabilities (IDD) Research Center at the Children’s Hospital of Philadelphia and the University of Pennsylvania, with the goal of fostering a collaborative, multidisciplinary, cutting-edge community of scientists to develop new neurobiologically-based, patient-centered approaches to therapies for IDD. This center, with a strong Down syndrome clinic, supports projects on cardiometabolic and pulmonary risks in Down syndrome, as well as sleep apnea and endocrine disorders.

Project Title	Down Syndrome: Toward Optimal Trajectories and Health Equity using Medicaid Analytic eXtract (DS -TO-THE-MAX)
Awardee	Boston University Medical Campus
Project Number
Funding Opportunity Announcement
Summary	This project will develop a retrospective cohort of >100,000 adults with and >4,000,000 adults without Down syndrome from 10-years of Medicaid and Medicare data. The study will assess epidemiology and social determinants of obstructive sleep apnea, dementia, and mortality and use machine learning to identify risk algorithms for these co-occurring conditions in a diverse Down syndrome population larger than previous studies.

Project Title	A Human iPSC-Based Chimeric Mouse Model of Alzheimer’s Disease in Down Syndrome
Awardee	Rutgers, The State University of N.J.
Project Number
Funding Opportunity Announcement
Summary	This study will employ a novel human microglial chimeric mouse brain model that is created by transplantation of human Down syndrome induced pluripotent stem cell-derived microglia in mouse brains to study the role of human microglia in the development of Alzheimer’s disease in vivo.

Project Title	Targeting protein synthesis dysregulation in Down syndrome-associated cognitive impairment with aging
Awardee	Wake Forest University Health Sciences
Project Number
Funding Opportunity Announcement
Summary	This study will explore the role of protein synthesis dysregulation in Down syndrome-associated cognitive impairment with aging using mouse models of Down syndrome and electrophysiology, pharmacology, mass spectrometry and proteomics approaches.

Project Title	Mitochondrial inner membrane architecture in skeletal muscle pathophysiology
Awardee	Stanford University
Project Number
Funding Opportunity Announcement
Summary	This supplement will examine the musculoskeletal impact of SARS-CoV-2 (COVID-19) infection in individuals with Down syndrome by studying mitochondrial structure and function in muscle cells from Down syndrome-derived induced pluripotent stem cells (iPSCs) and testing potential drugs to protect against the mitochondrial effects of infection.

Project Title	Understanding the skeleton in Down Syndrome
Awardee	Texas A&M AgriLife Research
Project Number
Funding Opportunity Announcement
Summary	This study aims to understand bone metabolism, turnover, and fracture repair in the setting of Down syndrome. These studies will provide important new insights regarding the specific involvement of genes associated with trisomy 21 and the regulation of skeletal homeostasis in animal models of the condition. The application will provide the first ever detailed molecular assessments of fracture repair in Down syndrome.

Project Title	Human cortical development and neural plasticity altered by trisomy 21
Awardee	University of Wisconsin - Madison
Project Number
Funding Opportunity Announcement
Summary	This study will better define the developmental defects that occur during formation of the human brain in Down syndrome by building a cellular, synaptic, and molecular atlas of the prenatal cortex and by using human induced pluripotent stem cells (iPSCs) to model developmental abnormalities. The results will provide insight into the biological basis of intellectual disability in Down syndrome.

Project Title	Emulating Immune Dysregulation by Trisomy 21 in a Multi-Organ-on-a-Chip System
Awardee	University of Pittsburgh at Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This study will apply organ-on-chip technology to develop physiologically relevant murine and human stem cell-derived models of the lung-bone marrow axis. This study will explore the impact of trisomy 21 on the physiology of the lung, development of immune dysregulation, and mechanisms of exaggerated immune response to inhaled influenza virus.

Project Title	Molecular mechanism of dysregulated airway antiviral responses in children with Trisomy 21
Awardee	Children’s Research Institute
Project Number
Funding Opportunity Announcement
Summary	This study will examine the mechanisms of pathogenesis of severe viral respiratory infections that cause hospitalization and death in children with Down syndrome by evaluating the links between the altered antioxidant response and the immune dysfunction that occur in the airway epithelium in response to viral infection in Down Syndrome.

Project Title	Role of early motor experience in infants with Down syndrome
Awardee	Georgia State University
Project Number
Funding Opportunity Announcement
Summary	This study aims to examine the developmental cascade effects of specific gross and fine motor experiences on motor, cognitive and language development in infants with Down syndrome. This study will test interventions based on a gross motor experience (treadmill stepping) and/or fine motor experience (grasping using “sticky mittens”) to determine their impact on gestures and language production in infants with Down syndrome.

Project Title	COVID and Translational Science supercomputer (CATS)
Awardee	Icahn School of Medicine at Mount Sinai
Project Number
Funding Opportunity Announcement
Summary	This award provides funding support for a portion of a new high-performance supercomputer at Mt. Sinai to be utilized by 46 Principal Investigators engaged in COVID-19-related research and a variety of other translational science applications. Down syndrome projects supported by this supercomputer include studies of aberrant immune response and chromatin regulatory mechanisms as well as COVID-19-related risk factors.

Project Title	Systematic Analysis of 21st Chromosome Ortholog Overexpression in C. elegans
Awardee	University of Texas, Austin
Project Number
Funding Opportunity Announcement
Summary	This award supports a graduate trainee and will examine how the overexpression of each of 51 individual genes on human chromosome 21 conserved in the nematode worm (Caenorhabditis elegans) affects behaviors related to neural or muscular function in this powerful genetic model

Project Title	Precision Medicine for Inflammatory Treatment for Alzheimer's Disease in Down Syndrome
Awardee	University of California, San Diego
Project Number
Funding Opportunity Announcement
Summary	This study will use well-characterized, biobanked plasma samples from the Vitamin E in Down syndrome clinical trial to characterize Alzheimer’s disease biomarkers and develop a precision medicine approach for use of anti-inflammatories in future Down syndrome trials.

Project Title	Type I Interferon Dysregulation in Down Syndrome
Awardee	Icahn School of Medicine at Mount Sinai
Project Number
Funding Opportunity Announcement
Summary	This study will investigate the effects of the presence of additional copies of the interferon receptor genes in Down syndrome, on the interferon response, and the contribution of these extra gene copies to the pathogenesis of inflammatory and immune disorders associated with Down syndrome.

Project Title	A Cognitive Test Battery for Intellectual Disabilities
Awardee	University of California at Davis
Project Number
Funding Opportunity Announcement
Summary	This project will continue to improve the sensitivity of the NIH Toolbox Cognitive Battery (NIHTB-CB) for use as outcome measures in clinical trials for those with intellectual and developmental disabilities (IDD), including Down syndrome, covering domains such as processing speed, memory, cognitive flexibility, attention, and language. This supplement will expand the scope of the battery to include older adults with IDD, as well as those with Down syndrome at risk for dementia, and will collect blood samples for biomarker characterization

Project Title	Energy Expenditure and Weight-Related Behaviors in Youth with Down Syndrome
Awardee	University of Wisconsin Milwaukee
Project Number
Funding Opportunity Announcement
Summary	This study will serve as a template for measuring energy expenditure and providing dietary intake recommendations for youth with Down syndrome, based on a systematic investigation of total daily energy expenditure. In addition, findings will improve understanding of weight-related behaviors (dietary intake, sleep, and activity) as obesity determinants, currently not well understood for this population.

Project Title	Early cognitive decline in Down syndrome - Supplement
Awardee	University of Alabama in Tuscaloosa
Project Number
Funding Opportunity Announcement
Summary	This supplement will fund the collection, banking, and analysis of blood samples from participants with Down syndrome from the parent study, which is examining cognitive function and decline over three years in adolescents and young adults, ages 15-25 years. The goal is to identify which early cognitive changes in adolescents and young adults with Down syndrome are related to blood-based biomarkers of Alzheimer’s disease.

Project Title	Biosignatures of Executive Dysfunction in Down Syndrome
Awardee	Colorado State University
Project Number
Funding Opportunity Announcement
Summary	This supplement aims to identify biosignatures associated with executive dysfunction in children with Down syndrome. Leveraging parent award data collection that includes evaluation of executive function in a cohort of young children with Down syndrome, this project will examine the association between cognitive features and multi-omics findings in the transcriptome, proteome, and metabolome.

