THE CHA LAB

Biologic sex has pleiotropic influences across multiple facets of physiology such as cognition, immunity, and metabolism. However, robust mechanistic studies evaluating the contributions of biologic sex on non-gonadal tissues to influence human health remain unclear. The Cha lab strives to understand the intersection of reproduction and metabolism, as there are clearly influences of sex on metabolic consequences across species (in the field and in the clinic) which have yet to be fundamentally resolved.

Our lab probes a unique model of extreme sex dimorphism in a fundamental aspect of metabolism: glycemia. Familial carriers of a pathogenic mutation manifest remarkably dimorphic phenotypes: men are vulnerable to dysglycemia (diabetes) while women are predisposed towards insulin-producing tumors (hypoglycemia) - two divergent diseases resulting from the same mutation, based solely on biologic sex!

We take systems biologic approaches to integrate single cell gene expression, chromatin dynamics, and classical physiologic assays to assess the transcriptional, spatial, and functional changes differentially incurred by this mutation in a robust mouse model, in cell culture systems, and in genetically modified pseudoislets derived from primary human donors. In ongoing efforts towards precision medicine, evaluating how this point mutation disrupts the metabolic landscape to produce sweeping sex differences in metabolism will uncover novel sex-driven directives and fill critical gaps in our understanding of biologic sex in metabolism.

We are proudly affiliated with: VUMC Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt Diabetes Research and Training Center, and Vanderbilt University Department of Molecular Physiology & Biophysics