Funding

New Funding Opportunities

Notice

Notice of Intent to Publish Notice of Funding Opportunity Announcements for a Federated Biobanking resource for the Down Syndrome Cohort Study Program (DS-CDP) across the lifespan for the INCLUDE Project 

Notice Number

NOT-OD-23-136 

Release Date

June 02, 2023

Application Due Date

November 01, 2023

Earliest Estimated Award Date July 1, 2024
Earliest Estimated Start Date July 1, 2024
Additional Information Frequently Asked Questions
Notice

Notice of Intent to Publish Notice of Funding Opportunity Announcements for a Down Syndrome Clinical Cohort Coordinating Center (DS-4C) for the INCLUDE Project 

Notice Number

NOT-OD-23-135 

Release Date

June 02, 2023

Application Due Date

November 01, 2023

Earliest Estimated Award Date July 1, 2024
Earliest Estimated Start Date July 1, 2024
Additional Information Frequently Asked Questions
Notice

Notice of Intent to Publish Notice of Funding Opportunity Announcements for Down Syndrome Cohort Research Sites (DS-CRS) for the Down Syndrome Cohort Study Program (DS-CDP) across the lifespan for the INCLUDE Project 

Notice Number NOT-OD-23-134
Release Date

June 02, 2023

Application Due Date

November 01, 2023

Earliest Estimated Award Date July 1, 2024
Earliest Estimated Start Date July 1, 2024
Additional Information Frequently Asked Questions
Notice Notice of Special Interest (NOSI): Use of Digital Technology and Mobile Health (mHealth) to Improve Diagnosis, Assessments, Interventions, Management and Outcomes for Individuals with Down Syndrome Across the Lifespan (R21 Clinical Trial Not Allowed)
Notice Number NOT-OD-21-092
Release Date June 28, 2021
Expiration Date November 17, 2023
Notice Clinical Trials Development for Co-Occurring Conditions in Individuals with Down syndrome: Phased Awards for INCLUDE (R61/R33 Clinical Trial Required)
Notice Number RFA-OD-22-010
Release Date April 5, 2022
Application Due Date(s) June 30, 2023; July 1, 2024
Expiration Date July 2, 2024
Notice INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Clinical Trial Readiness (R21 Clinical Trial Not Allowed)
Notice Number RFA-OD-22-007
Release Date April 5, 2022
Application Due Date(s) July 1, 2023; July 1, 2024
Expiration Date July 2, 2024
Notice Transformative Research Award for the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndrome) Project (R01 Clinical Trial Not Allowed)
Notice Number RFA-OD-22-009
Release Date April 5, 2022
Application Due Date(s) July 1, 2023; July 1, 2024
Expiration Date July 2, 2024
Notice Small Research Grants for Analysis, Curation, and/or Sharing of Down syndrome-related Research Data for the INCLUDE Project (R03 Clinical Trial Not Allowed)
Notice Number RFA-OD-22-008
Release Date April 8, 2022
Application Due Date(s) June 30, 2023; July 1, 2024
Expiration Date July 2, 2024
Notice INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Exploratory/Developmental Research Grant Award (R21 Clinical Trial Not Allowed)
Notice Number RFA-OD-21-007
Release Date October 3, 2021
Application Due Date(s)

July 1, 2023; July 1, 2024

Expiration Date July 2, 2024
Notice

NOSI: Ruth L. Kirschstein National Research Service Award (NRSA) Fellowship Awards to Support Training in Research Related to DS as Part of the INCLUDE Project

Notice Number NOT-OD-22-126
Release Date May 18, 2022
Expiration Date April 9, 2024
Notice

NOSI: Mentored Career Development Awards to Foster the Careers of Investigators Pursuing Research Related to Down syndrome as Part of the INCLUDE Project