Project Title	Tongue maturation deficits in a mouse model of Down syndrome
Awardee	University of Wisconsin – Madison
Project Number
Funding Opportunity Announcement
Summary	This project will investigate abnormalities in oromotor development associated with difficulties in speech, feeding, and swallowing in children with Down syndrome. In this study, investigators will examine early postnatal changes in tongue muscles and brainstem in a mouse model of Down syndrome at three different timepoints during oromotor development, as well as after two different oromotor activity conditions.

Project Title	Elucidating Genotype-Phenotype Relationship of Polygenic Dilated Cardiomyopathies: Administrative Supplement (INCLUDE)
Awardee	Stanford University
Project Number
Funding Opportunity Announcement
Summary	This supplement will study genetic risk factors for congenital heart disease (CHD) in Down syndrome by identifying genetic variants associated with the condition and modeling them in human induced pluripotent stem cells (iPSCs) using gene editing and bioinformatics strategies. Results from this project will uncover the genetic interactions that cause CHD in infants with Down syndrome and provide a valuable sequencing resource and biorepository for the research community.

Project Title	Type I IFN signaling during lung development in Down Syndrome
Awardee	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Project Number
Funding Opportunity Announcement
Summary	This project will study abnormal lung development in Down syndrome by using human fetal lung cultures to define how increased interferon signaling in the developing Down syndrome lung leads to compromised lung development via abnormal cell proliferation and differentiation. This research may ultimately lead to new therapies that target this pathway to overcome hypoplastic lung disease in Down syndrome.

Project Title	Pathological Mechanisms of Human Cerebellar Malformations
Awardee	Seattle Children’s Hospital
Project Number
Funding Opportunity Announcement
Summary	This study aims to define the cellular, molecular and morphological prenatal cerebellar developmental trajectories in human Down Syndrome samples. The generation of developmental profiles through single cell sequencing, histological, and immunohistochemical datasets in model systems of human cerebellar development will elucidate mechanisms of cerebellar hypoplasia in Down syndrome.

Project Title	Capturing and characterizing variability of cognition and behavior in Down syndrome
Awardee	Kaiser Foundation Research Institute
Project Number
Funding Opportunity Announcement
Summary	This study will perform secondary analyses on existing data sets to understand and explain differences in cognition and behavior in people with Down syndrome and explore patterns of genetic variation that may explain some of these differences.

Project Title	Role of endosulfine-alpha expression and phosphorylation in Parkinson's Disease
Awardee	Purdue University
Project Number
Funding Opportunity Announcement
Summary	This study will advance the understanding of how changes in levels of a protein associated with neuronal activity, endosulfine-alpha, or its phosphorylation impact brain function in Down syndrome, thus setting the stage for designing new therapies to improve neurocircuitry defects and alleviate cognitive impairment.

Project Title	Determining the neurodevelopmental cell type specific regulatory networks impacted in Down syndrome
Awardee	Seattle Children’s Hospital
Project Number
Funding Opportunity Announcement
Summary	This study will integrate existing single-cell RNA-sequencing and functional multi-omics datasets derived from human brain samples to identify the cell type-specific gene regulatory networks altered in the developing Down syndrome brain.

Project Title	Predictors of Speech Ability in Children with Down Syndrome
Awardee	Vanderbilt University Medical Center
Project Number
Funding Opportunity Announcement
Summary	This study will measure speech articulation accuracy and speech intelligibility in children with Down syndrome and provide the basis for refining and testing treatments of speech deficits in Down syndrome in future clinical-translational research.

Project Title	Heart and vascular responses across the lifespan in Ts65Dn mice, a model of Down syndrome
Awardee	Syracuse University
Project Number
Funding Opportunity Announcement
Summary	This supplement will investigate the role of chronic exercise on cardiovascular and autonomic function in a mouse model of Down syndrome to address whether lifelong exercise might be a safe and effective intervention for individuals with Down syndrome.

Project Title	Home Sleep Apnea Testing and Neurocognitive Testing for Obstructive Sleep Apnea in Young Adults with Down Syndrome
Awardee	Children’s Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	This supplement will leverage an ongoing study of feasibility, acceptability, and performance of home sleep apnea testing (HSAT) vs overnight in-clinic polysomnography in youth aged 10-20 years with Down syndrome in order to expand enrollment and explore the relationship between obstructive sleep apnea, cognitive function, and cardiometabolic risk factors.

Project Title	Evaluating ASD Symptomatology in Children with Down Syndrome
Awardee	University of Illinois at Urbana-Champaign
Project Number
Funding Opportunity Announcement
Summary	This study contributes to clinical trials readiness by validating existing measures of autism spectrum disorder (ASD) in children with Down syndrome that can be used to screen for ASD risk, stratify cohorts by ASD sub-profiles, and monitor response to treatment. A feasibility study will determine whether a telemedicine-based assessment can be used to evaluate for ASD in children with Down syndrome.

Project Title	Development of an Ecological Momentary Assessment Outcome Measure for Down Syndrome Clinical Trials
Awardee	University of California at Davis
Project Number
Funding Opportunity Announcement
Summary	This study aims to refine and examine the reliability and validity of a technologically innovative, mobile, and respondent-friendly electronic system (iBehavior) for tracking behaviors associated with executive dysfunction in children and adolescents with Down syndrome and other intellectual disabilities.

Project Title	Executive dysfunction as a treatment target for DS clinical trials: An evaluation of its real-world and neural correlates
Awardee	Drexel University
Project Number
Funding Opportunity Announcement
Summary	This study will evaluate executive dysfunction as a treatment target in young adults with Down syndrome and will examine its neural correlates, while linking executive function to adult outcomes important to individuals with Down syndrome and their families, namely vocational status and adaptive behavior skills.

Project Title	Finding the contribution of the autonomic nervous system during perioperative events in children with Down Syndrome
Awardee	Cincinnati Children’s Hospital Medical Center
Project Number
Funding Opportunity Announcement
Summary	Because children with Down syndrome often experience dangerously low heart rates during onset of anesthesia for surgery, this study will characterize the biology of the heart rate control in children with Down syndrome using continuous, non-invasive monitors at home, during perioperative stress, under general anesthesia, and during postoperative pain states.

Project Title	Mobile Diagnosis of Congenital Genetic Conditions: A Model for Screening and Surveillance in Low-Resource Settings
Awardee	Children’s Research Institute
Project Number
Funding Opportunity Announcement
Summary	This study proposes innovative low-cost strategies for reducing the impact of birth defects, based on mobile, facial recognition software to screen for genetic syndromes including Down syndrome, coupled with practical genetic solutions for early diagnosis and monitoring in resource-limited environments such as the Democratic Republic of the Congo (DRC).

Project Title	GM-CSF/sargramostim treatment to improve cognition in Down syndrome
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This study aims to design and complete a clinical trial in adults with Down syndrome using sargramostim (GM-CSF), an FDA-approved drug for increasing the production and differentiation of white blood cells, which has been shown to be safe and improve cognition in animal models of Down syndrome, Alzheimer’s disease (AD), and normal aging, and in human studies of AD and “chemo brain.”

Project Title	Evaluating Assessment and Medication Treatment of ADHD in Children with Down Syndrome
Awardee	Cincinnati Children’s Hospital Medical Center
Project Number
Funding Opportunity Announcement
Summary	This supplement award will enable completion of the first phase of this study, which is characterizing the features of ADHD in children with Down syndrome, and will conduct the first clinical trial of stimulant medication in these children to determine the short- and long-term efficacy and safety of these medications.

Project Title	JAK Inhibition in Down Syndrome
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will enable completion of the first phase of this study, a clinical trial in young adults with Down syndrome and immune skin conditions, using a pharmacological (JAK) inhibitor of interferon signaling.

Project Title	Medications for Obstructive Sleep Apnea to Improve Cognition in Children with Down Syndrome (MOSAIC DS)
Awardee	University of Arizona
Project Number
Funding Opportunity Announcement
Summary	This supplement to this study will enable completion of the initial stages of this clinical trial which will evaluate the combination of two medications, atomoxetine and oxybutynin, as a treatment for obstructive sleep apnea in children with Down syndrome.

Project Title	Predoctoral Training Grant in Pharmacology INCLUDE Down Syndrome Supplement
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement to a training grant will facilitate the education and training of the next generation of graduate students in the discipline of pharmacology who are researching projects specific to Down syndrome and its co-occurring conditions.

