Gordon Williams, MD

Institution: Brigham and Women's Hospital
Research: Hormonal Mechanisms of Cardiovascular Injury
Grants & Publications: Harvard Catalyst
Categories: BWH

This lab is focused on understanding the regulation of steroids in the adrenal zona glomerulosa and fasciculata/reticularis at the cell, organ, and organism levels with a specific focus on genetic determinants of hypertension and/or diabetes mellitus. A variety of techniques are used: genetic modification from siRNA of cells to specific gene knockout; ex vivo single cell studies; superfusion of cells or organs; assessing steroid enzyme function in intact cells; single cell secretion and RNA sequencing; CRISPR/Cas9 gene editing; traditional molecular tools etc. Studies of In vivo and environmental factors that influence steroid secretion include the traditional (e.g., angiotensin II, potassium, ACTH, sodium, and potassium intakes) and novel (e.g., mTOR1, sex steroids, kinins, NO, cGMP, natriuretic peptides). Of particular interest has been the effect of sex, aging and genetics on adrenal function disruptions of which lead to salt-sensitive blood pressure, insulin resistance, lipid abnormalities and diabetes. Current interest includes the epigenetic factor, lysine specific demethylase 1 (LSD1) whose genetic modification in humans leads to salt sensitive hypertension, caveolin-1 deficiency associated with insulin resistance, diabetes, hypertension and the metabolic syndrome in humans and mice, and the identification of a novel ultrashort feedback loop modifying aldosterone secretion and cross talk between the zona glomerulosa and fasciculata of the adrenal cortex.