Notice Number NOT-OD-22-124
Release Date May 24, 2022
Expiration Date November 13, 2024
Notice Notice of Special Interest (NOSI): Community-Based Participatory Research (CBPR) Initiative in Reducing and Eliminating Health Disparities with a focus on addressing diverse representation in research on Down syndrome (R21 Clinical Trial Optional)
Notice Number NOT-OD-22-142
Release Date August 5, 2022
Expiration Date March 17, 2025
Notice

Developing Academic Research Enhancement Award (AREA) and Research Enhancement Award Program (REAP) for Institutions with an emphasis on Down syndrome research (R15 Clinical Trial Not Allowed)

Notice Number NOT-OD-22-136
Release Date May 31, 2022
Expiration Date April 11, 2025
Notice

NOSI: NIH Research Project Grants on Down Syndrome (R01) for the INCLUDE Project

Notice Number NOT-OD-22-123
Release Date May 26, 2022
Expiration Date May 1, 2025
Notice Development of Animal Models and Related Biological Materials for Down Syndrome Research (R24 Clinical Trials Not-Allowed)
Notice Number PAR-22-247
Release Date October 13, 2022
Application Due Date(s)

January 25, 2023; May 25, 2023; September 25, 2023; January 25, 2024; May 25, 2024; September 25, 2024; January 25, 2025; May 25, 2025 (standard due dates)

Expiration Date May 26, 2025
Notice

NOSI: Availability of Administrative Supplements for the INCLUDE Project

Notice Number NOT-OD-22-137
Release Date June 7, 2022
Expiration Date June 2, 2025
Notice Notice of Special Interest (NOSI): Administrative Supplements to NCATS CTSA Program KL2/K12 Institutional Career Development Awards as part of the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndrome) Project
Notice Number NOT-OD-22-192
Release Date October 3, 2022
Application Due Date(s)

July 1, 2023; July 1, 2024; July 1, 2025

Expiration Date July 2, 2025
Notice Notice of Special Interest (NOSI): Administrative Supplements to NCATS CTSA Program T32/TL1 Institutional Training Program as part of the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndrome) Project
Notice Number NOT-OD-22-191
Release Date Spetember 30, 2022
Application Due Date(s)

July 1, 2023; July 1, 2024; July 1, 2025

Expiration Date July 2, 2025
Notice INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Clinical Research Short Course (R25 Independent Clinical Trial Not Allowed)
Notice Number PAR-22-195
Release Date October 3, 2022
Application Due Date(s)

June 27, 2023; June 27, 2024; June 27, 2025

Expiration Date September 8, 2025
Notice Development of Animal Models and Related Biological Materials for Down Syndrome Research (R21 Clinical Trials Not Allowed)
Notice Number PAR-23-067
Release Date October 8, 2022
Application Due Date(s)

