National Institute on Aging > NIA-specific Challenge Grants
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American Recovery and Reinvestment Act of 2009

NIH Challenge Grants in Health and Science Research (RFA-OD-09-003)

National Institute on Aging

NIH has received new funds for Fiscal Years 2009 and 2010 as part of the American Recovery & Reinvestment Act of 2009 (Recovery Act), Pub. L. No. 111-5. The NIH has designated at least $200 million in FYs 2009 – 2010 for a new initiative called the NIH Challenge Grants in Health and Science Research.

This new program will support research on topic areas that address specific scientific and health research challenges in biomedical and behavioral research that would benefit from significant 2-year jumpstart funds.

The NIH has identified a range of Challenge Areas that focus on specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds to quickly advance the area in significant ways. Each NIH Institute, Center, and Office has selected specific Challenge Topics within the broad Challenge Areas related to its mission. The research in these Challenge Areas should have a high impact in biomedical or behavioral science and/or public health.

NIH anticipates funding 200 or more grants, each of up to $1 million in total costs, pending the number and quality of applications and availability of funds. In addition, Recovery Act funds allocated to NIH specifically for comparative effectiveness research (CER) may be available to support additional grants. Projects receiving these funds will need to meet this definition of CER: “a rigorous evaluation of the impact of different options that are available for treating a given medical condition for a particular set of patients. Such a study may compare similar treatments, such as competing drugs, or it may analyze very different approaches, such as surgery and drug therapy.” Such research may include the development and use of clinical registries, clinical data networks, and other forms of electronic health data that can be used to generate or obtain outcomes data as they apply to CER.

The application due date is April 27, 2009.


Broad Challenge Areas and Specific Challenge Topics

Note: Those marked with an asterisk (*) are the highest priority topics; however, applicants may apply to any of the topics.

The National Institute on Aging (NIA) is interested particularly in aging-relevant and age-related aspects of the topics listed below.

(01) Behavior, Behavioral Change, and Prevention

01-AG-101 Advanced analyses for social network health data. Many aspects of health and disease are now understood to take place in a rich social context, and the analyses of the network structure of real (and virtual) communities promises many insights into the processes by which health-related beliefs, norms, and behavior patterns are transmitted. Although the mathematics of networks and the complex systems they imply have become increasingly more tractable, significant challenges remain in the design and implementation of analyses that are robust to data limitations or model mis-specification. Contact: Dr. John Haaga, 301-496-3131,

01-AG-102 Neural mechanisms of behavioral change. Studies aimed at elucidating the neural mechanisms underlying behavioral changes during aging or age-related diseases and disorders, including choice of food and nutrition or the amount of physical activities. Contact: Dr. Molly Wagster, 301-496-9350,

01-AG-103 Individual-based model of social behavior. Development of a robust and well-characterized individual-based model of social behavior that includes the dynamics of social interactions and that matches observed patterns of behavior. Contact: Dr. Lis Nielsen, 301-402-4156,

01-AG-104 Test default options to promote healthier behaviors. Exploration by behavioral economists and clinicians to develop and test default options (e.g., placement of fresh fruit displays in stores, the location of parking spaces at the workplace) to promote healthier behaviors. Contact: Dr. John Phillips, 301-496-3138,

01-AG-105 Measurement of culturally-shared mental phenomena. Development of new tools for the measurement of: culturally-shared mental phenomena (e.g., representations, scripts, prejudices); mechanisms by which these phenomena are transferred and adapted across individuals, and the distribution and transmission of cultural phenomena within populations. Contact: Dr. Jonathan King, 301-402-4156,

01-AG-106 Identifying phenotypic markers for positive behavior change. Identify reliable, robust intermediate phenotypic markers (using cognitive neuroscience and behavioral economics) that can be used to personalize approaches to support positive health behavior change in the near term. Examples include behavioral disinhibition, delay discounting, heart rate variability and implicit cognition. Contact: Dr. Jonathan King, 301-402-4156,

01-AG-107 Functional roles of neuroimmune factors in mediating behavior. Emerging data suggest that physiological functions of neuroimmune factors, such as cytokines and chemokines, are not restricted to mediating neuroinflammatory responses but may be considered as a new class of neurotransmitter, neuromodulator, or neurohormone in the brain. This paradigm shift offers a new framework to understand the roles of neuroimmune factors in a variety of behavioral conditions such as excessive drinking, anxiety, depression, etc. Contact: Dr. Molly Wagster, 301-496-9350,

01-AG-108 Capturing social network information for groups at high risk for negative health behaviors. Emerging evidence indicates that social networks influence health behaviors such as eating habits, alcohol consumption, and smoking. Research in this area is needed to enhance existing methodologies and/or devise novel methods that will capture social network information among groups at heightened risk for particular negative health behaviors. Contact: Dr. Jonathan King, 301-402-4156,

01-AG-109 Development of behavioral and social interventions that reduce stigma and improve quality and accessibility of health care services in low resource settings. In the same manner that the effects of stigma magnify the personal and societal problems related to diseases and disorders (e.g., mental health conditions, addiction, HIV), preventing or mitigating stigma and its effects can profoundly improve the lives of individuals, their families and the larger society. There is a critical need to translate existing knowledge related to the causes and consequences of stigma into scalable pilot interventions that can measure stigma and prevent or mitigate its negative effects on health. Contact: Dr. Sid Stahl, 301-402-4156,

(02) Bioethics

02-RR-101* Recontact Issues in Genotype and Genome-Wide Association Studies. Genotype and genome-wide association studies create challenging re-contact issues if subjects are later to be asked to return for clinical research including phenotyping. Applicants would propose 2-year awards for pilot programs that would be implemented at 3 or more affiliated sites to develop and apply IRB guidelines that addressed ethical barriers (e.g., re-contacting) in genotype – phenotype studies. This idea is submitted through NCRR on account of the ethics work underway at the Clinical and Translational Science Awards (CTSAs) and, if accepted, would be developed with NHGRI’s ELSI Division. NCRR Contact: Andrea Sawczuk, 301-435-0792,; NIA Contact: Dr. Robin Barr, 301-402-7715,

