Swarnima Roychowdhury
BME PhD Proposal Presentation

Date: 2026-04-14
Time: 1:15 PM
Location / Meeting Link: HSRBII N600/ https://emory.zoom.us/j/7107586495?omn=99305046995 Meeting ID: 710 758 6495

Committee Members:
Michael E. Davis, PhD (Advisor); Ilanit Ronen-Itzhaki, PhD; Jennifer Kwong, PhD; Rebecca Levit, MD; David Myers, PhD


Title: Mitochondrial Integration and Bioenergetic Restoration in Cardiomyocytes via Extracellular Vesicle Transfer

Abstract:
Myocardial infarction (MI) is one of the leading causes of death worldwide and results in irreversible loss of cardiomyocytes due to progressive mitochondrial dysfunction in surviving border zone cells. This bioenergetic deficit, characterized by collapsed mitochondrial membrane potential, impaired oxidative phosphorylation, and reduced ATP production, is not addressed by current clinical therapies and contributes directly to the transition from MI to heart failure. Recent studies have explored delivering extracellular vesicles containing functional mitochondria (MEVs) as a strategy to restore cardiomyocyte bioenergetics with promising results. However, the surface proteins mediating MEV uptake in cardiomyocytes have not been identified, and the intracellular fate of EV-delivered mitochondria in cardiomyocytes remains unknown. Our lab has confirmed that bone marrow mesenchymal stem cell-derived (BMSC) MEVs carry intact, respiring mitochondria and are internalized by induced pluripotent stem cell- derived (iPSC) cardiomyocytes. We hypothesize that MSC MEV uptake in cardiomyocytes is mediated through specific EV surface receptors, and that EV-delivered mitochondrial cargo integrates with the host mitochondrial network and contributes to bioenergetic rescue. Aim 1 will characterize MSC MEV biophysical properties and mitochondrial functionality using respiratory profiling. Aim 2 will identify the surface proteins governing cardiomyocyte uptake, visualize the intracellular fate of donor mitochondrial cargo, and determine the role of mitochondrial fusion proteins in bioenergetic rescue. Aim 3 will evaluate whether intramyocardial MEV administration in a rat ischemia-reperfusion model delivers mitochondrial cargo to border zone cardiomyocytes.