Project Title	Predoctoral Training Program in Molecular and Cellular Biology INCLUDE Down Syndrome Supplement
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This training grant supplement aims to train new high-quality graduate students dedicated to pursuing molecular and cellular biology research to enhance our understanding about the causes and potential treatments of Down syndrome.

Project Title	Alzheimer’s Biomarkers Consortium - Down Syndrome (ABC-DS)
Awardee	University of Pittsburgh at Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This project will continue to follow a diverse cohort of adults with Down syndrome to identify amyloid, tau, and other biomarkers of neurodegeneration, as well as risk and resilience factors that modify the development of Alzheimer’s disease in this population to lay the framework for clinical trials.

Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)
Awardee	University of Pittsburgh at Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This equipment supplement will expand quantitative mass spectrometer (MS) capabilities for the Alzheimer’s Biomarkers Consortium – Down Syndrome (ABS-DS) project with a 7500 QTrap® LC-MS/MS system, a next generation triple quadrupole MS, and help to strengthen biomarker discovery, verification, and validation workflows for proposed studies of Alzheimer’s disease in Down syndrome.

Project Title	Alzheimer's Clinical Trials Consortium (ACTC)
Awardee	University of Southern California
Project Number
Funding Opportunity Announcement
Summary	This supplement will allow for a new site to be added to the ACTC network, the Institute Jérôme Lejeune for participation in the NIH INCLUDE Trial-Ready Cohort- Down Syndrome (TRC-DS) project, which will enroll adults with Down syndrome in a cohort in preparation for a placebo-controlled clinical trial of an anti-amyloid therapy for Alzheimer’s disease.

Project Title	Positive Airway Pressure for The Treatment of The Obstructive Sleep Apnea Syndrome In Children With Down Syndrome
Awardee	Children's Hospital of Philadelphia (CHOP)
Project Number
Funding Opportunity Announcement
Summary	This study has now transitioned to the full clinical trial phase, during which participants will be randomized to a 6-month intensive behavioral intervention to improve positive airway pressure (PAP) adherence vs. standard clinical care, and undergo standardized evaluations of behavior, attention, quality of life, and family-relevant outcomes identified during the R61 phase. PAP adherence and health care utilization at baseline, 6, and 12 months will also be measured.

Project Title	Genome Sequencing in support of the Gabriella Miller Kids First Pediatric Research Program
Awardee	Broad Institute, Inc.
Project Number
Funding Opportunity Announcement
Summary	This supplement will support the Kids First Sequencing Center to generate high-quality sequence data, specifically from Down syndrome cohorts funded by INCLUDE, to help build a data resource for the pediatric research community that will be shared through the INCLUDE Data Coordinating Center.

Project Title	Impact of Congenital Heart Disease Surgery on Neurodevelopment and Behavior in Children with Down Syndrome
Awardee	New England Research Institutes, Inc.
Project Number
Funding Opportunity Announcement
Summary	This supplement will expand the age range and methodology to older children (ages 5-7 years) of the original study, which proposed to assess the impact of heart surgery in infancy for complete atrioventricular septal defect on neurodevelopmental and behavioral outcomes at 3-5 years of age in children with Down syndrome.

Project Title	Down Syndrome: A UPDB Discovery Cohort for Translating Genes, Brain and Behaviors to Treatment
Awardee	University of Utah
Project Number
Funding Opportunity Announcement
Summary	This supplement will facilitate recruitment of a large cohort of 200 families, each with a member with Down syndrome, from the unique, multi-generational Utah Population Database (UPDB) that includes >4000 confirmed individuals with Down syndrome. The development of a genomic, pan-omics, and electronic medical record dataset for this Down syndrome cohort and another cohort with deep brain phenotyping will help build and expand the efforts of the INCLUDE Data Coordinating Center.

Project Title	Genome and transcriptome analysis in the Human Trisome Project
Awardee	University of Colorado Denver
Project Number	1X01HD107382-01
Funding Opportunity Announcement
Summary	This award will fund the Kids First Sequencing Center to generate high-quality whole genome sequencing of new samples in the Human Trisome Project (HTP) cohort as well as comprehensive RNA-sequencing of over 600 blood-derived tissue samples in the HTP collection. The HTP is a well-phenotyped cohort of individuals with Down syndrome with multi-omics profiling that will allow evaluation of many of the co-occurring conditions in Down syndrome.

Project Title	Genetic Underpinnings of the Multifactorial Phenotype of Trisomy 21 Patients Unveiled by Multi-Omics Approaches
Awardee	Children's Hospital of Philadelphia (CHOP)
Project Number	1X01HD107379-01
Funding Opportunity Announcement
Summary	This award will fund the Kids First Sequencing Center to provide whole genome sequencing and RNA-sequencing of tissue samples from 777 children with Down syndrome, as well as 321 of their mothers and 148 of their fathers. This racially diverse sample includes detailed phenotypic data from the electronic health records, allowing understanding of the genomic contributors to conditions such as obstructive sleep apnea.

Project Title	The epidemiology of transient leukemia in newborns with Down syndrome
Awardee	University of Southern California
Project Number	1-X01-HD-107380-01
Funding Opportunity Announcement
Summary	This award will fund the Kids First Sequencing Center to generate whole genome sequencing from a long-standing, well-phenotyped collection samples from 470 individuals with Down syndrome and transient abnormal myelopoiesis, a precursor to myeloid leukemia in some children. These data will enrich the INCLUDE Data Coordinating Center as it continues to create a rich resource for future analysis and study.

Project Title	Polyamines in Down syndrome-Alzheimer’s disease
Awardee	University of Denver, Colorado Seminary
Project Number
Funding Opportunity Announcement
Summary	This study will explore whether alterations in polyamine content contribute to the development of Alzheimer’s disease pathology by examining human brain tissue and neuronal cell cultures from Down syndrome mice.

Project Title	Strategies for treatment of Down syndrome: Identifying age- and sex-specific developmental windows using inducible genetic reduction of Dyrk1a
Awardee	Indiana University, Purdue University at Indianapolis
Project Number
Funding Opportunity Announcement
Summary	This study will use both murine and cell-based models to explore the timing and expression of Dyrk1a, a critical gene on chromosome 21, during specific windows of development to determine if there are sex-dependent differences in Down syndrome bone and cognitive phenotypes.

Project Title	Noradrenergic dysfunction in Down syndrome
Awardee	University of Denver, Colorado Seminary
Project Number
Funding Opportunity Announcement
Summary	This study will utilize Designer Receptor (DREADDs) technology to regulate the noradrenergic neurons in the locus coeruleus and evaluate how their loss contributes to neuropathology, vascular changes, and memory loss in mouse models of Down syndrome.

Project Title	Multiplexed Single Nucleus RNA and ATAC-seq Sequencing and Cortical Organoids: Transformative Insights into Down Syndrome
Awardee	University of California, San Diego
Project Number
Funding Opportunity Announcement
Summary	This study will explore neurodevelopment and Alzheimer’s disease pathology through the lens of single nucleus sequencing techniques using brain samples from individuals with Down syndrome, mouse models of Down syndrome, and cortical organoid cultures from induced pluripotent stem cells derived from individuals with Down syndrome.

Project Title	Down syndrome as a systemic autophagy deficiency disorder
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This study will test if deficits in autophagy (cellular recycling) in Down syndrome result in enhanced clonal hematopoiesis that may underlie the increased susceptibility to leukemia and other conditions in people with Down syndrome.

Project Title	Characterizing Innate Immune Dysregulation in Tonsils of Individuals with Down Syndrome
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This study will address how the triplication of the four interferon receptors (IFNAR1, IFNAR2, IFNGR2, and IL-10RB) on chromosome 21 may account for differences in immune cell function in tonsillar tissue obtained from those with Down syndrome and typical control subjects.

Project Title	Discovery of susceptibility genes for Down syndrome-associated congenital heart defects using whole genome sequencing
Awardee	Emory University
Project Number
Funding Opportunity Announcement
Summary	This study will analyze whole genome sequences of individuals with Down syndrome and atrioventricular septal deficits (AVSD), other congenital heart defects, and structurally normal hearts to characterize the genetic contributors and risk factors for AVSD and better understand heart development in Down syndrome.

Project Title	Measuring global, loci-specific RNA degradation to interrogate RNA dysregulation in down syndrome during development
Awardee	University of Colorado
Project Number
Funding Opportunity Announcement
Summary	This study will identify the genes that contribute to comorbidities in individuals with Down syndrome and quantify the degree to which RNA transcription and degradation rates are altered in induced pluripotent stem cells and differentiated neural progenitor cells from individuals with trisomy 21.

