Description of Research Expertise

I established and direct the induced Pluripotent Stem Cell (iPSC) Core facility at the University of Pennsylvania. My group has over 15 years of experience in developing human cellular models of disease using iPSCs. We have generated hiPSC lines from more than 150 normal and diseased human subjects and have characterized some of these lines extensively. We also routinely employ CRISPR/Cas9 technology to create genetic modifications in PSCs including gene reporters, gene knock-outs and single base knock-in cell lines. Another major strength of my group is establishing robust and reproducible protocols based on published literature for differentiation of PSCs into various cell lineages, which include but not limited to cardiomyocytes, hepatocytes, endothelial cells, adipocytes, skeletal muscle cells and pancreatic beta cells. Of note, I played a key role in a NIH funded project (U01 HG006398) demonstrating stem cell derived hepatocyte-like-cells (HLCs) are a powerful and relevant model for discovering and interrogating functional variants and genes contributing to complex human diseases. My Core collaborates extensively with the Penn and external stem cell research communities to facilitate research in the areas of cardiomyocyte biology, lung regeneration, hepatocyte biology, muscle regeneration and type 1 diabetes using the above-mentioned research tools that we have developed. In addition to directing the Core, I have an active research program aimed at understanding the mechanisms of action through which type 2 diabetes (T2D) risk variants and their effector genes affect disease development. To this end, we develop and validate human PSC-cell models of adipose, muscle and liver in the context of establishing robust functional assays of insulin-action, which are lacking in the field. We collaborate with others using these models to link genotype to phenotype. In addition, my lab has a particular interest in the mechanisms of action of T2D-associated variants/genes/pathways expressed and relevant in skeletal muscle using human cell models, including stem cell models that we have developed.