March 20, 2023; additional standard NIH due dates apply

Expiration Date January 8, 2026

Funded Projects

2022

Project Title CaMKII nitrosylation in the age-related decline of synaptic plasticity
Awardee University of Colorado, Denver
Project Number 3R01AG067713-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 1R01DC019511-01A1
Funding Opportunity Announcement NOT-OD-20-025
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 3RF1AG064465-01S2
Funding Opportunity Announcement PA-20-272
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 1R13HD108965-01
Funding Opportunity Announcement PA-21-151  
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 1R61HL162839-01
Funding Opportunity Announcement PAR-19-328  
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 1R03HD108261-01
Funding Opportunity Announcement RFA-RM-21-011
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 1R15AG077421-01
Funding Opportunity Announcement PAR-21-155  
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 1R21DC020024-01
Funding Opportunity Announcement PA-20-195  
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 1R21HD105144-01A1
Funding Opportunity Announcement PA-20-195  
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 1R01DC019735-01A1
Funding Opportunity Announcement PA-20-185  
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 1R01DC020229-01
Funding Opportunity Announcement PA-20-185  
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 1R21OD032463-01
Funding Opportunity Announcement PAR-21-167  
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 3R21OD032463-01S1
Funding Opportunity Announcement PAR-21-071  
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 3U19AG068054-02S2
Funding Opportunity Announcement PA-20-272  
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 3U2CHL156291-02S3
Funding Opportunity Announcement PA-20-272
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 3U2CHL156291-02S2
Funding Opportunity Announcement PA-20-272
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 3R21HD105879-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R21HD105879-01S2
Funding Opportunity Announcement NOT-OD-22-057
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 3R21HD106164-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01DK084171-10
Funding Opportunity Announcement PA-19-056
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 1R13CA271716-01
Funding Opportunity Announcement PA-21-151
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 1R01HD105679-01A1
Funding Opportunity Announcement PA-20-185
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 1R01HD107873-01A1
Funding Opportunity Announcement PA-20-185
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 1R01HD109307-01
Funding Opportunity Announcement PA-20-185
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 1F31HD110287-01
Funding Opportunity Announcement PA-21-051
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 2R01HL133230-06
Funding Opportunity Announcement PA-20-185
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 5U19AG068054-03
Funding Opportunity Announcement PAR-19-374
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 1RF1AG079519-01
Funding Opportunity Announcement NOT-OD-20-025
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 1R01AI166835-01A1
Funding Opportunity Announcement NOT-OD-20-025
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 1R01HD105233-01A1
Funding Opportunity Announcement NOT-OD-20-025
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 1K01HD109445-01
Funding Opportunity Announcement NOT-OD-20-021
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 3U19AG068054-03S1
Funding Opportunity Announcement NOT-OD-20-024
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 3RF1AG073979-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 3T32GM007635-44S1
Funding Opportunity Announcement NOT-OD-21-076
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 3T32GM136444-03S1
Funding Opportunity Announcement NOT-OD-21-076
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 3T32GM141742-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01HD101534-01A1S1
Funding Opportunity Announcement NOT-OD-20-024
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 3SC2HD103587-03S1
Funding Opportunity Announcement NOT-OD-22-057
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 3R21HD106125-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R03NS123969-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 1R03AG078730-01
Funding Opportunity Announcement RFA-OD-20-006
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 1R61AG078967-01
Funding Opportunity Announcement RFA-OD-20-003
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 1RF1AG078969-01
Funding Opportunity Announcement RFA-OD-20-005
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 1RF1AG079002-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R01DK135089-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R61HD109748-01
Project Number University of Colorado, Denver
Funding Opportunity Announcement RFA-OD-20-003
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 1R01HD109750-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R01HD109765-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R21HD109777-01
Funding Opportunity Announcement RFA-OD-20-004
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 1R01HD109794-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R61HL165345-01
Funding Opportunity Announcement RFA-OD-20-003
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 1R21HL165364-01
Funding Opportunity Announcement RFA-OD-21-007
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 1R61HL165366-01
Funding Opportunity Announcement RFA-OD-20-003
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 1R21HL165406-01
Funding Opportunity Announcement RFA-OD-21-007
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 1R21HL165411-01
Funding Opportunity Announcement RFA-OD-21-007
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 1RF1NS128739-01
Funding Opportunity Announcement RFA-OD-20-005
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 3U2CHL156291-03S1
Funding Opportunity Announcement NOT-OD-20-024
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 3U19AG068054-03S2
Funding Opportunity Announcement NOT-OD-20-024
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.

   

Project Title Alzheimer Biomarker Consortium - Down Syndrome (ABC-DS)-04 Supplement
Awardee University of Pittsburgh at Pittsburgh
Project Number 3U19AG068054-03S3
Funding Opportunity Announcement NOT-OD-20-024
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 3P30AG072973-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01AG073179-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01DC019092-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01HD098179-03S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01HD101006-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01HD106197-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01HL155104-01A1S1
Funding Opportunity Announcement NOT-OD-20-024
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 RFA-OD-20-006
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 N/A
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 3U24AG057437-04S1
Funding Opportunity Announcement NOT-OD-20-024
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.