Project Title	Systems biology analyses to identify driver genes in Down syndrome-related ALL
Awardee	St. Jude Children’s Research Hospital
Project Number
Funding Opportunity Announcement
Summary	This study will address questions of why children with Down syndrome have an increased risk of acute lymphoblastic leukemia (ALL) and how their leukemia differs from that of children without Down syndrome based on a large genomic profiling project in these individuals.

Project Title	Data Management and Portal for the INCLUDE (DAPI) Project
Awardee	Children’s Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	This project will create a Data Coordinating Center to support investigations of a large cohort of people with Down syndrome for data sharing, data access, and integrative analysis to enable novel investigations into Down syndrome comorbidities across the lifespan.

Project Title	CTSA KL2 Supplement Rebecca Grzadzinski
Awardee	University of North Carolina, Chapel Hill
Project Number
Funding Opportunity Announcement
Summary	This training supplement will characterize longitudinal brain behavior trajectories and developmental profiles from infancy through school-age in children with Down syndrome compared to those with autism spectrum disorder.

Project Title	Translating Measures of Visual Experience to Children with Autism and Down Syndrome
Awardee	Indiana University, Purdue University at Indianapolis
Project Number
Funding Opportunity Announcement
Summary	This training supplement will determine how real-time visual experience within the home learning environment impacts language development for children with developmental delays, including Down syndrome and autism, and whether visual experience can be an outcome measure.

Project Title	Celiac disease signatures in Down syndrome (KL2 Admin Suppl)
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This training supplement will leverage the Human Trisome Project to study the molecular signatures of celiac disease in Down syndrome, and will utilize a pan-omics approach to better understand the pathogenesis and potential biomarkers of celiac disease in those with and without Down syndrome.

Project Title	Vascular Health and Risk Factors in Children with Down Syndrome
Awardee	University of Utah
Project Number
Funding Opportunity Announcement
Summary	This training supplement will determine the prevalence of cardiovascular disease risk factors in children with Down syndrome and evaluate their effect on vascular markers of early atherosclerosis.

Project Title	Down syndrome, early cataracts, eye diseases, and beta-amyloid conformers
Awardee	University of California, San Diego
Project Number
Funding Opportunity Announcement
Summary	Using specially developed nanobodies to different forms of the tau protein, this supplement project will determine the role of tau in retinal and lens tissues of the eye to better understand age-related cataract development and neurodegeneration in Down syndrome.

Project Title	Bronchus-Associated Lymphoid Tissue & Lung Infection in Down Syndrome
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will explore the role of interferon signaling and immune response in bronchus-associated lymphoid tissue and the resulting impact on chronic respiratory tract infection and cognition in a mouse model of Down syndrome.

Project Title	Research Training in Rheumatology INCLUDE Down syndrome Supplement
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This training supplement will support a pediatric rheumatology fellow to investigate idiopathic pulmonary hemorrhage and other acute and chronic autoimmune lung disorders in Down syndrome.

Project Title	Predoctoral Training Grant in Pharmacology INCLUDE Down Syndrome Supplement
Awardee	University of Colorado, Denver
Project Number
Funding Opportunity Announcement
Summary	This project supplement will continue to support three graduate students in a Pharmacology Training Program that will explore the use of chemical and biological agents to affect biological systems and mitigate disease in Down syndrome-related neuroscience.

Project Title	Clinical trials to prevent Alzheimer’s disease in Down syndrome
Awardee	University of Southern California
Project Number
Funding Opportunity Announcement
Summary	This supplement will facilitate new biomarker assays on spinal fluid and blood samples as well as Tau PET imaging for participants in the Trial-Ready Cohort of adults with DS (TRC-DS) project in advance of a randomized, placebo-controlled clinical trial for Alzheimer’s disease in Down syndrome.

Project Title	Role of SARS-CoV-2 mediated type I IFN antagonism in individuals with Down syndrome
Awardee	Icahn School of Medicine at Mount Sinai
Project Number
Funding Opportunity Announcement
Summary	This supplement will study the functional significance of the increased dose of type I interferon receptors in cells from individuals with Down syndrome to determine their response to infection with SARS-CoV-2 causing COVID-19.

Project Title	Pre-clinical assessment of JAK inhibitors to ameliorate cytokine storms in Down syndrome
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will test the ability of FDA-approved Janus Kinase (JAK) inhibitors to rescue the “cytokine storm” and multi-organ inflammation in a mouse model of Down syndrome that shares many properties with the immune hypersensitivity that can occur in SARS-Co-V-2/COVID-19 infection.

Project Title	Impact of COVID-19 on the Mental Health of People with Down Syndrome
Awardee	Virginia Commonwealth University
Project Number
Funding Opportunity Announcement
Summary	This supplement will examine the impact of COVID-19 pandemic-related stressors on the health and well-being of caregivers and people with Down syndrome.

Project Title	Interferon hyperactivity, COVID-19, and Down syndrome
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This supplement will investigate the interplay between interferon hyperactivity, immune dysregulation, COVID-19 pathology, and immunity against SARS-CoV-2 by studying the clinical and immunological characteristics of COVID-19 in Down syndrome.

Project Title	IFN responses and SARS-CoV-2 Receptor ACE2 Expression in the airway epithelium of young children with Down Syndrome
Awardee	Children’s Research Institute
Project Number
Funding Opportunity Announcement
Summary	This supplement will investigate the interferon-driven antiviral and pro-inflammatory responses in airway epithelial cells obtained from young children with Down syndrome to better understand susceptibility to COVID-19 infection.

Project Title	The Role of Inflammation and NGF Dysfunction in the Evolution of Alzheimer Disease Pathology in Down Syndrome-Supplement
Awardee	University of California-Irvine
Project Number
Funding Opportunity Announcement
Summary	This supplement will incorporate additional inflammatory, Alzheimer’s disease (AD)-related, and neurodegeneration biomarkers in studies of people with Down syndrome and in Down syndrome tissues to study the exposure and severity of COVID-19 infection in trisomy 21.

Project Title	Genetic-epigenetic and aging interactions at COVID-19 host response loci in Down syndrome and mouse models
Awardee	Hackensack University Medical Center
Project Number
Funding Opportunity Announcement
Summary	This supplement will use both human samples and a mouse genetic model of COVID-19 susceptibility that will be generated to understand how host responses to the SARS-CoV-2 virus might differ in individuals with Down syndrome based on DNA methylation differences.

Project Title	Early Cognitive Decline in Down Syndrome
Awardee	University of Alabama in Tuscaloosa
Project Number
Funding Opportunity Announcement
Summary	This project seeks to identify domains of very early cognitive and motor decline prior to overt symptoms of cognitive impairment in youth with Down syndrome ages 15-25 years using a battery of neuropsychological and behavioral measures over three years.

Project Title	Enabling self-reported outcomes for youth with developmental disabilities: The Pediatric Evaluation of Disability Inventory - Patient Reported Outcome (PEDI-PRO) - Phase II
Awardee	Ablelink Technologies, Inc.
Project Number
Funding Opportunity Announcement
Summary	This Phase II small business award will build a clinically robust assessment software tool called PEDI-PRO to address the gaps in patient-reported outcome measures (PROMs) of functional abilities in youth aged 14-22 years with developmental disabilities, including Down syndrome.

Project Title	Heart and vascular responses across the lifespan in Ts65Dn mice, a model of Down syndrome
Awardee	Syracuse University
Project Number
Funding Opportunity Announcement
Summary	This study will examine cardiovascular changes, including blood pressure, vascular tone, and endothelial function, related to age and sex in a mouse model of Down syndrome.

Project Title	Preventing cognitive impairment in mouse genetic models of Down syndrome by early postnatal suppression of Kir3.2 channel signaling
Awardee	University of California, San Diego
Project Number
Funding Opportunity Announcement
Summary	This study will examine the effects of increased dosage of the Kcnj6 gene (encoding a potassium channel) on neural circuits and cognitive impairment in a mouse model of Down syndrome.

Project Title	Development and treatment of skeletal deficits in a Down syndrome mouse model
Awardee	Indiana University, Purdue University at Indianapolis
Project Number
Funding Opportunity Announcement
Summary	This project will evaluate differences in skeletal deficits between adolescent male and female mouse models of Down syndrome, determine the cellular basis for these differences, and explore the role of the trisomic Dyrk1a gene in these bone abnormalities.

