Frequently Asked Questions

Which NIH Institutes and Centers (IC) are participating in the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndrome) project?

National Cancer Institute (NCI)
National Eye Institute (NEI)
National Heart, Lung, and Blood Institute (NHLBI)
National Human Genome Research Institute (NHGRI)
National Institute on Aging (NIA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of General Medical Sciences (NIGMS)
National Institute of Mental Health (NIMH) 
National Institute on Minority Health and Health Disparities (NIMHD) 
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Nursing Research (NINR)
National Center for Advancing Translational Sciences (NCATS)
National Center for Complementary and Integrative Health (NCCIH) 

What are the funding priorities of each Institute and Center?

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.

Whom should I contact if I have a specific question about an IC’s scientific priorities?

Anna E. Mazzucco, Ph.D.
Office of the Director, National Institutes of Health (NIH)
Telephone: 301-451-1220
Email: anna.mazzucco@nih.gov 

Christina H. Park, Ph.D.
Environmental Influences on Child Health Outcomes (ECHO)
Office of the Director, National Institutes of Health (NIH)
Telephone: 301-435-4013
Email: parkchris@mail.nih.gov

Sige Zou, Ph.D.
Office of Research Infrastructure Programs (ORIP)
Office of the Director, National Institutes of Health (NIH)
Telephone: 301-435-0749
Email: zous@mail.nih.gov

Malcolm A. Smith, M.D., Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6087
Email: Malcolm.Smith@nih.gov

Malgorzata Klauzinska, Ph.D.
​National Cancer Institute (NCI)
Telephone: 240-276-5181
Email: klauzing@nih.gov

Houmam Araj, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: arajh@nei.nih.gov

Huiqing Li, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0554
Email: huiqing.li@nih.gov

Charlene Schramm, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-3793
Email: SchrammC@nhlbi.nih.gov

Jyoti G. Dayal, M.S.
National Human Genome Research Institute (NHGRI)
Telephone: 301-480-2307
Email: jyotig@nih.gov

Laurie M. Ryan, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: ryanl@mail.nih.gov

Frosso Voulgaropoulou, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID
Telephone: 240-627-3205
Email: fvoulgaropoulou@niaid.nih.gov

Marie Mancini, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: mancinim2@mail.nih.gov

Melissa A. Parisi, M.D., Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6880
Email: parisima@mail.nih.gov

Sujata Bardhan, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-0471
Email: sujata.bardhan@nih.gov 

Kelly King, Ph.D.
National Institute on Deafness and Other Communication Disorders (NIDCD)
Telephone: 301-402-3458
Email: kingke@nidcd.nih.gov

Jason Wan, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-9898
Email: JasonWan@nidcr.nih.gov

Jonathan Hollander, Ph.D. 
National Institute of Environmental Health Sciences (NIEHS)
Telephone:  984-287-3269
Email:  jonathan.hollander@nih.gov

Michael Humble, Ph.D.  
National Institute of Environmental Health Sciences (NIEHS)
Telephone:  984-287-3272
Email:  humble@niehs.nih.gov

Donna Krasnewich-Vostal
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-443-6954
Email: dkras@nigms.nih.gov

Tara Dutka, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-451-3074
Email tara.dutka@nih.gov

Lisa Gilotty, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3825
Email: gilottyl@mail.nih.gov

Nathan Stinson, Jr., M.D., Ph.D.
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8704
Email: stinsonn@mail.nih.gov

Robert Riddle, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5745
Email: rr260c@nih.gov

David Banks, Ph.D., MPH, RN        
National Institute of Nursing Research (NINR
Telephone: 301-496-9558
Email: banksdh@mail.nih.gov

Rebekah S. Rasooly, Ph.D.
National Institute of Nursing Research (NINR
Telephone: 301-827-2599
Email: rr185i@nih.gov

Erica Rosemond, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-8927
Email: rosemonde@mail.nih.gov 

Peter Murray, Ph.D.
National Center for Complementary and Integrative Health (NCCIH)
Telephone: 301-396-4054
Email: peter.murray@nih.gov

How many awards has NIH funded under the INCLUDE Project?

Since its implementation in fiscal year 2018, the INCLUDE Project has supported over 130 research awards. Please see the Funding page for details about past Funding Opportunity Announcements and Funded Projects.

How many awards does NIH intend to fund under the INCLUDE Project for fiscal year 2021 (FY21)?

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Currently, funding mechanisms have not been finalized for FY21. However, Funding Opportunity Announcements will be posted on the Funding page as they become available.

Is a resource sharing plan required for my INCLUDE project?

Yes. All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan. The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program.It is expected that the results of INCLUDE-funded research will be shared with the wider scientific community in a timely manner. NIH intends to maximize the availability of publications and the sharing of underlying data and biospecimens for INCLUDE-supported supplements and projects.

Under the goals of INCLUDE, recipients are required to develop a Public Access and Data Sharing and Management Plan that (1) describes their proposed process for making resulting publications and biospecimens, and to the extent possible, the underlying primary data immediately and broadly available to the public; (2) if applicable, provides a justification to NIH if such sharing is not possible. Underlying primary data should be made as widely and freely available as possible while safeguarding the privacy of participants and protecting confidential and proprietary data. Additional instructions are provided in the Resource Sharing Plan section of each RFA. Investigators are encouraged to submit their human subjects data to the INCLUDE Data Coordinating Center (DCC).

Where can I find assistance in recruiting a cohort of individuals with Down syndrome and/or planning a clinical trial for a co-occurring condition in Down syndrome?

Investigators responding to components 2 or 3 may need some assistance in developing a cohort of subjects with Down syndrome to achieve their study goals, or in clinical trial design and planning. Several resources exist to help with clinical and translational research. The National Center for Advancing Translational Sciences (NCATS) supports the Recruitment Innovation Center (RIC), the Trial Innovation Centers (TICs), and the Clinical Translational Science Awards to facilitate clinical research, clinical trials, and subject recruitment and engagement. Investigators can also propose to use DS-Connect®: The Down Syndrome Registry to help with recruitment for their projects; to do so, register a professional account with DS-Connect and/or contact the registry coordinator at DSConnect@nih.gov. In addition, applications addressing components 2 or 3 should strongly encourage participants with Down syndrome or their caregivers to register in DS-Connect.

Who do I contact if I have questions?

If you have questions that are not included in the FAQ, please email: anna.mazzucco@nih.gov.

This page last reviewed on March 9, 2021