02-HG-101* Informed consent and data access policies. The creation of large databases that include genomic information on individual participants, coupled with the move to universal electronic medical records, makes it increasingly possible to identify individual research participants in databases, despite efforts to “de-identify” their data, and potentially to unearth an individual’s private medical information. Research is urgently needed to address the implications of this for recruitment, informed consent, and data access policies in biomedical research. Contact: Dr. Jean McEwen, 301 402-7997,; NIA Contact: Dr. Robin Barr, 301-402-7715,

02-OD(OSP)-101* Unique Ethical Issues Posed by Emerging Technologies. Advances in biotechnology and biomedical science raise novel ethical, legal, and social issues. Research in this area is needed to understand the unique ethical concerns related to emerging technologies (e.g. biotechnology, tissue engineering, nanomedicine, and synthetic biology). These include issues such as dual use research, privacy, safety, intellectual property, commercialization and conflict of interest, among others. Research is also needed to assess how these novel issues are addressed under current oversight and regulatory structures and identify where there may be gaps and/or need for revised or new oversight approaches. OD(OSP) Contact: Abigail Rives, 301-594-1976,; NIA Contact: Dr. Robin Barr, 301-402-7715,

02-OD(OSP)-102* Ethical Issues in Health Disparities and Access to Participation in Research. Research is needed to assess the under-representation in biomedical and clinical research of U.S. minority populations, underserved populations, and populations who may be vulnerable to coercion or undue influence, to identify barriers to participation in research and to develop approaches for overcoming them. Additionally, studies are needed to assess the impact and ethical considerations of conducting biomedical and clinical research internationally in resource-limited countries. OD(OSP) Contact: Abigail Rives, 301-594-1976,; NIA Contact: Dr. Robin Barr, 301-402-7715,

02-OD(OSP)-103* Ethical Issues Associated with Electronic Sharing of Health Information. The development of an electronic health information infrastructure and the sharing of health information for patient care and research offers enormous promise to improve health care and promote scientific advances. However, the broad sharing of such data raises numerous ethical issues that may benefit from additional studies (e.g. those related to privacy and confidentiality). Examples include studies to assess risks associated with health information technology and the broad sharing of health information for research, and novel approaches for mitigating them. Examination could also include analysis of current oversight paradigms and suggestions for enhancements, as well as assessments of how privacy risks may change in the future. OD(OSP) Contact: Abigail Rives, 301-594-1976,; NIA Contact: Dr. Robin Barr, 301-402-7715,

02-OD(OSP)-104* Ethical Issues in the Translation of Genetic Knowledge to Clinical Practice. Genetics and genomics have great promise for the development of personalized medicine, yet the ethical, legal and social implications of both the research and application of genetic and genomic knowledge and technology are far reaching. Studies are needed to better understand the factors that influence the translation of genetic information to improved human health and the associated ethical issues. Examples of studies include those to address ethical issues related to broad sharing and use of new genetic information and technologies for research to improve human health, human subjects protection in genetic and genomic research, the identifiability of genetic/genomic information and how our understanding of identifiability is evolving, return of research results and incidental findings to subjects, alternative models of informed consent for broad data sharing for research, and the impact of intellectual property (IP) issues on development of new technologies. OD(OSP) Contact: Abigail Rives, 301-594-1976,; NIA Contact: Dr. Robin Barr, 301-402-7715,

02-OD(OSP)-105* Ethical Issues Raised by the Blurring between Treatment and Research. The distinction between clinical practice and research is growing less clear, a trend that may be more pronounced with respect to genetic information and medical records research. Studies are needed to better understand the ethical issues associated with this trend. Examples of studies include those to identify how this blurring in roles affects traditional human subjects protections, including, for example, essential practices such as informed consent, conceptions of the doctor/patient and investigator/subject relationship, and privacy protections. OD(OSP) Contact: Abigail Rives, 301-594-1976,; NIA Contact: Dr. Robin Barr, 301-402-7715,

(03) Biomarker Discovery and Validation

03-AG-101 Novel assays for dried blood spots. Population surveys including biomarkers have invigorated the social sciences, but requirements for very large sample sizes frequently make the collection of blood unfeasibly expensive, while storage costs and conditions are quite high. Recent advances in biochemistry, however, have made it possible in principle to derive rich profiles of important lipids, proteins, metabolites, and genetic information from dried blood spots that could be more systematically exploited through the development and perfection of new assays and their eventual implementation in larger biobanking facilities. Contact: Dr. John Haaga, 301-496-3131,

03-AG-102 Novel biomarkers for Alzheimer’s Disease. Development and testing of novel tissue or fluid (e. g. blood, cerebrospinal fluid) biomarkers of Alzheimer's disease for mechanism based therapeutic target validation, early disease diagnosis, disease progression, or response to therapeutic interventions. Contact: Dr. Neil Buckholtz, 301-496-9350,

03-AG-103 Biomarkers for neurodegenerative diseases. Identification of sensory and/or motor biomarkers for age-related neurodegenerative diseases in relevant animal models or human subjects. Contact: Dr. Neil Buckholtz, 301-496-9350,

03-AG-104 Biomarkers, stress, and immune function. Identification of biomarkers to assess the impact of stress, both social and biological, on immune function. Contact: Dr. Ronald Kohanski, 301-496-6402,

03-AG-105 Biomarkers, oxidative stress, and dietary supplements. Development and validation of biomarkers of oxidative stress that could be used to assess the antioxidant effects of dietary supplements in vivo and to examine their mechanisms of action, efficacy, and effectiveness with respect to human health. Contact: Dr. David Finkelstein, 301-496-7847,

03-AG-106 Biomarkers for pain. Pain research has been greatly hampered by the unreliable nature of self-report based instruments. The establishment of objective, affordable, and reliable pain biomarkers would advance our understanding of pain mechanisms, provide a basis for improved clinical management of pain, help assess an individual's risk for becoming addicted to opiate analgesics, and establish much needed objective measures of treatment success or failure. Contact: Dr. Wen Chen, 301-496-9350,

