Chad Cowan, PhD
Massachusetts General Hospital
Our research is focused on understanding the molecular underpinnings of metabolic diseases such as type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). Metabolic diseases such as T2DM and CAD are responsible for an increasingly large burden of morbidity and mortality worldwide, afflicting hundreds of millions of people. The development of new and effective treatments for these diseases requires the identification and validation in humans of novel disease mechanisms. Recent advances in human genetics have begun to explicate the heritable susceptibility to metabolic diseases; to date, genome-wide association studies in humans have identified more than 30 chromosomal loci strongly linked to T2DM, 95 loci to blood lipid levels, and 25 loci to CAD. Next-generation sequencing studies targeting the “exome” and attempting to directly identify causal genes are underway. We seek to convert novel genetic findings into the knowledge needed to develop therapies for patients. Our approach to linking human genotypes to human phenotypes has three key steps. The first is to perform human genome editing to introduce disease-associated gene mutations and DNA variants into human pluripotent stem cells (hPSCs). The second is to differentiate and engineer hPSCs into tissue types relevant to disease in order to develop ex vivo models of disease. The third is to perform functional assays in the genetically modified (and control) differentiated tissues to obtain pathophysiological insights. Once we have identified disease relevant phenotypes we plan to use our human cell-based models of disease to perform genetic and drugs screens to develop novel therapeutics.
Chad Cowan received his BA and BS, with honors, from Kansas University in 1995 and 1996. He received his PhD, from the University of Texas Southwestern at Dallas. He subsequently completed a postdoctoral fellowship with Professor Douglas Melton at Harvard University.