Project Title	Dissecting the role of FMRP in RNA processing using human stem cell models
Awardee	Broad Institute, Inc.
Project Number
Funding Opportunity Announcement
Summary	This project will investigate the molecular mechanisms underlying the association between the RNA-binding protein, FMRP (whose loss causes Fragile X syndrome) and its RNA targets transcribed from chromosome 21, with the goal of understanding RNA processing deficits in both Down syndrome and Fragile X syndrome.

Project Title	Beyond Gene Dosage: Understanding Down Syndrome via 4D Genome Organization
Awardee	University of Texas at Houston, Health Science Center
Project Number
Funding Opportunity Announcement
Summary	This project will test the hypothesis that trisomy 21 deregulates the 3-dimensional genome and broadly impacts gene expression in Down syndrome cells by forming abnormal interactions between chromosomes through the use of epigenomic, transcriptomic, optogenetic and other techniques.

Project Title	Lifestyle and Alzheimer’s Disease In Down Syndrome
Awardee	University of Wisconsin–Madison
Project Number
Funding Opportunity Announcement
Summary	This study will investigate the longitudinal associations of lifestyle factors (physical activity, sleep, cognitive stimulation, and social engagement) on early Alzheimer’s disease neuropathology, cognitive functioning, and dementia symptoms in adults with Down syndrome.

Project Title	Effects of Hypoglossal Nerve Stimulation on Cognition & Language in Down Syndrome
Awardee	Massachusetts Eye and Ear Infirmary
Project Number
Funding Opportunity Announcement
Summary	This clinical trial will test the effects of hypoglossal nerve stimulation treatment of obstructive sleep apnea (OSA) on neurocognition and expressive language in children and adolescents with Down syndrome.

Project Title	Exploring the role of gonadotropins in Down syndrome
Awardee	University of North Texas Health Science Center
Project Number
Funding Opportunity Announcement
Summary	This study will evaluate the role of gonadotropins and other factors to better understand the mechanisms underlying the ocular condition, keratoconus, that is common in the Down syndrome population.

Project Title	Molecular Mechanisms of Defective Oligodendrocyte Differentiation in Down Syndrome
Awardee	Boston University Medical Campus
Project Number
Funding Opportunity Announcement
Summary	Using trisomic induced pluripotent stem cell lines, this doctoral candidate will explore the molecular basis of altered oligodendrocyte development that may contribute to white matter abnormalities in the brain of individuals with Down syndrome.

Project Title	Neural basis of locomotor dysfunction in Down syndrome
Awardee	Children’s Research Institute
Project Number
Funding Opportunity Announcement
Summary	This project will identify specific alterations in the Purkinje cell circuitry of the cerebellum that result in locomotor and gait abnormalities in a mouse model of Down syndrome.

Project Title	A Cognitive Test Battery for Intellectual Disabilities
Awardee	University of California, Davis
Project Number
Funding Opportunity Announcement
Summary	This project will fulfill knowledge gaps in the NIH Toolbox Cognitive Battery by completing development and validation of new tests for those with moderate and severe intellectual and developmental disabilities (IDD), including Down syndrome, and test its sensitivity to detect treatment-related changes in a trial of methylphenidate in children and adolescents with IDD and ADHD.

Project Title	RAT21: Generation and Characterization of Rat Models of Down Syndrome
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This project will develop and characterize rat models of Down syndrome on several strain backgrounds.

Project Title	Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)
Awardee	University of Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This project will continue to follow a cohort of adults with Down syndrome to identify amyloid, tau, and other biomarkers of neurodegeneration, as well as risk and resilience factors that modify the development of Alzheimer’s disease in this population to lay the framework for clinical trials.

Project Title	Molecular epidemiology of acute lymphoblastic leukemia in children with Down syndrome
Awardee	Baylor College of Medicine
Project Number
Funding Opportunity Announcement
Summary	This study aims to determine the basis for the increased risk of acute lymphoblastic leukemia in children with Down syndrome by analyzing the genetic and genomic variants associated with leukemia and identifying the impact of Down syndrome-related phenotypes on leukemia susceptibility and outcomes.

Project Title	Data Coordinating Center for the Pediatric Heart Network
Awardee	New England Research Institutes, Inc.
Project Number
Funding Opportunity Announcement
Summary	This award will add training in caring for individuals with Down syndrome for physicians in the Pediatric Heart Network.

Project Title	A Longitudinal MRI Study Characterizing Very Early Brain Development in Infants with Down Syndrome
Awardee	Washington University
Project Number
Funding Opportunity Announcement
Summary	This project will create a cohort of infants with Down syndrome, data from which can be used to address recommendations for investigation of comorbid autism, characterize cardiovascular and other potential physical health characteristic, and conduct future biospecimen analyses, including genetic analyses.

Project Title	Type I Interferon Dysregulation in Down Syndrome
Awardee	Icahn School of Medicine At Mount Sinai
Project Number
Funding Opportunity Announcement
Summary	This study will provide mechanistic insights on the molecular regulation of IFN-1 in DS, and may ultimately lead to a therapeutic strategy to alleviate DS-associated immune disorders.

Project Title	Understanding Down Syndrome as an Interferonopathy
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This project will research the immune disorders in Down syndrome and provide mechanistic insights on the effects of Down syndrome on hyperactive interferon (IFN) signaling and associated phenotype.

Project Title	Research Training in Rheumatology
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This program provides professional development to a Pediatric Rheumatology trainee to conduct research to advance medical knowledge of rheumatic and autoimmune diseases in individuals with Down syndrome.

Project Title	University of Colorado Cancer Center Support Grant
Awardee	University of Colorado Cancer Center
Project Number
Funding Opportunity Announcement
Summary	This project will form a research team who will use human samples obtained from an ongoing pan-omics cohort study of people with DS and novel mouse models of DS carrying varying copy numbers of the IFNR gene cluster to define the role of IFNR triplication and hyperactive IFN signaling on: 1) Clonal expansion of leukemogenic mutations in the hematopoietic compartment; 2) Increased toxicity during chemotherapy for pediatric leukemias.

Project Title	Susceptibility to and Release from Masking in Infancy and Childhood
Awardee	Father Flanagan's Boys' Home
Project Number
Funding Opportunity Announcement
Summary	This supplement supports an existing grant that will enroll 60 school-age children with Down syndrome (5-17 years) in order to evaluate their speech recognition in the context of each child’s hearing function, cognitive functioning, medical history, parent questionnaires and language measures.

Project Title	Down syndrome, early cataracts, eye diseases, and beta-amyloid conformers
Awardee	University of California, San Diego
Project Number
Funding Opportunity Announcement
Summary	This study will develop novel nanoantibodies against the multiple conformers of beta-amyloid (Aβ) and use these to study the development of plaques in the eyes of Alzheimer’s Diseases mouse models.

Project Title	Predoctoral Training Grant in Pharmacology
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This project will support a Pharmacology Training Program that will study how the use of chemical and biological agents can affect biological systems and mitigate disease in Down syndrome-related neuroscience.

Project Title	Trisomy 21 and RNA polymerase II function
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This research will investigate the role of global RNA polymerase II (pol II) dysregulation in Down syndrome.

Project Title	JAK Inhibition in Down Syndrome
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This research will evaluate the safety and therapeutic effects of tofacitinib, an agent which targets JAK signaling, on immune-mediated dermatological conditions in young adults with Down syndrome.

Project Title	Evaluating outcome measures in young adults with Down syndrome
Awardee	Cincinnati Children’s Hospital Medical Center
Project Number
Funding Opportunity Announcement
Summary	This supplement will extend the evaluation of psychometric properties of recommended promising measures of cognitive outcomes to young adults with Down syndrome (ranging from 18-29 years of age). The parent grant is evaluating the outcome measures in school aged children.

Project Title	Elevated mitochondrial fusion and function in Down syndrome
Awardee	The University of Texas Southwestern Medical Center
Project Number
Funding Opportunity Announcement
Summary	This research will study mitochondrial metabolism and oxidative stress in Down syndrome, and may ultimately lead to the identification of dominant genes associated with the DS phenotype.

Project Title	Acceptability and Performance on In-Home Polysomnography in Youth with Down Syndrome
Awardee	Children's Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	This research will develop and test the feasibility and accuracy of a home-based sleep assessment tool in diagnosing Obstructive sleep apnea syndrome (OSAS) in adolescents with Down syndrome.