2021

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 1R01AI155918-01
Funding Opportunity Announcement

RFA-OD-20-005

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 3R01HL126527-06S1
Funding Opportunity Announcement

NOT-OD-20-129

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 1K23HL155898-01
Funding Opportunity Announcement

NOT-OD-20-021

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 1R01HL156475-01
Funding Opportunity Announcement NOT-OD-20-025
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 5P50HD103525-02
Funding Opportunity Announcement

RFA-HD-20-016

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 5P50HD103526-02
Funding Opportunity Announcement

RFA-HD-20-016

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 1P50HD105328-01
Funding Opportunity Announcement RFA-HD-21-009
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 1P50HD105353-01
Funding Opportunity Announcement

RFA-HD-21-009

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 1P50HD105354-01
Funding Opportunity Announcement

RFA-HD-21-009

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 1R01AG073179-01
Funding Opportunity Announcement NOT-OD-20-025
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 1R01AG073779-01
Funding Opportunity Announcement

RFA-OD-20-005

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 1R01AG073823-01
Funding Opportunity Announcement RFA-OD-20-005
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 3R01AR074875-02S1
Funding Opportunity Announcement NOT-OD-20-129
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 1R01HD102909-01A1
Funding Opportunity Announcement PA-20-185
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 1R01HD106197-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R01HL159494-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R01HL159595-01
Funding Opportunity Announcement

RFA-OD-20-005

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 1R21HD105879-01
Funding Opportunity Announcement

PA-18-482

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 1S10OD030463-01
Funding Opportunity Announcement

PAR-20-114

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 1F31HD105424-01A1
Funding Opportunity Announcement

PA-21-051

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 1R01AG073979-01
Funding Opportunity Announcement

RFA-OD-20-005

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 3R01AI150300-01S2
Funding Opportunity Announcement NOT-OD-20-024
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 3R01HD076189-07S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01HD096085-02S1
Funding Opportunity Announcement NOT-OD-20-023
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 3R01HD098179-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01HD099150-03S1
Funding Opportunity Announcement NOT-OD-20-023
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 1R01HD104640-01A1
Funding Opportunity Announcement NOT-OD-20-025
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 3R01HL130020-06S3
Funding Opportunity Announcement NOT-OD-20-024
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 1R01HL155104-01A1
Funding Opportunity Announcement NOT-OD-20-025
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 3R37NS095733-06S1
Funding Opportunity Announcement NOT-OD-18-194
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 1R03HD106123-01
Funding Opportunity Announcement

RFA-OD-20-006

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 3R03NS108229-01A1S1
Funding Opportunity Announcement NOT-OD-20-024
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 1R03NS123969-01
Funding Opportunity Announcement

RFA-OD-20-006

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 1R21DC019280-01A1
Funding Opportunity Announcement

PA-20-194

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 3R21HD099573-01A1S2
Funding Opportunity Announcement NOT-OD-20-024
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 3R21HD101003-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 1R21HD106125-01
Funding Opportunity Announcement RFA-OD-20-004
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 1R21HD106144-01
Funding Opportunity Announcement

RFA-OD-20-004

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 1R21HD106164-01
Funding Opportunity Announcement

RFA-OD-20-004

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 1R21HL162572-01
Funding Opportunity Announcement

RFA-OD-20-004

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 1R21HD102988-01A1
Funding Opportunity Announcement

PAR-19-376

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 1R61AG074859-01
Funding Opportunity Announcement

RFA-OD-20-003

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 3R61HD100934-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R61AR077495-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R61HL151254-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3T32GM007635-43S1
Funding Opportunity Announcement NOT-OD-20-024
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 3T32GM136444-02S2
Funding Opportunity Announcement NOT-OD-20-024
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 5U19AG068054-02
Funding Opportunity Announcement

PAR-19-374

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 3U19AG068054-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3U24AG057437-04S1
Funding Opportunity Announcement NOT-OD-20-024
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 4R33HL151253-03
Funding Opportunity Announcement RFA-OD-19-018
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 3U24HD090743-06S1
Funding Opportunity Announcement NOT-OD-20-024
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 3U24HL135691-04S1
Funding Opportunity Announcement NOT-OD-20-024
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 3UL1TR002538-04S3
Funding Opportunity Announcement

NOT-OD-20-024

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

NOT-HD-20-039

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 NOT-HD-20-039
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 NOT-HD-20-039
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.

