Christopher Jean-Baptiste

BME PhD Proposal Presentation

Date: 2025-09-08

Time: 2pm - 4pm

Location / Meeting Link: Location: James B Williams Medical; Computer Lab 312 

Committee Members:

Laura Hansen (Advisor), Ph.D. (Georgia Institute of Technology/Emory University); William R. Taylor, M.D, Ph.D. (Georgia Institute of Technology/Emory University); Jay Patel, Ph.D. (Georgia Institute of Technology/Emory University); Hyojung Choo, Ph.D. (Emory University); Peter Thule, Ph.D. (Georgia Institute of Technology)

Title: Investigating exercise variation stimuli effects on satellite cell's angiogenic potential in peripheral artery disease

Abstract:

Cardiovascular Disease (CVD) remains a leading cause of mortality globally at a rate of 17.9 million lives lost annually. Peripheral Artery Disease (PAD) is a known precursor of CVD that follows the pathology of atherosclerotic plaque that is in the lower extremities and is highly prevalent at an estimation of greater than 200 million people worldwide. Severe PAD can evolve into irreversible damage known as Critical Limb ischemia (CLI) which is the leading cause of limb amputation. Supervised Exercise Therapy (SET) is the recommended protocol to treat intermittent claudication to reduce symptoms and eliminate progression to CLI but does not treat the underlying pathology of the disease. Although studies have shown positive results in patient feedback with SET, there is a need to understand the biological mechanisms that contribute to these results to optimize PAD treatment. Satellite Cells (SC) are quiescent skeletal muscle stem cells with a primary function to grow and repair muscle tissue. These cells can be activated through muscle injury stimulated by exercise to initiate muscle repair. The process of muscle tissue repair involves differentiation of SC to myoblasts and fusion into myofibers healthy tissue. While SCs primary role is muscle tissue regeneration, we also hypothesize that these cells have the potential to release angiogenic factors to induce revascularization, an important part of muscle repair. Current methods for SET include a walking protocol that aims to primarily treat claudication, but this protocol has not expanded and is not optimal for later stage PAD. Late-stage PAD can progress rapidly due to the microenvironment of the blood vessels affected. Approximately 40 percent of PAD patients are diagnosed with diabetes or show symptoms of hyperglycemia. The exercise regime for patients includes not only walk training, but forms of resistance training as recommended by the American Diabetes Association (ADA). The avenue of resistance training has not been well studied in cardiovascular health, and we believe investigating the effects on PAD microenvironment and SCs will provide insight on potentially optimizing PAD treatment. To investigate exercise variation effects on SC’s role in angiogenesis and arteriogenesis, we will employ complementary in vivo and in vitro approaches. Using a modified hind limb ischemia murine model that incorporates diabetic mice, we will evaluate phenotypical changes in SC populations, alterations in gene and protein expression, and the secretion of angiogenesis-related cytokines. Parallel cell-based assays will further characterize how exercise stimuli regulate SC phenotype, molecular signaling, and their capacity to promote vascular remodeling. In this proposal we aim to 1.) Determine the effects of exercise variation on SCs count and epigenetic changes and 2.) Determine the effects of exercise variation on SCs potential to induce increased levels of angiogenesis. Upon successfully validating the hypothesis, the role of SCs can improve PAD treatment by increasing blood flow to reduce CLI and cardiac events.