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.