2020

Project Title Polyamines in Down syndrome-Alzheimer’s disease
Awardee University of Denver, Colorado Seminary
Project Number 1R21AG070297-01
Funding Opportunity Announcement RFA-OD-20-004
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 1R01AR078663-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R01AG070153-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R01AG070154-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R01HD103828-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R01HL155691-01
Funding Opportunity Announcement RFA-OD-20-005
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 1R03HL156476-01
Funding Opportunity Announcement RFA-OD-20-006
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 1R03HD103995-01
Funding Opportunity Announcement RFA-OD-20-006
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 1R03HD103908-01
Funding Opportunity Announcement RFA-OD-20-006
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 1U2CHL156291-01
Funding Opportunity Announcement RFA-OD-20-007
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 3KL2TR002490-03S1
Funding Opportunity Announcement NOT-OD-20-022
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 3KL2TR002530-03S1
Funding Opportunity Announcement NOT-OD-20-022
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 3KL2TR002534-03S1
Funding Opportunity Announcement NOT-OD-20-022
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 3KL2TR002539-03S1
Funding Opportunity Announcement NOT-OD-20-022
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 3R21EY031277-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R21HL151256-01S1
Funding Opportunity Announcement NOT-OD-20-024
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 3T32AR007534-34S1
Funding Opportunity Announcement NOT-OD-20-024
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 3T32GM007635-42S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R61AG066543-02S1
Funding Opportunity Announcement NOT-OD-20-024
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 3R01AI150300-01S1
Funding Opportunity Announcement NOT-OD-20-129
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 3R01AI145988-02S1
Funding Opportunity Announcement NOT-OD-20-129
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 3K08HD92610-03S1
Funding Opportunity Announcement NOT-OD-20-129
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 3R01AI150305-01S1
Funding Opportunity Announcement NOT-OD-20-129
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 3R01HL141237-02S1
Funding Opportunity Announcement NOT-OD-20-129
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 3RF1AG056850-01A1S1
Funding Opportunity Announcement NOT-OD-20-129
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 3R01HD090180-05
Funding Opportunity Announcement NOT-OD-20-129
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 1R01HD098179-01A1
Funding Opportunity Announcement PA-19-056
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 2R42HD090772-03A1
Funding Opportunity Announcement PA-19-270
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 1R21HD099573-01A1
Funding Opportunity Announcement PA-18-482
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 1R01HD100607-01A1
Funding Opportunity Announcement PA-19-056
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 2R15HD090603-02
Funding Opportunity Announcement PAR-18-714
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 1R01HD101534-01A1
Funding Opportunity Announcement PA-19-056
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 1U01HL156059-01
Funding Opportunity Announcement RFA-RM-20-006
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 1R01AG070028-01
Funding Opportunity Announcement NOT-OD-20-025
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 1R01DC019279-01
Funding Opportunity Announcement NOT-OD-20-025
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 1R21EY032320-01
Funding Opportunity Announcement RFA-OD-20-004
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 1F31NS118968-01A1
Funding Opportunity Announcement PA-19-195
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 1R21NS119344-01
Funding Opportunity Announcement PA-18-358
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 2R01HD076189-06A1
Funding Opportunity Announcement PA-18-480
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 1R24HD105357-01
Funding Opportunity Announcement NOT-OD-20-017
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 1U19AG068054-01
Funding Opportunity Announcement PAR-19-374
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 1R01CA249867-01
Funding Opportunity Announcement PA-19-056
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.

