Building Health through Multidomain Resilience Research from Molecules to Communities: Mechanisms, Measures, and Biomarkers

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Topic Description

Post Date: August 28, 2026

Expiration Date: August 25, 2028

Purpose: This topic aims to accelerate rigorous, reproducible, interdisciplinary resilience science to promote health and well-being across the lifespan and populations. Resilience mechanisms operate across scales and domains to maintain health, enabling prevention and recovery from chronic and acute diseases despite known risk factors. The focus is research on protective pathways and their biological mechanisms that maintain physiological functions throughout the life course; harmonized terminology; standardized protocols; validated measures, biomarkers and implementation science to optimize evidence-based interventions (including lifestyle) across populations, including children, tribal communities, and groups at-risk for health disparities.

Background: Resilience spans whole-person systems integrating molecular, cellular, physiological, and psychological levels within social communities and environmental contexts. Translating the multiscale, multidomain nature of resilience has been limited by heterogeneous definitions, models, and measures. NIH defines resilience broadly as a living system’s capacity to resist, recover, adapt, or grow from challenges or stressors, with outcomes tracked over time across interconnected individual, community, and environmental systems (Brown et al, 2023). High-priority research includes developing/refining resilience measures and metrics; data interoperability; advancing mechanistic understanding of protective and restoring factors distinct from disease-risk reduction; and identifying biomarkers that reflect or predict resilience. Aligned applications would define the challenge/stressor, system(s) and resilience response/outcome(s); include at least one domain of analysis, preferably cross domains to accelerate translation into implementable prevention, treatment, and recovery strategies.

Participating ICOs

National Heart, Lung, and Blood Institute (NHLBI)

NHLBI is interested in studies that:

  •  Use data science and precision health to define individual heart, lung, blood, and sleep health signatures, including resilience metrics, stressors, tipping points, trajectories, and longitudinal outcomes (resistance, recovery, adaptation, growth)
  • Leverage large biomedical resources: NHLBI-funded cohort studies,Trans-omics for precision medicine (TOPMed), Researching COVID to enhance recovery (RECOVER), All of Us, LungMap, etc.
  • Identify mechanisms that preserve, enhance or restore homeostasis under stress and explain sustained health despite known risk, e.g. hypertension without stroke; full recovery post-heart valve surgery; preserved lung function despite tobacco exposure, or interplay of resilience and sickle cell disease exacerbation e.g., vaso-occlusive crises
  • Integrate multidomain exposures and biopsychosocial factors (e.g. mindfulness, belief systems, optimism), community engagement,  and include all populations within mission
ICO Scientific Contact:
NHLBI Highlighted Topics
[email protected]

National Center for Complementary and Integrative Health (NCCIH)

NCCIH is interested in research that advances understanding of resilience as a whole-person, multilevel process and informs strategies for health promotion, disease prevention, recovery, and overall well-being across the lifespan. Areas of interest include:

  • Identifying, validating, and promoting modifiable protective pathways and factors that contribute to resilience across molecular, cellular, physiological, behavioral, psychological, social, and environmental domains. 
  • How complementary and integrative health approaches, lifestyle, and environmental factors affect biological and behavioral mechanisms that enhance the capacity to resist, recover, adapt, or grow in response to stressors and health challenges. 
  • Mechanistic research to identify and validate measures and biomarkers of resilience and to generate evidence supporting the implementation of effective resilience-promoting strategies across a range of populations and settings.
IC may give special consideration to support meritorious applications in this topic area.
ICO Scientific Contact:
Erin Burke Quinlan, PhD
[email protected]

Jennifer Baumgartner
[email protected]

National Cancer Institute (NCI)

NCI seeks projects that advance mechanistic understanding and interventions across cancer biology, prevention, and control, particularly studies that:

  • Develop, refine, or validate multilevel measures, biomarkers, and resilience signatures to defined stressors across cancer risk, tumor initiation, progression, treatment, and survivorship.
  • Identify protective factors and mechanisms enabling resistance to malignant transformation or favorable outcomes despite genetic, environmental, behavioral, or biological risk, including, but not limited to, DNA repair, immune surveillance, microbiome-host interactions, epigenetic stability, inflammation resolution, and metabolic adaptability.
  • Use advanced analytics in large, diverse longitudinal cohorts and mechanistic studies in patients, human tissues, and/or model systems to design, test, or implement interventions and strategies for risk stratification, early detection, prevention behaviors, treatment tolerance, and survivorship.
ICO Scientific Contact:
NCI Resilience HT Team
[email protected]

National Institute on Aging (NIA)

NIA interests include the following as it relates to resilience in older individuals:

  • Development and validation of dynamic resilience measures using controlled perturbations and longitudinal monitoring
  • Advanced analytics for multisystem resilience phenotyping 
  • Impact of age, early-life, psychosocial, and other factors on changes in neurobiological, molecular, cellular, physiological, social, and behavioral resilience mechanisms; how these factors, individually and interactively, influence the severity of and recovery from stressors; and how dysregulation or modulation of these mechanisms, particularly in those with multiple contributors to impaired resilience, shape aging-related clinical endpoints
  • Shared and tissue-specific pathways and mechanisms of inter-organ or system-level coordination 
  • Mechanisms underlying sex differences
  • Therapeutic targets for and mechanisms by which interventions improve resilience and preserve/restore clinical outcomes in representative populations 
ICO Scientific Contact:
Stacy Carrington-Lawrence, Ph.D.
[email protected]

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIAAA seeks research on mechanisms shaping alcohol use, alcohol-related outcomes, recovery, and resilience across biological, behavioral, psychological, social and environmental levels. Priority goes to reproducible studies that identify protective pathways and biomarkers, explain heterogeneity, and inform prevention and intervention.