03-AG-107 Role of immunity in neurodegenerative diseases of the eye. Oxidative stress/injury and host immune response are postulated to be involved in many degenerative eye diseases such as age-related macular degeneration, diabetic retinopathy, uveitis, glaucoma, and keratoconus. Characterizing the molecular events and how the host responds to these insults will allow us to identify biomarkers for the diagnosis and treatment of these blinding diseases. Contact: Dr. Wen Chen, 301-496-9350,

03-AG-108 Developing high-throughput biomarker assays from finger-stick dried blood spots. Develop, using finger-stick dried blood spots, novel high-throughput biomarker assays, to identify lipids, proteins, metabolites, and genetic information to expand the array of available biomarkers for use in large community-based biosocial surveys. Contact: Dr. John Haaga, 301-496-3131,

03-AG-109 Biomarkers of persistent damage after acute joint injury. Define early biochemical and structural changes that arise after joint injury, such as trauma or anterior cruciate ligament (ACL) tears, which would serve as indicators that could be analyzed in subsequent longitudinal studies to seek biomarkers for progression to early osteoarthritis (OA). These could be used for both preventive intervention, and as preliminary indications for pathways of disease pathogenesis to guide therapeutic development. Contact: Dr. Chhanda Dutta, 301-435-3048,

03-AG-110 Develop novel imaging, proteomic, or genomic approaches to identify risk for fragility fractures. Projects may use existing data sets to define and validate measures of bone quality that are more predictive than bone mineral density measurements. Contact: Dr. Sherry Sherman, 301-435-3048,

03-AG-111 Validation of biomarkers that bridge animal models with proof of concept (Early Phase IIa) studies for mental/nervous system disorders. Identify and validate useful biomarkers that associate with a beneficial response to treatment in animal models and can be measured in patients. These can then be utilized as targets in early Phase IIa Proof of Concept studies to determine whether a therapeutic intervention has engaged the intended biologic target. Contact: Dr. Neil Buckholtz, 301-496-9350,

03-AG-112 Identify and validate clinically relevant, quantifiable biomarkers of diagnostic and therapeutic responses for blood, vascular, cardiac, and respiratory tract dysfunction. Patients who appear to be similar because of their clinical characteristics often demonstrate substantially different morbidity, mortality, and responses to drugs. Identification and validation of biomarkers from cell culture to animal models and human studies could be used to determine the most effective care for individual patients and more precisely identify those who are most likely to benefit from specific interventions for prevention or treatment. Contact: Ms. Winifred Rossi, 301-496-3836,

(04) Clinical Research

04-AG-101* Therapeutic algorithms for older patients with multiple conditions: data analyses and pilot testing. Analysis of existing medical record data sets (e.g., from the VA or HMOs) to identify problems associated with the combination of therapies for two or more specific conditions in older patients with multiple conditions. This information could be used to develop new therapeutic algorithms or refine existing algorithms to address problems related to the use of multiple algorithms in older clinically complex patients and to inform short-term intervention studies to assess their efficacy and practicality. Contact: Dr. Susan Nayfield, 301-496-6949,

04-AG-102 Pain and Neurodegenerative Diseases. Research to understand the impact of aging or age-related neurodegenerative diseases on the neural pathways underlying pain experience as well as the underlying mechanisms and the influence of aging or age-related neurodegenerative diseases on the assessment and treatment of pain in the elderly. Contact: Dr. Wen Chen, 301-496-9350,

04-AG-103 Development of treatments for the metabolic syndrome. The metabolic syndrome, which is a combination of medical disorders manifested as central obesity, dyslipidemias, fatty liver disease, hyperinsulinemia and insulin resistance, affects at least one in five (maybe even one in four) people in the USA and prevalence increases with age. It leads to shortening of life and increasing morbidity because of diabetes and cardiovascular disease. Rather than treating each component of the metabolic syndrome separately, it would be beneficial and less expensive in the long run, if a unifying pathophysiology for metabolic syndrome were uncovered. This could then potentially lead to developing of treatments for its prevent and treatment. Contact: Dr. Susan Nayfield, 301-496-6949,

04-AG-104 Development of Less Expensive and More Effective Treatments for Medical Conditions, e.g., Restless Legs Syndrome. It is estimated that approximately 16 million Americans have symptoms of Restless Legs Syndrome with 1/3 reporting significantly diminished quality of life because of those symptoms. Current FDA-approved treatments are limited, costly, do not have sustained, long-term benfits, and in fact may lead to worsening of the condition with very long-term treatment. Alterantive and less costly treatments are now ready and waiting to be developed that would both save money for the health care system and potentially improve treatment of the RLS patient, possibly even correcting an underlying pathology of the diseease, but as these offer no potential commercial gain they require federal support for development and clinical evaluation. Contact: Dr. Brad Wise, 301-496-9350,

04-AG-105 Development of experience-based measures of well-being. Almost all measures of the quality of life and life satisfaction are based on self-evaluations and judgments rather than on cumulating actual experience over the course of a day, week, etc. Studies of how people remember and report these experiences show that systematic distortions can prevent reporting of accurate experiences after the fact. Brief, standardized measures of experienced, subjective well-being, based on experience sampling approaches, would offer a unique tool for clinical and epidemiological research, augmenting and complementing current indicators of population wellbeing and quality of life. Such measures are not included in PROMIS or the NIH Toolbox. Measuring both the evaluative and experiences facets of well-being is likely important for understanding health, which is not just the absence of illness, but the presence of wellness. Contact: Dr. Lis Nielsen, 301-402-4156,

04-AG-106 Development of better methods to measure “real world” caloric intake and physical activity in people. Precise quantitative knowledge of individuals’ caloric intake and level of physical activity in their daily lives is crucial to assessing the success of interventions designed to modify them, as well to assess their health effects. To date, both objective and self-reported measures of these variables have remained very imperfect. Research to improve reliability and practicality of stable-isotope metabolic methods and body composition measures used in objective estimation of caloric intake, and of accelerometers or other objective measures of physical activity, as well as improved self-report instruments, could play an important role in developing better interventions to control weight and assess their effects. Contact: Dr. Sergei Romashkan, 301-435-3047,