2019

Project Title Data Coordinating Center for the Pediatric Heart Network
Awardee New England Research Institutes, Inc.
Project Number 3U24HL135691-03S2
Funding Opportunity Announcement RFA-HL-17-005
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 5R01HD088125-02
Funding Opportunity Announcement PA-13-302
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 1R01AI150300-01
Funding Opportunity Announcement RFA-OD-19-016
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 1R01AI150305-01
Funding Opportunity Announcement RFA-OD-19-016
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 5T32AR007534-33
Funding Opportunity Announcement PA-16-152
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 5P30CA046934-31
Funding Opportunity Announcement RFA-OD-19-016
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 3R01DC011038-10S1
Funding Opportunity Announcement PA-19-056
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 1R21EY031277-01
Funding Opportunity Announcement RFA-OD-19-015
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 2T32GM007635-41
Funding Opportunity Announcement PA-18-403
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 1R01HD100935-01
Funding Opportunity Announcement RFA-OD-19-016
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 1R61AR077495-01
Funding Opportunity Announcement RFA-OD-19-018
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 3R01HD093754-02S1
Funding Opportunity Announcement PA-19-056
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 1R01HD101006-01
Funding Opportunity Announcement RFA-OD-19-016
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 1R21HD101003-01
Funding Opportunity Announcement RFA-OD-19-015
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 1R21HD100997-01
Funding Opportunity Announcement RFA-OD-19-015
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 1R61HD100934-01
Funding Opportunity Announcement RFA-OD-19-018
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 5U54HD087011-05
Funding Opportunity Announcement RFA-HD-15-033
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 5U54HD090216-04
Funding Opportunity Announcement RFA-HD-16-013
Summary This project will 1) increase DS-Connect® registry enrollment, 2) extract clinical observations, treatments, and outcomes from PCORnet, the National 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 1R61HL151253-01
Funding Opportunity Announcement RFA-OD-19-018
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 5U24HL135691-03
Funding Opportunity Announcement RFA-HL-17-005
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 1R21HL151261-01
Funding Opportunity Announcement RFA-OD-19-015
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 1R61HL151254-01
Funding Opportunity Announcement RFA-OD-19-018
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 1R61HL138346-02
Funding Opportunity Announcement RFA-RM-16-010
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 3T32HL072738-16S1
Funding Opportunity Announcement NOT-OD-19-087
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 5T32HL007670-30
Funding Opportunity Announcement NOT-OD-19-087
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 1R21NS115593-01
Funding Opportunity Announcement RFA-OD-19-015
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 5UL1TR001857-04
Funding Opportunity Announcement PAR-15-304
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 Pitt+Me.
Project Title ITM 2.0: Advancing Translational Science in Metropolitan Chicago
Awardee University of Chicago
Project Number 5UL1TR002389-03
Funding Opportunity Announcement PAR-15-304
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 1R61AG066543-01
Funding Opportunity Announcement RFA-OD-19-018
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 1R21CA245067-01
Funding Opportunity Announcement PA-19-111
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 5T32GM008730-20
Funding Opportunity Announcement PA-19-111
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 3R01HD090180-04S1
Funding Opportunity Announcement PA-19-056
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 3U54HD079123-05S1
Funding Opportunity Announcement RFA-HD-14-012
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 1R21HD101000-01
Funding Opportunity Announcement RFA-OD-19-015
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 5U54HD090256-04
Funding Opportunity Announcement RFA-OD-19-015
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 3R01HL134940-03S1
Funding Opportunity Announcement PA-19-056
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 1R01HL151260-01
Funding Opportunity Announcement RFA-OD-19-016
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 1R01HL151260-01
Funding Opportunity Announcement RFA-OD-19-016
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 1R21HL151256-01
Funding Opportunity Announcement RFA-OD-19-015
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 1R01HL151257-01
Funding Opportunity Announcement RFA-OD-19-016
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 5UL1TR001873-04
Funding Opportunity Announcement PAR-15-304
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 5UL1TR002535-02
Funding Opportunity Announcement RFA-OD-19-016
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.