Project Title	fNIRS as an outcome measure of the prefrontal hemodynamic response in Down syndrome
Awardee	Drexel University
Project Number
Funding Opportunity Announcement
Summary	This research will test the feasibility of using functional near infrared spectroscopy (fNIRS) and executive functioning neurodevelopmental tests in individuals with Down syndrome.

Project Title	Evaluating Assessment and Medication Treatment of ADHD in Children with Down Syndrome
Awardee	Cincinnati Children’s Hospital Medical Center
Project Number
Funding Opportunity Announcement
Summary	This research will determine the phenotypic characteristics differentiating children with comorbid Down syndrome and ADHD from those with Down syndrome alone, and to conduct a randomized controlled trial of stimulant medication in the Down syndrome + ADHD group.

Project Title	Washington University Intellectual and Developmental Disabilities Research Center
Awardee	Washington University
Project Number
Funding Opportunity Announcement
Summary	This project will build a patient-derived induced pluripotent stem cell (iPSC) resource from DS individuals and explore molecular and cellular signatures from differentiated cortical interneurons that reflect different cognitive abilities of the donors.

Project Title	Kansas Intellectual and Developmental Disabilities Research Center
Awardee	University of Kansas Lawrence
Project Number
Funding Opportunity Announcement
Summary	This project will 1) increase DS-Connect® registry enrollment, 2) extract clinical observations, treatments, and outcomes from PCORnet, the �����鶹��Ƶ Patient-Centered Clinical Research Network, for DS-Connect subjects, and 3) conduct on-line cognitive assessments (Self-Determination Inventory, SDI) via DS-Connect in the PCORnet population and link to data on obstructive sleep apnea as proof of principle.

Project Title	Positive Airway Pressure for the Treatment of the Obstructive Sleep Apnea Syndrome in Children with Down Syndrome
Awardee	Children's Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	This study will evaluate interventions to enhance CPAP adherence in children/adolescents with Down syndrome and comorbid obstructive sleep apnea (OSA).

Project Title	Data Coordinating Center for the Pediatric Heart Network
Awardee	New England Research Institutes, Inc.
Project Number
Funding Opportunity Announcement
Summary	This supplement will assess the impact of congenital heart disease (CHD) repair on neurodevelopmental (ND) and behavioral outcomes at 3-5 years of age by comparing Down syndrome children with heart surgery repair to age-matched Down syndrome controls without CHD.

Project Title	Identifying Measures of Pulmonary Morbidity for Clinical Trials in Children with Down Syndrome and Aspiration
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	The project will conduct a case-controlled study to determine the pulmonary factors that may significantly contribute to morbidity and mortality in patients with Down syndrome, with a focus on chronic aspiration.

Project Title	Medications for Obstructive Sleep Apnea to Improve Cognition in Children with Down Syndrome (MOSAIC DS)
Awardee	University of Arizona
Project Number
Funding Opportunity Announcement
Summary	This research will conduct a trial of combined atomoxetine and oxybutynin (ato-oxy) medication, a regimen to improve airway tone which has proven effective in adults with obstructive sleep apnea (OSA), in children with Down syndrome.

Project Title	Innovation through collaboration at the intersection of childhood development and cancer: a platform for the Gabriella Miller Kids First Pediatric Data Resource Center
Awardee	Children's Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	The project will incorporate approximately 2,000 existing DNA samples collected from individuals with Down syndrome into The Kids First Data Resource Center (DRC), a repository of whole-genome sequence and clinical data from childhood cancer and structural birth defects patient cohorts.

Project Title	Cardiovascular Biomechanics and Imaging in Down syndrome
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	The project will incorporate approximately 2,000 existing DNA samples collected from individuals with Down syndrome into The Kids First Data Resource Center (DRC), a repository of whole-genome sequence and clinical data from childhood cancer and structural birth defects patient cohorts.

Project Title	Academic Training Program in Pediatric Pulmonary Disease
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	The project will expand an existing postdoctoral training program in pediatric pulmonary disease to include a novel interdisciplinary training program with a focus on cardiopulmonary disorders related to Down syndrome.

Project Title	Epigenetic Silencing of HSA21 in Down Syndrome
Awardee	Beth Israel Deaconess Medical Center
Project Number
Funding Opportunity Announcement
Summary	This study will investigate the development of neurons and astrocytes in cortical organoid cultures derived from Down syndrome patient iPSCs, assess the impact of HSA21 by using an Xist strategy to silence HSA21 in Down syndrome patient iPSCs, and examine mouse models to track cell type specific transcriptomic changes and gene expression abnormalities over the animal’s lifespan.

Project Title	University of Pittsburgh Clinical and Translational Science Institute
Awardee	University of Pittsburgh At Pittsburgh
Project Number
Funding Opportunity Announcement
Summary	This project will develop culturally and linguistically appropriate educational and recruitment materials related to participation in Down syndrome research for African Americans with Down syndrome, their families and, caregivers, and increase recruitment of individuals with Down syndrome into related studies in the clinical trial portal .

Project Title	ITM 2.0: Advancing Translational Science in Metropolitan Chicago
Awardee	University of Chicago
Project Number
Funding Opportunity Announcement
Summary	Using large clinical data sets this project will characterize unique comorbidity patterns in people with Down syndome, discover disease subtypes in the syndrome and develop predictive health / life trajectories of these subtypes. This project will provide the ability to stratify cohorts to enable clinical trial recruitment to be more expeditiously and accurately conducted.

Project Title	Clinical trials to prevent Alzheimer’s Disease in Down Syndrome
Awardee	University of Southern California
Project Number
Funding Opportunity Announcement
Summary	This project will develop a ‘trial-ready’ cohort of middle-aged amyloid-positive individuals with Down Syndrome (DS) and then, in Phase II, conduct a trial of an anti-amyloid therapeutic agent.

Project Title	Evaluation of myocardial targets to prevent anthracycline cardiotoxicity in children with Down Syndrome and Leukemia
Awardee	State University of New York At Buffalo
Project Number
Funding Opportunity Announcement
Summary	This research will investigate the role of the DYRK1ASRp55-TNNT2 pathway during anthracycline cardiotoxicity in a model of beating cardiomyocytes with trisomy 21, examine whether combined pharmacological inhibition of CBR1 and DYRK1A activities are able to protect trisomic cardiomyocytes from the cardiotoxic effects of anticancer anthracyclines, and study the extent of genome-wide splicing alterations linked to the increased expression of the master splicing factor SRp55 in myocardial tissue from persons with Down syndrome.

Project Title	Predoctoral Training Program in Molecular Biology
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This will support training new high-quality scientists dedicated to pursuing biomedical research to enhance understanding about the causes and potential treatments of Down syndrome.

Project Title	Epigenetics of Down Syndrome
Awardee	Hackensack University Medical Center
Project Number
Funding Opportunity Announcement
Summary	This research will quantitatively analyze age-related immune system alterations, epigenetic changes, loss of hearing, cognitive decline and behavioral changes in three different Down syndrome mouse models with segmental duplications.

Project Title	Intellectual and Developmental Disabilities Research Centers 2013
Awardee	Hugo W. Moser Research Institute at Kennedy Krieger
Project Number
Funding Opportunity Announcement
Summary	This research will validate a behavioral measure of executive function (EF) as a resource for future clinical trials for interventions in Down syndrome.

Project Title	Early risk for ADHD symptoms in young children with Down syndrome
Awardee	Colorado State University
Project Number
Funding Opportunity Announcement
Summary	This study will conduct a retrospective analysis to evaluate associations between infant cognitive control and the presentation of Attention Deficit and Hyperactivity Disorder (ADHD) symptoms at ages 4-5.

Project Title	Waisman Intellectual and Developmental Disabilities Research Center
Awardee	University of Wisconsin-Madison
Project Number
Funding Opportunity Announcement
Summary	This project will build an under-18 year old DS cohort, performing comprehensive clinical, neurobehavioral, and ‘omics research on this population, to prepare them for future studies and clinical trials

Project Title	Ancestral roles of histone-modifying genes in heart development and disease
Awardee	Children’s Research Institute
Project Number
Funding Opportunity Announcement
Summary	This research will test the hypothesis that congenital heart disease in Down syndrome is caused by dysregulation of autophagic signaling in specific gene populations.