04-AG-107 Mechanisms of specific benefits of different types of physical activity. Different types of physical activity (e.g., resistance exercise, endurance exercise, walking) have different physiologic effects and differing effects on specific health outcomes and risk factors. Greater knowledge of the physiologic and cellular effects (e.g., on muscle, body composition, blood vessels, metabolism, and bone) of specific types of physical activity could lead to better physical activity interventions targeted for specific conditions, risk factors, or disabilities. This information could be obtained through short-term physical activity or exercise intervention studies that combine measures of clinical or functional outcomes with physiological or cellular information from biospecimens. Contact: Dr. Sergei Romashkan, 301-435-3047,

04-AG-108 Drug response and toxicity. Application of pharmacogenetics and pharmacogenomics, quantitative and systems pharmacology (this could be part of a larger grouping to include systems biology and systems genetics), ADMET pharmacology, pre-clinical models, new technologies and approaches to complement pharmacogenomic studies to enhance signal to noise ratios and aid mechanistic studies, and consensus standards for normal and altered phenotypes in drug response and toxicity. Contact: Ms. Winifred Rossi, 301-496-3836,

04-AG-109 Develop and validate behavioral metrics to measure the impact of chronic pain. It will also be important to identify and measure the factors influencing human pain perception and transitions to chronic pain after an acute insult. Contact: Dr. Wen Chen, 301-496-9350,

04-AG-110 Methods to enhance palliative care and end-of-life research. Develop and test interventions to enhance the quality of care for persons with a life-threatening illness. This research will provide the foundation for the development of evidenced-based guidelines to standardize palliative and end-of-life care. Contact: Dr. Lis Nielsen, 301-402-4156,

04-AG-111 Development of effective approaches to increase minority recruitment and retention into clinical trials. Focus on research activities that reduce barriers to diversity and participation in clinical trials and on initiatives that build partnerships and utilize new and non-traditional recruitment approaches. Specific health disparity diseases/conditions of concern include but are not limited to diabetes, obesity, cardiovascular disease, infant mortality, cancer, substance abuse, mental health, and HIV/AIDS. Contact: Dr. Taylor Harden, 301-496-9265,

(05) Comparative Effectiveness Research

05-AG-101* Data Infrastructure for Post-Marketing Comparative Effectiveness Studies. The challenge is to create the data infrastructure that will enable comparisons of particular therapies, prescribing patterns, and benefit designs on health outcomes. Problems with currently available studies include omission of key patient groups (such as the elderly in nursing homes), lack of information on adherence and outcomes in polypharmacy, lack of information on outcomes across different insurance benefit designs, and lack of information on actual prescribing patterns and outcomes across regions and over time. Responsive projects could include: (1) Data linkages to allow studies of diffusion of therapies and comparisons of their effects on outcomes, health care utilization and expenditures across hospital referral regions, hospitals, and physician practices; (2) Linkage of Medicaid administrative data and Medicare Part D claims data for comparative research on prescribing patterns and patient outcomes in the nursing-home population; (3) Linkage of prescription drug data to data banks such as those maintained by the Alzheimer’s Disease Neuroimaging Initiative to allow comparative research on outcomes in defined patient populations; (4) Supplements to longitudinal data sets and ongoing clinical trials to allow comparisons of the effects of alternative benefit designs on adherence, patient outcomes and health care expenditures; (5) Analyses of how context (geographic region, hospitals, insurance) affects comparative effectiveness studies of two or more interventions; (6) Data linking features of health and prescription drug insurance (public or private) to utilization of health services and health outcomes; and (7) Planning grants for comparative effectiveness research using and building the data infrastructure on these topics. NIA Contacts: Dr. John Haaga, 301-496-3131,; and Dr. John Phillips, 301-496-3138,

05-AG-102* Prevention and Risk Factor Reduction Strategies for Disabilities. A variety of risk factors contribute to disabilities in activities of daily living and instrumental activities of daily living in older persons. Reduction in the number of individuals’ risk factors has been shown to reduce risks of certain causes of disabilities, such as falls. However, effective risk-factor reduction strategies require a high degree of coordination of care across diverse health services and settings. Alternative strategies to achieve this coordination in risk-reduction interventions could be tested in two-year studies. In addition, planning grants could develop protocols for clinical trials to compare the effectiveness of different pharmacologic (e.g. analgesic) and lifestyle (e.g. physical activity) interventions to prevent a variety of disability outcomes, such as loss of walking ability and cognitive disability, for which current data do not provide a clear basis for comparison. Secondary analyses of existing clinical trial data and expanded data collection on ongoing trials could also address these issues. NIA Contacts: Dr. Sergei Romashkan, 301-435-3047, and Ms. Georgeanne Patmios, 301-496-3138,

05-AG-103* Imaging and Fluid Biomarkers for Early Diagnosis and Progression of Aging-related Diseases and Conditions including Neurodegenerative Diseases. Diseases and conditions of aging have a huge public health burden, and the ability to diagnose these early and follow their course would greatly help in treating and managing them. Various imaging modalities and fluid biomarkers have been proposed as being useful for early diagnosis and following the course of diseases and conditions of aging including neurodegenerative diseases such as Alzheimer’s disease. However, most studies have not compared multiple imaging and/or fluid biomarkers in the same study with the same study participants to evaluate their comparative effectiveness at being able to provide for the early diagnosis or for following the progression of disease. Two-year grants could be used to analyze data from available studies which include multiple imaging and fluid biomarker measures (e.g. MRI and PET imaging; blood, urine, or cerebrospinal measures of disease-associated molecules) or to plan or implement new studies which would incorporate multiple imaging and/or fluid biomarker modalities for early diagnosis and/or progression of conditions and diseases of aging including neurodegenerative diseases. NIA Contact: Dr. Neil Buckholtz, 301-496-9350,