2018

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.

Past Funding Opportunities

Notice INCLUDE (Investigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Predoctoral to Postdoctoral Fellow Transition Award (F99/K00 Clinical Trial Not Allowed)
Notice Number RFA-OD-23-016
Release Date May 8, 2023
Application Due Date(s) July 1, 2023
Expiration Date July 2, 2023
Notice Notice of Special Interest (NOSI): Discovery of the Genetic Basis of Conditions Associated with Down Syndrome for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project (X01)
Notice Number NOT-OD-23-042
Release Date February 8, 2023
Application Due Date(s) March 21, 2023
Expiration Date March 22, 2023
Notice
Notice of Change to NOT-OD-20-025: 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
March 19, 2021
Application Due Date(s)
June 5, 2021, October 5, 2021
Expiration Date
January 7, 2022
Notice
Notice of Change to NOT-OD-20-024: Availability of Administrative Supplements for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project
Notice Number
Release Date
March 19, 2021
Application Due Date(s)
May 12, 2021, July 23, 2021, November 23, 2021, March 23, 2022, July 23, 2022
Expiration Date
July 24, 2022
Notice
Notice of Special Interest (NOSI): Competitive Supplements/Revisions (R01) Available for INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndromE) Project (Competitive Supplement/Revision Clinical Trial Optional)
Notice Number
Release Date
December 18, 2019
Application Due Date(s)
March 5, 2021; July 5, 2021; November 5, 2021; March 5, 2022; July 5, 2022
Expiration Date
September 8, 2022
 
