Matt Robeson

PhD Proposal Presentation

Date: May 5th

Time: 8-10 AM (Atlanta), 8-10 PM (Beijing)

Bluejeans Link:  https://bluejeans.com/974758086

Thesis Advisor:

Michael E Davis, PhD

Thesis Committee:

Michael E Davis, PhD (Advisor)

Josh Maxwell, PhD

Steven Goudy, MD

Jianzhong Xi, PhD (PKU)
Rui-Ping Xiao, MD, PhD (PKU)

Title:     Engineered Notch Signaling in 2D and 3D in Cardiac Repair and Remodeling

Abstract:     Damage to the myocardium following myocardial infarction is a leading cause of heart failure. Though advances in interventional cardiology in recent decades have improved the acute survival rates for MI patients, many of these patients go on to develop heart failure, sometimes years later. The limited availability of transplants has led to the development of therapies aimed at augmenting the heart’s own endogenous capacity for repair, including stem cell, biomaterial, and molecular therapies. The aim of this study is further development of two such therapies. C-kit+ cardiac progenitor cells (CPCs) are an endogenous population of stem cells within the heart that contribute to injury response and remodeling. However, without the right biochemical cues directing differentiation of these cells, their efficacy is limited. Here we describe the engineering of a bioactive hydrogel capable of directing CPC differentiation through the Notch signaling pathway. Additionally, we explore a molecular therapy for heart failure known as MG53. MG53 is a striated muscle protein involved in both cardioprotective signaling and membrane repair. However, MG53 also has deleterious effects, contributing to fibrosis and insulin resistance within the heart. A mutant form, MG53-C14A was recently shown to retain cardioprotective benefits without the deleterious effects associated with insulin resistance. Here, we aim to characterize the effects of MG53-C14A on cardiac fibrosis through cross-talk between the Notch and JAK/STAT signaling pathways.