Ayomide Samson OLUWAJOBA
BME PhD Proposal Presentation

Date: 2026-11-04
Time: 1:00 PM-3:00 PM
Location / Meeting Link: https://emory.zoom.us/j/99869461811

Committee Members:
Ravi Kane, PhD (Advisor) Shuichi Takayama, PhD Mark Prausnitz, PhD John Blazeck, PhD Sean Palecek, PhD


Title: Engineering approaches for intrinsic control of stem cell differentiation

Abstract:
Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. In 2022, approximately 19.8 million people died from these diseases. One of the major CVDs is coronary artery disease, which can lead to myocardial infarction when blood flow to a part of the heart becomes blocked. This, in turn, damages the heart muscle and leads to the loss of cardiomyocytes. Sadly, the adult human heart has limited regenerative capacity to replace the lost cells. For this reason, researchers have investigated the potential of differentiating human induced pluripotent stem cells (hiPSCs) into cardiomyocytes (CMs) for applications in heart cell therapy biomanufacturing, cardiac research, and regenerative medicine. During hiPSC-CM differentiation, small molecules are added to the cells at selected times to regulate signaling pathways involved in cardiomyocyte development. Canonical Wnt signaling, for instance, is activated during the early differentiation stage to promote differentiation of hiPSCs from their pluripotent state into cardiac mesoderm. And later, canonical Wnt signaling is inhibited to promote the formation of cardiac progenitor cells (CPCs). Alongside the Wnt signaling pathway, another pathway that is extremely important for cardiomyocyte formation is the retinoic acid (RA) signaling pathway, and this is because it fosters the specialization of CPCs into chamber-specific cardiomyocytes. Although existing hiPSC-CM differentiation protocols can produce high proportions of cardiomyocytes, one major limitation is that the time-dependent addition of or treatment with small molecules is determined for the entire cell population rather than according to the developmental stage of individual cells. But the reality is that cells in the same population are not necessarily at the same developmental stage at the same time. Because of this lack of cell state synchronization, a treatment that is appropriate for one cell may be introduced too early or too late for another cell, potentially contributing to cell-to-cell heterogeneity and thus reducing the robustness and scalability of biomanufacturing of iPSC-derived cells. To address this problem, this research work aims to develop engineering approaches for intrinsic control of stem cell differentiation by regulating canonical Wnt and RA signaling. First, we will develop approaches for activating and inhibiting canonical Wnt signaling to control hiPSC differentiation into the cardiac mesoderm and cardiac progenitor stages, respectively. Second, we will develop approaches for cell-intrinsic activation and inhibition of RA signaling, which is involved in atrial and ventricular cardiomyocyte specification. Third, we will investigate how developmental promoters, transcriptional cascades, and feedback systems can be used to control the timing and duration of both signaling pathways. We are interested in measuring how long it takes for each promoter or cascade system to turn on and off, the time taken to reach a half-maximal response, its maximum activity, and how fast its response declines. If successfully applied during cardiac differentiation, these approaches could help reduce cell-to-cell heterogeneity and improve the production of more homogeneous atrial and ventricular cardiomyocytes for chamber-specific drug testing, disease modeling, and future applications in cardiac regenerative medicine