05-104* Planning Grants and Pilot Studies for Comparisons of Management Strategies for Older Patients with Multiple Coexisting Conditions. The majority older individuals suffer from multiple coexisting conditions. This poses challenges for medical management in regard to factors such as adverse interactions of drugs used for different conditions, and conflicting recommendations from treatment guidelines for different individual conditions. Different treatment strategies to optimize health and quality-of-life outcomes need to be compared to identify strategies that provide the best risk-benefit ratios for such older patients. Two-year planning grants, and pilot feasibility testing for different management strategies could contribute to this goal. Although many clinical trials testing pharmacological, behavioral, or community-level interventions to remediate or prevent aging-related disorders or declines in function have established the efficacy of specific interventions, we know much less, however, about the comparative effectiveness of these approaches. Two-year planning grants to develop protocols for clinical trials directly testing the comparative effectiveness of these different intervention types would be appropriate, as would comparative effectiveness analyses of data from existing clinical trials data. Specific examples of target domains that could benefit from either further analysis or planning activities include the following: (1) The comparison of different types of interventions (e.g., different anti-inflammatories and behavioral interventions) for the prevention of Alzheimer’s disease; (2) The comparison of efficacious treatments (e.g., physical exercise vs. cognitive training) for the remediation of age-related cognitive decline exclusive of dementia. NIA Contact: Dr. Sergei Romashkan, 301-435-3047,

05-AG-105* Comparative Intervention Trials for Diseases and Syndromes of Aging Including Neurodegenerative Diseases. Although many clinical trials testing pharmacological, behavioral, or community-level interventions to remediate or prevent aging-related disorders or declines in function have established the efficacy of specific interventions, we know much less, however, about the comparative effectiveness of these approaches. Two-year planning grants to develop protocols for clinical trials directly testing the comparative effectiveness of these different intervention types would be appropriate, as would comparative effectiveness analyses of data from existing clinical trials data. Specific examples of target domains that could benefit from either further analysis or planning activities include the following: (1) The comparison of different types of interventions (e.g., different anti-inflammatories and behavioral interventions) for the prevention of Alzheimer’s disease; (2) The comparison of efficacious treatments (e.g., physical exercise vs. cognitive training) for the remediation of age-related cognitive decline exclusive of dementia; and (3) Comparisons of interventions for “geriatric syndromes”, such as urinary incontinence and involuntary weight loss. NIA Contacts: Dr. Laurie Ryan, 301-496-9350,; Dr. Jon King, 301-402-4156,; Dr. Molly Wagster, 301-496-9350,; and Dr. Sergei Romashkan, 301-435-3047,

(06) Enabling Technologies

06-AG-101* Neuroscience Blueprint: Development of non-invasive imaging approaches or technologies that directly assess neural activity. This could include research on imaging neuronal electrical currents, neurotransmitter changes and/or neuronal/glial cell responses to brain circuit activation. This scientific area could be advanced by improvements/refinements in existing imaging technology or use of emerging technology that could be developed in two years. The outcome of this challenge could have high impact by connecting the system-level, large population view afforded by fMRI with the cellular processes and responses that contribute to the BOLD-fMRI signal. Two-year challenge projects could stimulate the development of human brain imaging techniques that link cell activity underlying neural communication to the structure and function of brain circuits, and could complement other brain connectivity imaging modalities. Contact: Dr. Bradley Wise, 301-496-9350,

06-AG-102 Nanoreporters for health during aging. With a few exceptions such as heart failure and prostate cancer, diagnostic biomarkers have been difficult to dissect from the thousands of physiological metabolites present in the circulation or secretions. State-of-the-art technologies using nanosensors have been developed in order to measure and report on specific disease states or conditions in real time. Biochemical compounds for specific metabolic pathways can be embedded in nanomaterials that can be recovered selectively, and the changes in these compounds can be determined by mass spectrometry or other analytical technologies. Nanosensors (nanoreporters) can be used in lieu of endogenous metabolites to assess metabolic function during aging and the metabolic syndrome. The selection of suitable compounds could be developed in model organisms as a function of aging or development of metabolic syndrome. In addition to their value as discovery tools, the outcomes could be “translated” rapidly for human use, contingent upon safety considerations. Contact: Dr. Bradley Wise, 301-496-9350,

06-AG-103 Understanding the neural mechanisms responsible for tinnitus. Millions of Americans suffer from chronic tinnitus, or the percept of ringing in one or both ears. The numerous mechanisms that underlie tinnitus are very poorly understood, and as a consequence, the known intervention strategies are ineffective for most affected individuals. The challenge is to understand the specific neural mechanisms giving rise to tinnitus and to develop novel intervention strategies. Contact: Dr. Wen Chen, 301-496-9350,

06-AG-104 Development of new tools and technologies to interrogate human mitochondrial function in vivo. These tools would include methods to manipulate human mitochondrial structure and activity, as well as novel imaging techniques to monitor and measure human mitochondrial function or dysfunction in healthy and diseased tissues. Contact: Dr. David Finkelstein, 301-496-7847,

06-AG-105 Tools facilitating chemistry and biology collaborations. Development of chemical probes, imaging agents, radiochemicals, and other tools for understanding biology through collaborations between a chemist(s) and a biologist(s). Contact: Dr. Jose Velazquez, 301-496-6428,

06-AG-106 New computational and statistical methods for the analysis of large data sets from genome-wide association studies (GWAS) and the use of next-generation sequencing technologies. Develop new tools to enable the translation of vast amounts of genomic information into medical benefit to address large amounts of data generated (e.g., terabases of sequence) that overwhelm existing computational resources and analytic methods. These new approaches include very large-scale genotyping and sequencing studies, metagenomics, transcriptomics, and genetic network analysis. Contact: Dr. Marilyn Miller, 301-496-9350,