Project Title	Understanding the complexity of gene dosage imbalance in Down syndrome
Awardee	Children's Hospital of Philadelphia
Project Number
Funding Opportunity Announcement
Summary	This research will investigate the gene dosage imbalance in Down syndrome, and potentially provide a well-defined set of isogenic DS induced pluripotent stem cells (iPSCs) to probe the effects of trisomy 21 (T21) on genome-wide transcriptome and chromatin architecture.

Project Title	Human iPSC Model for Elucidating Crosstalk Signaling and Secretomes: Down Syndrome Administrative Supplement
Awardee	Stanford University
Project Number
Funding Opportunity Announcement
Summary	This research assess whether overexpression of cardiac-specific, dosage-sensitive trisomic genes on chr21 leads to heart defects through impaired cardiac crosstalk and myocyte maturation.

Project Title	Bronchus-Associated Lymphoid Tissue & Lung Infection in Down Syndrome
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	This research will test whether lower levels of Bronchus-associated lymphoid tissue (BALT), which controls a variety of immune and inflammatory responses, leads to increased respiratory tract infections (RTI) in patients with Down syndrome.

Project Title	Molecular Causes of Down Syndrome Associated Congenital Heart Disease and Other Phenotypes
Awardee	Harvard Medical School
Project Number
Funding Opportunity Announcement
Summary	This project will use state of the art genomics technologies to identify genetic mechanisms for Down syndrome phenotypes.

Project Title	Clinical and Translational Science Award
Awardee	Columbia University Health Sciences
Project Number
Funding Opportunity Announcement
Summary	The project will reprogram established fibroblast lines from older DS subjects with and without concomitant AD into induced pluripotent stem cells (iPSCs) and then differentiate these iPSCs into neurons and then into cortical organoids (mixed cortical neuron and astrocyte 3D culture). These organoids will be used to perform transcriptomic analysis and to examine differences in neuronal development and function.

Project Title	Accelerating Clinical Research on Down Syndrome at the CCTSI and Beyond
Awardee	University of Colorado Denver
Project Number
Funding Opportunity Announcement
Summary	The project will complete the pan-omics analysis of a cohort of patients with Down syndrome and controls, and allow investigators to complete abstraction of demographics and clinical data and generation of key -omics datasets for 300 participants (200 DS and 100 Age/gender matched controls) already enrolled in the Crnic Institute’s Human Trisome Project (HTP) Biobank.

Project Type	New Projects within Current Research
Awardees
Summary	These supplements support research to improve the understanding of the biology of Down syndrome and to development new treatments for health conditions experienced by individuals with Down syndrome.

Project Type	New Projects within Current Research
Awardees
Summary	These supplements support research focused on connecting large study populations, or cohorts, of individuals with Down syndrome, and enrolling new participants at different ages. Data collected with this research will contribute to a better understanding of the full range of conditions experienced with individuals with Down syndrome across the lifespan.

Project Type	New Projects within Current Research
Awardees
Summary	These supplements support efforts to identify existing clinical trials that seek to address conditions common in individuals with Down syndrome to bolster recruitment and inclusion in more clinical studies across multiple clinical sites.

Notice	Notice of Special Interest (NOSI): Availability of Administrative Supplements for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project
Notice Number
Release Date	December 18, 2019
Application Due Date(s)	March 23, 2021; March 23, 2022
Expiration Date	March 24, 2022

Notice	Notice of Special Interest: Mentored Career Development Awards to Foster the Careers of Investigators Pursuing Research Related to Down syndrome as Part of the INCLUDE Project
Notice Number
Release Date	December 6, 2019
Application Due Date(s)	February 12, 2021; June 12, 2021; October 12, 2021
Expiration Date	January 8, 2022

Notice	Notice of Special Interest: Ruth L. Kirschstein �����鶹��Ƶ Research Service Award (NRSA) Fellowship Awards to Support Training in Research Related to Down Syndrome as Part of the INCLUDE Project
Notice Number
Release Date	December 6, 2019
Application Due Date(s)	April 8, 2021; August 8, 2021; December 8, 2021
Expiration Date	January 8, 2022

Notice	Notice of Special Interest (NOSI): NIH Research Project Grants on Down Syndrome (R01) for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project
Notice Number
Release Date	December 18, 2019
Application Due Date(s)	February 5, 2021; June 5, 2021; October 5, 2021
Expiration Date	January 8, 2022

• Evaluation of the genetic, epigenetic, and epidemiologic factors associated with trisomy 21 that lead to greatly increased risk of childhood leukemias and that lead to the distinctive biological and clinical behavior of these leukemias.
• Evaluation of the genetic, epigenetic, and epidemiologic factors associated with trisomy 21 that lead to reduced risk for selected childhood and adult solid tumors.
• Characterization of the biological and clinical factors that drive the development of transient abnormal myelopoiesis (TAM) and its progression to acute myeloid leukemia (AML) in children with trisomy 21.
• Mining and/or generation of -omics datasets of clinically annotated specimens of Down syndrome acute lymphoblastic leukemia (ALL) and AML.
• Translational research associated with completed/ongoing clinical trials to identify prognostic factors (e.g., minimal residual disease) that can be used to reliably guide treatment for children with leukemia associated with Down syndrome.

• Examining the potential to further the understanding of ocular pathologies frequently seen in Down syndrome (manifestations that include, but are not limited to, cataract, amblyopia, strabismus and refractive errors).
• Examining the regulation or dysregulation of eye development in Down syndrome are also encouraged. Interested applicants are advised to contact the NEI program officer prior to submitting an application.

• Incorporation of individuals with Down syndrome into disease cohorts and clinical trials directed toward sleep apnea, congenital heart disease, pediatric pulmonary hypertension, and adult cardiovascular disease. This could include collection of tissue or blood specimens and –‘omics data generation and analysis (genomics, transcriptomics, metabolomics, etc.), imaging, computational modeling, or expansion of a clinical trial to include a number of Down syndrome cases necessary to provide sufficient statistical power for stratification. Studies are encouraged to leverage the DS-Connect® registry to identify potential participants.
• Mining and/or generation of -omics datasets of heart, lung, blood, and sleep disorders for functions of genes on chromosome 21 or downstream of genes on chromosome 21.
• Characterization in animal models of the morphological events occurring in early heart development that give rise to the specific forms of congenital heart disease that are the primary cause of death during the first year of life for infants born with Down syndrome.
• Characterization of differentiation of disease-related tissue types in induced pluripotent stem cells (iPSCs) derived from cells from individuals with Down syndrome and compared to euploid iPSCs.
• Identification of potential risk and resilience factors that make individuals with Down syndrome susceptible to transient or persistent blood disorders and congenital heart disease but protected from adult cardiovascular disease.

• Examining ethical, legal and social implications (ELSI) related to preimplantation and prenatal screening and testing for trisomy 21.
• Studying how Down syndrome is understood by individuals, families, and specific subgroups within society.
• Promote research to advance the application of genomics to medical science and clinical care of Down syndrome patients.
• Promote basic genomics research and technology development for the function of trisomy 21.

• Understanding the molecular mechanism underlying the interplay between aging and neurodegeneration in Down syndrome through (epidemiologic, genomic, and mechanistic studies), as well as examining mechanisms of resilience in Down syndrome individuals who remain free of dementia in the face of Alzheimer’s pathology. Of particular interest are studies generating and making available high-quality ‘omics’ data that can be used for downstream systems biology and other predictive modeling efforts.
• Identification of sensitive neuropsychological measures of cognitive decline, imaging, blood-based, and genetic biomarkers associated with transition from normal aging to mild cognitive impairment to clinical dementia in adults with Down syndrome, as well as improved measures of quality of life.
• Development of new technologies to help persons aging with Down syndrome.
• Development of interventions to improve health, function, social engagement, productivity and quality of life of persons aging with Down syndrome, and to reduce risks for aging-related chronic diseases including dementia.
• Developing comparative studies of treatments, care plans and standardized care follow-up (similarly to those now operational in younger patients with Down syndrome) that could support better comorbidity management and health and well-being in the aging Down syndrome population.
• Analysis of national trends and trajectories in physical and cognitive health (including Alzheimer’s/dementia) and function in the population of persons aging with Down syndrome, including disparities by race/ethnicity, gender and socioeconomic status.
• Research that addresses the unique challenges related to the provision of care by families for adults with Down syndrome, including development of interventions to support family caregivers.

