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Principal Investigator: Sheila Hegde
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $195,480
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY
This K23 application supports Dr. Sheila Hegde, a highly promising cardiac imager and early-stage
investigator who is committed to investigating the underlying mechanisms by which physical activity (PA)
favorably impacts the risk of heart failure (HF) in late-life. Her long-term goal is to be an independent
investigator studying modifiable biomarkers of aging and HF risk that will ultimately inform therapeutic
intervention. The overall scientific objective of this proposal is to identify biologic pathways underlying the
beneficial effects of PA on cardiac function, functional capacity, and HF risk using high dimensional ‘-omic’
data. The main hypothesis is that PA delays age-related changes in cardiac structure and function and
mitigates HF risk through biologic pathways that can be identified through high throughput circulating
proteomic profiling. The specific aims are to: 1) Employ high-throughput plasma proteomics and genomic data
to identify novel molecular pathways underlying longitudinal PA-related changes in cardiovascular structure
and function and incident HF (NHLBI ARIC cohort); and 2) Identify molecular pathways underlying the
beneficial effect of a structured PA intervention on functional capacity with the use of plasma proteomics in
older sedentary adults at high risk of HF. (Brigham and Women’s Hospital-based cohort). These aims will also
serve as a vehicle to achieve the following career and learning objectives: 1) Attain advanced skills in novel,
data science driven methods for high-dimensional data, particularly in proteomics analysis; and 2) Develop the
necessary skills to design, implement, and conduct a clinical trial in order to transition to an independent
clinical investigator. These objectives will be accomplished through: 1) structured interactions with a
committed and expert multidisciplinary panel of mentors and advisors; 2) focused didactic coursework in study
design and statistical approaches relevant to ‘-omic’ data; and 3) progressive participation in multi-institutional
working groups and committees for national multicenter studies, dedicated mini-courses and meetings relevant
to PA and multi ‘-omic’ analyses, and national cardiovascular professional organizations. These activities will
also act as a framework to grow her leadership skills and to develop external collaborations.
The results of the proposed early career development award will provide further insight into the
underlying cardiovascular mechanisms by which physical activity impacts age-related changes in cardiac
structure and function, functional capacity, and heart failure (HF) risk and serve as the necessary foundation
for Dr. Hegde to transition to an independent investigator.
Terms: <21+ years old><ATF6><ATF6 gene><Activating Transcription Factor 6><Activities of Daily Living><Activities of everyday life><Adult><Adult Human><Affect><Age><Atherosclerosis Risk in Communities><Biological><Biological Markers><Blood Plasma><Cardiac><Cardiac rehabilitation><Cardiopulmonary><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular Physiology><Cardiovascular system><Career Development Awards><Career Development Awards and Programs><Career Development Programs K-Series><Clinic><Clinical Investigator><Clinical Trials><Clinical Trials Design><Collaborations><Data><Data Analyses><Data Analysis><Data Science><Dedications><Development><Dose><EFRAC><Echocardiogram><Echocardiography><Ejection Fraction><Event><Exclusion><Exercise><Exercise Test><Foundations><Funding><Future><Genetic><Goals><Grant><Heart Vascular><Heart failure><Hospitals><Impairment><Individual><Institution><Intervention><Intervention Strategies><Intervention Studies><Investigators><K-Awards><K-Series Research Career Programs><LVEF><Leadership><Learning><Left><Left Ventricular Ejection Fraction><Leisures><Life Style Modification><Link><Long-term cohort study><Longitudinal cohort study><Longterm cohort study><Measures><Mendelian randomization><Mentors><Methods><Molecular><Morbidity><Morbidity - disease rate><Multi-center studies><Multicenter Studies><NHLBI><National Heart, Lung, and Blood Institute><Observation in research><Outcome><Pathway interactions><Patient Recruitments><Physical activity><Plasma><Plasma Proteins><Plasma Serum><Preventative intervention><Prevention><Professional Organizations><Proteins><Proteomics><Public Health><QOL><Quality of life><Randomized><Recommendation><Research><Research Career Program><Research Design><Research Personnel><Researchers><Reticuloendothelial System, Serum, Plasma><Risk><STC gene><STC protein><STC1><STC1 gene><Stanniocalcin 1><Structure><Study Type><Therapeutic Intervention><Time><Training><Transthoracic Echocardiography><VO2 max><VO2max><Ventricular><Woman><adjudication><adjudicative process and procedure><adulthood><age associated><age associated alterations><age associated changes><age associated effects><age correlated><age correlated alterations><age correlated changes><age dependent><age dependent alterations><age dependent changes><age effect><age linked><age related><age related alterations><age related changes><age related effects><age specific><age specific alterations><age specific changes><ages><aging biological marker><aging biomarker><aging effect><aging marker><alterations with age><aptamer><bio-markers><biologic><biologic marker><biomarker><cardiac failure><cardiac function><cardiac rehab><cardiorespiratory fitness><cardiorespiratory health><cardiovascular function><career><changes with age><circulatory system><cohort><daily living function><daily living functionality><data interpretation><design><designing><developmental><exercise intervention><exercise training><experience><function of the heart><functional ability><functional capacity><genomic data><genomic data-set><genomic dataset><heart failure and reduced ejection fraction><heart failure with reduced ejection fraction><heart function><heart rehabilitation><heart sonography><high dimensional data><high dimensionality><high risk><imager><impact of age><improved><influence of age><insight><interest><intervention for prevention><intervention research><intervention therapy><interventional research><interventional strategy><interventional study><interventions research><late life><lifestyle modification><maximal oxygen uptake><meeting><meetings><mortality><multidimensional data><multidimensional datasets><multidisciplinary><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><older adult><older adulthood><participant recruitment><pathway><pharmacologic><physical activity intervention><preservation><prevent><preventing><prevention intervention><preventional intervention strategy><preventive intervention><professional association><professional membership><professional society><programs><prospective><protective effect><proteomic signature><randomisation><randomization><randomly assigned><sedentary><skills><stanniocalcin><study design><work group><working group>