  • Longitudinal lifespan cohort studies using multimodal AI to integrate biological, behavioral, and environmental data and identify resilience to AUD and alcohol harms, including resistance recovery, adaptation, and influences such as inter-brain synchrony, social enrichment, peer context, sleep, community and environmental factors.
  • Reverse translational and New Approach Methodologies studies of cellular, molecular and circuit mechanisms that promote resilience despite alcohol risk exposure. 
  • Integrative multiomic studies of heterogeneity in resilience to AUD, emphasizing protective pathways, validated biomarkers and standardized, reproducible measures.
ICO Scientific Contact:
Laura Kwako
[email protected]

Miri Gitik
[email protected]

National Institute on Minority Health and Health Disparities (NIMHD)

NIMHD supports solutions-oriented biological, behavioral, clinical, and population science research focused on resilience among populations with health disparities, such as:

  • Identifying novel biological, behavioral, social, and environmental mechanisms that shape resilience across the life course, and elucidating pathways that buffer or mitigate stress-related health effects.
  • Developing measures, biomarkers, and scalable interventions that generalize across populations and community contexts
  • Applying community-engaged, systems science, data science, and translational approaches to advance resilience research and it’s real-world impact
  • Examining epigenetic processes, vagal nerve function, and environmental-biological interactions to identify mechanisms and clinical targets for resilience
  • Investigating relationships between psychological resilience, and the onset, severity, and progression of health events, as well as recovery duration, quality, and long-term outcomes
IC may dedicate funds available to support applications in this Topic area depending upon the availability of funds, the number of meritorious applications, and competing ICO priorities.
IC may give special consideration to support meritorious applications in this topic area.
ICO Scientific Contact:
Rada Dagher, Ph.D., M.P.H
[email protected]

Office of Behavioral and Social Sciences Research (OBSSR)
This office does not award grants. Applications must be relevant to the objectives of at least one of the participating Institutes or Centers listed in this topic.
ICO Scientific Contact:
Janine Simmons, M.D.
[email protected]

Office of Disease Prevention (ODP)

For this topic, ODP is particularly interested in projects that test interventions to promote health and well-being in individuals, families, communities, or populations facing biological, social, economic, or environmental challenges. ODP encourages research that enhances protective factors across the life course to prevent disease and disability, improve well-being, and reduce the long-term burden of disease.

This office does not award grants. Applications must be relevant to the objectives of at least one of the participating Institutes or Centers listed in this topic.
ICO Scientific Contact:
Valerie Robinson, PhD, M.Phil, MHA.
[email protected]

Office of Dietary Supplements (ODS)

The ODS seeks to advance research on how dietary supplements (DS) i.e., oral interventions of vitamins, minerals, natural products, botanicals, fatty acids, proteins, amino acids, or other bioactive food constituents affect physiological, metabolic, cognitive, and immune resilience across the lifespan. Studies using repeated measures and challenge-recovery designs to test whether DS help resist, recover, adapt, or grow after aging-related, infectious, metabolic, psychosocial, or environmental stressors are emphasized. Specific research interests include, but are not limited to:

  • Elucidating biological mechanisms or protective pathways through which DS influence adaptive responses to physiological stressors. 
  • Identifying/validating DS exposure biomarkers associated with maintenance or recovery of physiological function, resistance to defined stressors, or adaptive capacity.
  • Developing/validating ways to measure resilience in a dietary supplementation context.
This office does not award grants. Applications must be relevant to the objectives of at least one of the participating Institutes or Centers listed in this topic.
ICO Scientific Contact:
Adam J. Kuszak, Ph.D.
[email protected]

Office of Research on Women's Health (ORWH)

The Office of Research on Women’s Health (ORWH) is interested in projects that:

  • Advance resilience research across the life course relevant to women’s health, including pregnancy, menopause, and aging
    • Incorporate sex as a biological variable in resilience mechanisms, measures, biomarkers, and trajectories
    • Address sex differences in multidomain resilience, including through computational models, to support rigorous, generalizable prevention, treatment, and recovery strategies

The Office of Autoimmune Disease Research in ORWH (OADR-ORWH) is interested in:

  • Research focused on the role of stressors on early immune changes in the prodromal phase of autoimmunity
    • Resilience as an immunopreventative strategy for autoimmune disease
    • Utilizing federated data platforms to enhance pattern recognition in complex multiomic datasets, enabling deeper insights into the multimodal drivers of autoimmune disease pathogenesis and co‑occurring autoimmune diseases
This office does not award grants. Applications must be relevant to the objectives of at least one of the participating Institutes or Centers listed in this topic.
ICO Scientific Contact:
Marquitta White, M.S., Ph.D.
[email protected]

Victoria Shanmugam, MBBS, FRCP, FACR, CCD
[email protected]

Tribal Health Research Office (THRO)
This office does not award grants. Applications must be relevant to the objectives of at least one of the participating Institutes or Centers listed in this topic.
ICO Scientific Contact:
Sheila Caldwell, PhD
[email protected]

Christopher Barnhart, PhD
[email protected]

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