• Examination of immune system dysregulation in Down syndrome; its molecular basis, impact on health, including infections and autoimmunity, and intervention strategies.

• Basic science studying chromosome silencing; white matter and brain development; gene therapy or prenatal therapy in animal models of Down syndrome to ameliorate the effects of trisomic gene dosage; studies of rodent models to understand cognition, behavior, and other aspects of the phenotype across different stages of development; development of novel tools for understanding the basic biology of Down syndrome, such as well-characterized induced pluripotent cell lines, cell and tissue repositories, new murine and other rodent models that can better replicate the chromosome regions syntenic to human chromosome 21 as well as reproduce the complex neurobehavioral and other phenotypic features of Down syndrome; and mechanisms to link to current model organism databases and resources.
• Increasing the pool of individuals with Down syndrome for cohort studies, deep phenotyping, biospecimen collection, 'omics studies, and ultimately, clinical trials, such as through enhancements to recruitment, phenotyping services, and biobanks as well as pan-'omics approaches in readily available cohorts; strategies to recruit individuals from underrepresented racial and ethnic minorities as well as IDeA (Institutional Development Award) states with limited NIH funding to ensure representation from rural and medically underserved areas; approaches that capture the priorities of parents and individuals with Down syndrome; studies that facilitate linkages between pan-'omics data sets, patient-reported outcomes, electronic medical records, and DS-Connect® () to facilitate data sharing, data mining, and secondary uses; development and validation of sensitive, robust, and reproducible outcome measures for complex phenotypes such as cognition and behavior using tools such as the NIH ToolBox that can be used in clinical trials; studies to expand and extend the available biomarkers for studies of regression, aging, and dementia in adolescents and adults with Down syndrome; approaches that characterize developmental trajectories at transitional life stages for those with Down syndrome such as infant to child and adolescent to adult; and studies of risk and resilience for co-occurring conditions in Down syndrome.
• Adding or expanding a Down syndrome component to an existing pharmacologic clinical trial for a condition common in Down syndrome but for which dosage and/or efficacy have not been established in this population; proposals that focus on clinical trial readiness to facilitate future clinical trials in those with Down syndrome such as through focused natural history studies or biomarker or clinical outcome assessment development; additions to existing clinical trial networks to establish the infrastructure necessary for clinical trials in those with Down syndrome, including efforts to link to existing datasets and add participants to DS-Connect®; studies to develop new therapeutics and interventions for people with Down syndrome; clinical trials in individuals with Down syndrome to treat co-occurring conditions such as sleep apnea, epilepsy, developmental regression, or others; and studies that explore the ethical, legal, and social implications of research on populations with reduced decisional capacity and optimal methods for obtaining informed consent in those with Down syndrome.

• Examining arthritic (and other rheumatic), musculoskeletal, and skin anomalies and disorders in Down syndrome, and causes, treatment and prevention of arthritic (and other rheumatic), musculoskeletal, and skin complications throughout the lifespan in individuals with Down syndrome.

• Improving understanding of the natural history of communication disorders (hearing, balance/vestibular, voice, speech, language, taste and smell) throughout the lifespan in Down syndrome.
• Early identification and clinical management of communication disorders throughout the lifespan in individuals with Down syndrome.

• Evaluating genetic, molecular, or epidemiologic factors that are associated with oral health conditions in individuals with Down syndrome.
• Examining mechanisms of dental, oral, and craniofacial health problems that co-occur in individuals with Down syndrome.
• Developing methods and strategies to prevent, diagnose, and treat oral health conditions that are unique to individuals with Down syndrome.
• Proposing clinical trial readiness studies and clinical trials that develop or adapt existing behavioral, social, and/or organizational strategies to maximize oral health for individuals with Down syndrome, e.g., improve oral hygiene, ensure acceptability of dental care, increase access to oral care, and improve caregiver support and effectiveness.

• Examining Down syndrome and obesity, urologic conditions, type 1 diabetes, autoimmune thyroid disease, and other autoimmune diseases within the purview of NIDDK

• Characterization of how environmental exposures are linked to cognitive/dementia phenotypic variations observed in individuals with Down syndrome.
• Incorporation of animal models to explore how toxicity from environmental agents impact oxidative stress pathways which can exacerbate Down syndrome symptomology.
• Exploration of the genetic susceptibility to environmental exposures influencing progression, onset, and/or severity of the complex clinical outcomes of individuals with Down syndrome.
• Epidemiologic and mechanistic research studies aiming to understand the contribution of environmental exposures on subsequent co-morbidities and/or health factors of individuals with Down syndrome.

• Neurodevelopmental underpinnings of psychopathology, as well as the onset, developmental trajectories, and outcomes of mental health conditions across the lifespan, including depression, anxiety, and psychosis.
• Research from a dimensional perspective is supported to identify fundamental components that span multiple disorders, such as attention, memory, executive function or affective regulation, and may involve developing and/or validating biological markers, developing and/or validating methods or measures to assess domains of psychopathology, and testing integrative models within longitudinal frameworks to track trajectories of risk and protection.
• Discovery of specific genetic variants on chromosome 21 or epigenetic effects of chromosome 21 trisomy that have specific effects on mental health outcomes. Functional validation of the effects of these putative mental health relevant genetic/epigenetic impacts on molecular pathways or cell function is also desired. See or the recent for more details on desired genomics research at NIMH. Validation studies involving animals should refer to the .
• Of interest are supplements relevant to Component 2 of the INCLUDE Research Plan, to add specific Down syndrome cohorts to develop validated measures of psychopathology for these individuals, and to elucidate the onset, course and functional outcomes, including risk and resilience, for individuals with Down syndrome who have comorbid psychopathology. Supplements relevant to components 1 on existing basic science projects will also be considered. NIMH will not support supplements relevant to component 3 of the INCLUDE Research Plan at this time.

• Including individuals with Down syndrome from NIH-designated health disparity populations (Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asians, Native Hawaiians and Other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities) into existing clinical or community-based studies in sufficient number to
• Intersectional stigma and discrimination and their impact on health and healthcare utilization.
• Coping strategies, social support, and other protective factors related to chronic disease risk and outcomes.
• Access to and quality of healthcare, including primary, specialty, and behavioral health care.
• Evaluating the transition from child to adult healthcare and other service systems.

• Addition of a Down syndrome component to a basic research study related to cognitive decline and Alzheimer's disease;
• Understanding the role of aberrant neurotrophin signaling in the cognitive and behavioral characteristics of Down syndrome;
• Development and characterization of animal models of developmental delays, cognitive, dysfunction and cognitive decline in Down syndrome;
• Determine the role of white matter in individuals with Down syndrome.

• NINR is interested in applications related to caregiving and caregivers for individuals with Down syndrome.
• For fellowship (F) awards, NINR will only accept applications to provide support for individuals who have a Bachelor’s degree or higher in nursing to pursue graduate research training that leads to a research doctoral degree. Only nurse applicants are accepted for this program. Applicants are encouraged to submit applications during the first three years of training to ensure that the award will support at least one year of research training. NINR will only accept F31 and F32 applicants.
• For career (K) awards NINR will only accept applications from research doctorate-prepared applicants who have a Bachelor's degree or higher in nursing. NINR will only accept K01 and K23 applicants.

• Engagement of patients and communities in all phases of the translational process
• Integration of special and underserved populations in translational research across the human lifespan
• Innovative processes to increase the quality and efficiency of translational research, particularly of multisite trials
• Use of cutting-edge informatics.
• NCATS is also interested in providing information about the resources available to support clinical research and development of Down syndrome cohorts, including the Recruitment Innovation Centers (RICs), Trial Innovation Centers (TICs), and the Clinical and Translational Science Awards (CTSA) Program. Program staff are also available to provide information on existing NCATS programs such as the Rare Diseases Clinical Research Network (RDCRN) and Therapeutics for Rare and Neglected Diseases (TRND) that may be a source of funding for INCLUDE-related projects.

• Understanding the use of mind and body approaches to improve cognitive function and for managing Down syndrome-associated health conditions (e.g., chronic pain, anxiety disorders, etc.)

• Enhancing existing and creating new animal models for Down syndrome.
• Preference will be given to proposals that develop informative animal models and demonstrate their potential for investigating multiple phenotypic features of Down syndrome, rather than focusing on a specific phenotype of the disease.

Please see Frequently Asked Questions for contact information for participating Institutes and Centers.