06-AG-107 Measuring the body burden of emerging contaminants: Biosensors and lab “on-chip” technology for measuring in vivo environmental agents. New advances in biosensors and lab-on-chip technology create novel ways to measure the body burden and sub-clinical health effects of emerging contaminants in the environment in large study populations. Additional research funds would support field testing of the most promising sensors and analysis techniques through collaboration with existing epidemiologic studies taking advantage of both new and banked tissue specimens. Contact: Ms. Winnie Rossi, 301-496-3836,

06-AG-108 Technologies for obtaining genomic, proteomic, and metabolomic data from individual viable cells in complex tissues. Develop technologies that are able to use one or a small number of cells are needed to generate data to understand the molecular phenotype, or state, of a particular cell type and the role it plays in tissue and organ function in health and disease. Contact: Dr. Jose Velazquez, 301-496-6428,

06-AG-109 Brain imaging and higher order states. Exploration of brain imaging technologies to provide insight into higher-order states such as awareness of self, focused attention, stress, meditative states, calm and other emotional states; utilize brain imaging to develop objective measures and rigorous, quantitative evaluation of subjective states. Contact: Dr. Molly Wagster, 301-496-9350,

(07) Enhancing Clinical Trials

07-AG-101 Validating NIH Neuroscience Blueprint Toolbox assessments. Validation of NIH Toolbox assessments in multiple clinical populations (AD, ADHD, PD etc.) by leveraging currently funded NIH clinical studies. Contact: Dr. Molly Wagster, 301-496-9350,

07-AG-102 Biological samples in the NIH Neuroscience Blueprint Toolbox. Collection, genotyping and archiving of biological samples in n=5800 national random sample (ages 3 - 85 years) used in the NIH Toolbox assessment norming, including a 12 month longitudinal reassessment of the national sample. Contact: Dr. Molly Wagster, 301-496-9350,

07-AG-103 Development of methodologies and scientific tools for improving and/or assessing the external validity of randomized clinical trial (RCT) results to known populations. The practice of conducting RCTs with volunteer samples recruited from patients in clinical or community settings limits the generalizability of results, a critical problem for comparative effectiveness research. Research is needed to develop scientific tools for improving and/or assessing the external validity of RCT results to known populations, including methods for applying probability sampling in the identification and recruitment of RCT participants, measuring biases in RCT participant pools, and accounting for such biases in the analysis of RCT results. Contact: Dr. Sergei Romashkan, 301-435-3047,

07-AG-104 New and innovative technologies to monitor patient behaviors and clinical status in clinical trials. Develop and test new affordable, technologies to enable remote, centralized monitoring of physiologic, behavioral and neurologic indices as well as study medication compliance, and adverse effects in clinical trials. These technologies should provide opportunities to enhance efficiency in clinical trials, as well as to collect more “real life” data. Contact: Dr. Sergei Romashkan, 301-435-3047,

(08) Genomics

08-AG-101* Genetic factors affecting rates of change in disease risk factors with age. Human aging is associated with an increase in the levels of numerous chronic disease risk factors, but the rates at which these factors increase with age varies considerably among persons. There is evidence that genetic factors influence rates of age-related change, but there have been few studies to identify specific factors. The identification of genetic factors which protect against such adverse aging changes could contribute significantly to the development of interventions for healthier aging. The recent acquisition of genome-wide SNP data from several large long-term longitudinal studies provides the opportunity to identify genes affecting rates of change of important risk factors efficiently by analyzing phenotype data collected on individuals over decades, combined with information from the SNP scans. Such genes could also be identified by other approaches, such as linkage analyses and studies of rare variants in candidate genes. Proposals for analyses to identify relationships of specific genetic factors to rates of change with age in phenotypes measured in longitudinal studies of young, middle-aged, or older populations are encouraged. Contact: Ms. Winifred Rossi, 301-496-3836,

08-AG-102 Epigenetic changes. Identification of epigenetic changes that are specifically associated with age-related neurodegenerative diseases. Contact: Dr. Suzana Petanceska, 301-496-9350,

08-AG-103 Environmental factors. Identification of environmental factors that are associated with age-related neurodegenerative diseases and disorders and the influence of these environmental factors on the properties and function of the relevant nervous system. Contact: Dr. Suzana Petanceska, 301-496-9350,

08-AG-104 Genetic and epigenetic predictors of symptom severity. Support research on the genetic underpinnings of symptom severity, and identify individuals at greatest risk for symptoms from both acute and chronic conditions. Design individualized interventions that will maximize symptom management. Contact: Dr. Susan Nayfield, 301.496.6949,

08-AG-105 Approaches to study the interactions among individual behaviors, social and physical environments, and genetic/epigenetic processes during critical developmental periods. Research is needed to develop analytic methods, systems science approaches, or computational models designed to address the interactions among individual behaviors, social and physical environments and genetic/epigenetic processes during critical developmental periods and over time. Contact: Dr. John Haaga, 301-496-3131,

08-AG-106 Cross-disease research to identify commonly targeted pathways or mechanisms between low incidence, neurogenetic disorders with high incidence, population-based disease. Progress in treating many common neurological and neurobehavioral disorders has been hindered by the complex genetics and heterogeneous etiologies of these disorders. However, analyzing related or clinically overlapping Mendelian disorders or studying rare genetic variants of large effect can yield unique biological insight into the mechanisms underlying common disease. Focus on studies that dissect pathways common to simple and complex genetic disorders, with the goal of identifying potential therapeutic targets. Contact: Dr. Steven Snyder, 301-496-9350,

08-AG-107 Approaches to study the interactions among individual behaviors, social and physical environments, and genetic/epigenetic processes during critical developmental periods. Research is needed to develop analytic methods, systems science approaches, or computational models designed to address the interactions among individual behaviors, social and physical environments and genetic/epigenetic processes during critical developmental periods and over time. Contact: Dr. John Haaga, 301-496-3131,