Notice
Notice of Special Interest (NOSI): Development of Animal Models of Down Syndrome and Related Biological Materials as Part of 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)
  • For R24 applications submitted via RFA-OD-19-027: May 26, 2021, September 28, 2021 and January 26, 2022, May 26, 2022
  • For R21 applications submitted via PAR-19-369: February 16, 2021; June 16, 2021; October 16, 2021; February 16, 2022; June 16, 2022
Expiration Date
September 9, 2022
Notice
Notice of Special Interest (NOSI): Administrative Supplements to NCATS CTSA Program KL2 Institutional Career Development Awards as part of the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndrome) Project
Notice Number
Release Date
September 25, 2020
Application Due Date(s)
November 1, 2021, November 1, 2022
Expiration Date
November 2, 2022
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 National 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
Notice
Notice of Special Interest (NOSI) regarding the Availability of Urgent Competitive Revisions and Administrative Supplements for Research on Coronavirus Disease 2019 (COVID-19) in Individuals with Down Syndrome for the INCLUDE Project
Notice Number
Release Date
June 25, 2020
Application Due Date(s)
March 12, 2021, July 12, 2021
Expiration Date
July 13, 2021
Notice
Clinical Trials Development for Co-Occurring Conditions in Individuals with Down syndrome: Phased Awards for INCLUDE (R61/R33 Clinical Trial Required)
Notice Number
Release Date
December 13, 2019
Application Due Date(s)
November 3, 2021
Expiration Date
November 4, 2021
Notice
INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Clinical Trial Readiness (R21 Clinical Trial Not Allowed)
Notice Number
Release Date
December 13, 2019
Application Due Date(s)
November 3, 2021
Expiration Date
November 4, 2021
Notice
Transformative Research Award for the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndrome) Project (R01 Clinical Trial Not Allowed)
Notice Number
Release Date
December 13, 2019
Application Due Date(s)
November 3, 2021
Expiration Date
November 4, 2021
Notice
Small Research Grants for Analyses of Down Syndrome-related Research Data for the INCLUDE Project (R03 Clinical Trial Not Allowed)
Notice Number
Release Date
December 13, 2019
Application Due Date(s)
November 3, 2021
Expiration Date
November 4, 2021
Notice
Notice of Special Interest (NOSI): Discovery of the Genetic Basis of Conditions Associated with Down Syndrome for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project (X01)
Notice Number
Release Date
December 16, 2020
Expiration Date
February 20, 2021
Notice
Notice of Special Interest (NOSI): Discovery of the Genetic Basis of Conditions Associated with Down Syndrome for the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project (X01)
Notice Number
Release Date
January 28, 2022
Expiration Date
March 01, 2022
Notice
Notice of Special Interest (NOSI): Administrative Supplements to NCATS CTSA Program KL2 Institutional Career Development Awards as part of the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndrome) Project
Notice Number
Release Date
December 19, 2019
Expiration Date
March 3, 2020
Notice
Development of the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndromE) Project Data Coordinating Center (U2C)
Notice Number
Post Date
December 13, 2019
Expiration Date
February 15, 2020
More Information
  • The application consists of four components: Overall, Administrative and Outreach Core, Data Portal Core and Data Management Cores. Each component is allowed a Research Strategy section up to 12 pages and each will have a budget section.
  • FAQ from INCLUDE Data Coordinating Center Pre-Application Webinar that INCLUDE Program staff hosted for prospective applicants.
Notice
Notice of Clarification of Application Submission Information for NOT-OD-19-071 "Notice of Availability of Competitive Supplements/Revisions for the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndromE) Project
Notice Number
Post Date
February 27, 2019
Expiration Date
March 20, 2019
Notice
INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Clinical Trial Readiness (R21 Clinical Trial Not Allowed)
Notice Number
Post Date
February 5, 2019
Expiration Date
March 15, 2019
Notice
Transformative Research Award for the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndrome) Project (R01 – Clinical Trial Not Allowed)
Notice Number
Post Date
February 5, 2019
Expiration Date
March 15, 2019
Notice
Clinical Trials Development for Co-Occurring Conditions in Individuals with Down syndrome: Phased Awards for INCLUDE (R61/R33 Clinical Trials Required)
Notice Number
Post Date
February 5, 2019
Expiration Date
March 15, 2019
Notice
Notice of Availability of Competitive Supplements/Revisions for the INCLUDE (Investigation of Co-occurring Conditions across the Lifespan to Understand Down syndromE) Project (Competitive Supplement/Revision Clinical Trial Optional)
Notice Number
Post Date
February 5, 2019
Expiration Date
See listed due dates in Notice.

Funding Priorities by Institute and Center

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

National Cancer Institute (NCI)

  • 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.

National Eye Institute (NEI)

  • 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.

National Heart, Lung, and Blood Institute (NHLBI)

  • 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.

National Human Genome Research Institute (NHGRI)

  • 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.

National Institute on Aging (NIA)

  • 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.

National Institute of Allergy and Infectious Diseases (NIAID)

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

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  • 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® (https://DSConnect.nih.gov) 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.

National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS)

  • 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.

National Institute on Deafness and Other Communication Disorders (NIDCD)

  • 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.

National Institute of Dental and Craniofacial Research (NIDCR)

  • 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.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

National Institute of Environmental Health Sciences (NIEHS)

  • 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.

National Institute of Mental Health (NIMH)

  • 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 the NIMH Genomics Council Work Group Report or the recent nature article for more details on desired genomics research at NIMH. Validation studies involving animals should refer to the Notice of NIMH’s Considerations Regarding the Use of Animal Neurobehavioral Approaches in Basic and Pre-clinical Studies.
  • 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.

National Institute on Minority Health and Health Disparities (NIMHD)

  • 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.

National Institute of Neurological Disorders and Stroke (NINDS)

  • 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.

National Institute of Nursing Research (NINR)

  • 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.

National Center for Advancing Translational Sciences (NCATS)

  • 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.

National Center for Complementary and Integrative Health (NCCIH)

  • 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.)

Office of Research Infrastructure Programs (ORIP)

  • 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.

This page last reviewed on September 22, 2023