Funding Priorities by Institute and Center

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Funding Priorities by Institute and Center

Funding Priorities by Institute and Center

�鶹�� Cancer Institute (NCI)

�鶹�� Eye Institute (NEI)

�鶹�� Heart, Lung, and Blood Institute (NHLBI)

�鶹�� Human Genome Research Institute (NHGRI)

�鶹�� Institute on Aging (NIA)

�鶹�� Institute of Allergy and Infectious Diseases (NIAID)

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

�鶹�� Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS)

�鶹�� Institute on Deafness and Other Communication Disorders (NIDCD)

�鶹�� Institute of Dental and Craniofacial Research (NIDCR)

�鶹�� Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

�鶹�� Institute of Environmental Health Sciences (NIEHS)

�鶹�� Institute of Mental Health (NIMH)

�鶹�� Institute on Minority Health and Health Disparities (NIMHD)

�鶹�� Institute of Neurological Disorders and Stroke (NINDS)

�鶹�� Institute of Nursing Research (NINR)

�鶹�� Center for Advancing Translational Sciences (NCATS)

�鶹�� Center for Complementary and Integrative Health (NCCIH)

Office of Research Infrastructure Programs (ORIP)