08-AG-108 Technology and resources for high-throughput functional analysis of functional elements in genomic sequences. Develop robust, high-throughput methods to carry out functional assays to determine whether and how putative functional elements (e.g., genes and regulatory sequences) operate to determine cell states in development, health, and disease. Such new methods should include both cellular and whole organism methods to allow systematic analysis of the effects of both genetic (normal variation and mutation) and environmental perturbations, and should include methods for both molecular (transcriptomic, proteomic) analysis and high-throughput phenotyping. Dr. Anna McCormick, 301-496-6402,

08-AG-109 Identifying causal genetic variants associated with heart, lung, and blood diseases. Utilize application of targeted DNA capture and massively parallel sequencing technologies followed by selective genotyping of DNA samples from large well-phenotyped populations. Two applications of this approach are needed: (a) targeted resequencing of entire chromosomal regions already known from GWAS findings to be strongly associated with disease, and (b) disease or other clinical trait-based exome-wide resequencing for the unbiased discovery of rare variants having large effects. Contact: Ms. Winifred Rossi, 301-496-3836,

(09) Health Disparities

09-AG-101* Geographic Disparities in Medicare Usage and Cost. It is well documented that there are major geographic differences across the U.S. in quality of care and clinical outcomes for older adult populations. Moreover, these differences are not correlated with the extent and cost of Medicare usage. Research is needed to (1) foster evidence-based approaches to financing, staffing, public health programs, and clinical practice to reduce these disparities and (2) develop interventions to reduce disparities in one or multiple categories of health determinants − e.g., geography, socioeconomic status, race/ethnicity − using techniques that can be duplicated in a variety of community settings. Contact: Dr. Sidney Stahl, 301-402.4156,

09-AG-102 Creating transformational approaches to address rural health disparities. Research will focus on approaches, partnerships, and technologies for improving rural health outcomes. Additional focus on innovative outreach strategies that involve collaboration among traditional and non-traditional groups including new categories of community health workers, non-traditional occupations and settings. Contact: Dr. Sidney Stahl, 301-402.4156,

09-AG-103 Trans-disciplinary research to integrate the biological and non-biological determinants of health to address health disparities. Research interests include trans-disciplinary approaches to address health disparities through collaborative efforts and sustained partnerships with social scientists, policy researchers, health researchers, environmental scientists, and behavioral scientists, among others. Strategies that develop community infrastructure and networks, including non-traditional partnerships are also of interest. Contact: Dr. Sidney Stahl, 301-402.4156,

(10) Information Technology for Processing Health Care Data for Research

10-AG-101 Adapt existing genetic and clinical databases to make them interoperable for pharmacogenomics studies. In order for personalized approaches to drug therapy to be developed, genetic data and clinical data need to be superimposed. Analysis of the superimposed data will generate hypotheses concerning genetic control of drug efficacy. Contact: Dr. Susan Nayfield, 301.496.6949,

10-AG-102 Information technology demonstration projects facilitating secondary use of healthcare data for facilitating secondary use of healthcare data for research. Determine potential benefit of the analysis of enormous amounts of aggregate, anonymous, healthcare data for obtaining evidence for best practices and identifying promising areas for additional research. Develop policies and technology to ensure stringent protection of individual privacy for aggregate anonymous data used for research. Examples of responsive topics include, but are not limited to: multi-institutional data repository research querying projects; vocabulary and ontology standards in data repositories; policies, process, and governance of data repositories; Extract, Transform, Load (ETL) procedures for data for uses for data for clinical data research repositories. Contact: Dr. John Phillips, 301-496-3138,

(11) Regenerative Medicine

11-AG-101 Musculoskeletal and skin tissue regeneration. Define the molecular pathways that regulate the integration of muscle, tendon, and bone into functional units. Develop applicable animal models for regeneration of musculoskeletal or skin tissues. Define outcome measures, such as non-invasive analysis of disease, injury, and repair. Contact Dr. John Williams, 301-496-6402,

11-AG-102 Hair cell regeneration and maintenance in the ear. Develop and validate methods to regenerate and maintain hair cells in animal model systems with the eventual goal of successful translation to human treatments. Contact Dr. Wen Chen, 301.496.9350,

(12) Science, Technology, Engineering and Mathematics (STEM) Education

12-AG-101 Efficacy of educational approaches toward promoting STEM competencies. Research on efficacy testing of educational pedagogy, tools, and curricula (both classroom and non-classroom approaches) that are targeted at improving student understanding of science, technology, engineering, and math (STEM) concepts. Contact: Dr. Chyren Hunter, 301-496-9322,

(13) Smart Biomaterials - Theranostics

13-AG-101 Theranostics: Combined delivery of diagnostic and therapeutic agents. Development of novel approaches to deliver combined diagnostic and therapeutic agents to appropriate sites with high specificity and in adequate concentrations to realize the promise of combined diagnosis and treatment of diseases in a single sitting (“theranostics”). Contact: Dr. Susan Nayfield, 301-496-6949,

13-AG-102 Novel self-healing smart dental and bio-restorative materials. Dental materials and other biomaterials have limited survival when placed in the human body. Develop a new generation of “self-healing” and “smart” dental and bio-restorative materials that can diagnose structural failure and repair themselves to minimize the loss of natural structures associated with materials failure. Contact: Ms. Winnie Rossi, 301-496-3836,

13-AG-103 Methods to evaluate the health and safety of nanomaterials. Develop novel tools and approaches to determine the impact on biological systems and health outcomes of an array of engineered nanomaterials. Conduct biological, physical and chemical characterization of selected nanomaterials to aid in setting standards for health and safety, and developing computational models for the prediction of long term secondary effects. Contact: Dr. Ron Kohanski, 301-496-6402,

(14) Stem Cells

14-AG-101* Induced Pluripotent Stem (iPS) Cells for Aging and Neurodegeneration Research. Studies have shown that human skin cells can be reprogrammed to become pluripotent stem cells and that such iPS cells act like embryonic stem cells in that they can develop into different cell types. Generating tissue-specific differentiated cells from iPS cells could allow studies on the molecular and cellular changes that characterize aging and neurodegenerative processes. Studies on iPS cells could determine whether they can be used as cell-based models of aging and disease, such as Alzheimer’s disease. Two year challenge projects could stimulate the development of, and biological studies on, iPS cells derived from human tissue of different ages and disease states, and could lead to novel drug screening approaches and open up the possibility of individualized cell therapy. Understanding the differentiation of skin-derived iPS cells. Contact: Dr. Brad Wise, 301-496-9350, or Dr. Ronald Kohanski, 301-496-6402,

14-AG-102 Development of stem cell treatment for degenerative diseases of the eye. Identify biomarkers that can define stem cells and the end-stage cells, as well as reproducible protocols for the generation and purification of viable terminally differentiated cells. The restorative properties of stem cells hold the promise in the treatment of degenerative eye diseases such as macular degeneration, diabetic retinopathy, retinitis pigmentosa and glaucoma, and diseases of the ocular surfaces. Contact: Dr. Wen Chen, 301.496.9350,

14-AG-103 Induced pluripotent stem cells: Cellular and humanized mouse models of disease. Somatic cells, such as fibroblasts, from patients with diseases can be used to create cell lines, tissues and, perhaps, organ systems, through induced Pluripotent Stem Cell (iPSC) technology. Such models could be used to elucidate underlying pathology of disease or screen for agents that could be used therapeutically. Combining this approach with mouse strains able to accept multiple human tissues without rejection could provide the microenvironmental milieu to support the tissue’s physiological function within the context of the whole organism, enabling greater understanding of disease pathogenesis and providing a platform for preclinical testing of drug candidates. Contact: Dr. Ronald Kohanski, 301-496-6402,

14-AG-104 Delineate factors that control the differentiation of pluripotent stem cells in the skin and musculoskeletal system into different lineages. Define the cells’ phenotypes as they differentiate along these pathways. Develop a common vocabulary for stem cell differentiation states. Contact: Dr. Ronald Kohanski, 301-496-6402,

14-AG-105 Exploratory studies of induced pluripotent stem (iPS) cells from healthy individuals and patients with mental/nervous system disorders. This is an effort to reverse-engineer human disease study by generating and characterizing iPSCs from human control and patient populations. Research topics can include maximizing derivation efficiency, maintenance, or reproducibility, studies of cellular differentiation, screening bioactive agents, or profiling the molecular signature as well as the functional properties of cells from controls vs patients. There will be an emphasis on appropriate validation of iPS cells and their derivatives, evaluating the hetero/homogeneity of any cell populations to be screened and use of cellular assays relevant to normal development, organ function and disease. Contact: Dr. Ronald Kohanski, 301-496-6402,

14-AG-106 Developing molecular signatures for heart, vascular, lung, and blood diseases by profiling reprogrammed induced pluripotent stem cells derived from affected individuals of defined genotype. Large-scale profiling of RNA, proteins, and metabolites derived from normal and disease tissues has been instrumental in identifying the molecular etiologies of numerous disorders, but the applicability of this approach has been limited by the availability of relevant biological materials. Cell-based models of disease generated from stem cell technologies could be readily profiled with available high-throughput methods. Contact: Dr. Ronald Kohanski, 301-496-6402,

(15) Translational Science

15-AG-101 Nose-Brain Barrier. Research to manipulate or to design novel vehicles for overcoming the nose-brain-barrier to deliver CNS therapies for age-related neurodegenerative diseases. Contact: Dr. Steven Snyder, 301-496-9350,

15-AG-102 New models and measures in pre-clinical chronic pain research. Existing animal models of temporomandibular or orofacial pain conditions inadequately reflect the pathology or the phenotypes of the human state. Development of new animal models to study the transition from acute to chronic pain in temporomandibular joint disorders or other orofacial pain disorders, coupled with the development of new functional and behavioral assays of acute and chronic pain would be a powerful means to enhance our understanding of the biological mechanisms underlying the development of these chronic pain conditions and the responses of patients to therapeutic interventions. Contact: Dr. Wen Chen, 301-496-9350,

15-AG-103 Protein misfolding in degenerative diseases of the eye. A number of ocular genetic diseases occur due to misfolding/aggregation of proteins, for example the visual pigment protein, rhodopsin in retinitis pigmentosa, crystallins in age-related cataracts, and myocillin in glaucoma. Identifying therapeutic pharmacological agents/drugs that prevent the misfolding/aggregation of proteins could provide new tools for treating these diseases. Contact: Dr. Wen Chen, 301-496-9350,

15-AG-104 Manipulating the blood-brain-barrier to deliver CNS therapies for mental/nervous system disorders. Develop potentially useful means of CNS drug targeting and delivery systems. A variety of neuro-scientific discoveries have led to promising therapeutic strategies for treatment of severe neurological disorders. However, it remains a major hurdle to deliver potentially exciting agents such as RNA therapies, genes, critical enzymes, antibodies, other molecular entities, or cell therapies past the blood brain barrier. Contact: Dr. Steven Snyder, 301-496-9350,

15-AG-105 NIH partners in research program: Pathways for translational research. Develop strategies for dissemination of interventions with demonstrated effectiveness for translation into clinical practice by teams of academic and community research partners. This initiative will provide the knowledge to more rapidly move scientific findings into communities to improve health. Contact: Dr. Chhanda Dutta, 301-435-3048,

15-AG-106 Identification of bioactive macronutrients in the diet that impact metabolic state. Recent studies suggest that specific types of macronutrients in the diet, such as resistant starch or branched chain amino acids, may have selective effects on nutrient absorption, insulin sensitivity, and lipid metabolism. Elucidation of the metabolic impact of specific dietary components may well result in improved efficacy of lifestyle approaches to reduce obesity and metabolic diseases. This solicitation encourages pilot studies to identify specific bioactive components in the diet and study their mechanisms of action. Contact: Dr. Chhanda Dutta, 301-435-3048,

For general information on the National Institute on Aging’s implementation of NIH Challenge Grants, contact:

Director, Division of Extramural Activities
National Institute on Aging
National Institutes of Health

Page last updated Mar 26, 2009