Mechanisms of insulin sensitivity by PPAR-gamma modulation - Dr. Alex Banks

Dr. Alex Banks: Mechanisms of insulin sensitivity by PPAR-gamma modulation

Investigations in the Banks lab focus on understanding the mechanisms linking obesity with insulin resistance. The goal of this work is to provide new insights that may lead to novel therapeutic interventions. Approaches used in our work include pharmacologic and genetic approaches in mice and in human cells to mechanistically model aspects of human metabolic disease.
Dr. Banks received his PhD at Columbia University in the lab of Paul Rothman. His thesis work There he studied the role suppressors of cytokine signaling in insulin action.
Dr. Banks’ postdoctoral research was performed in labs focused on hepatic and adipose biology, respectively. In the lab of Domenico Accili at Columbia University, he found that glucose homeostasis can be controlled by protein acetylation. We identified the actions of the protein deacetylase Sirt1 on protein substrates to increase hepatic insulin sensitivity and the effects of acetylated Foxo1 as a transcriptional regulator of the rate-limiting steps controlling glucose production. These projects were significant for their use of mouse molecular genetics to clarify the mechanistic basis of disease physiology.
Dr. Banks’ postdoctoral research in the lab of Dr. Bruce Spiegelman at the Dana-Farber Cancer Institute and Harvard Medical School focused on adipose tissue biology. Obesity induced in mice by high-fat feeding activates phosphorylation of the nuclear receptor PPAR, a dominant regulator of adipogenesis and fat cell gene expression, at serine 273. We found that this phosphorylation of PPAR is blocked by anti-diabetic PPAR ligands, such as thiazolidinediones (TZDs) including rosiglitazone. This inhibition works both in vitro and in vivo, and is completely independent of classical receptor transcriptional agonism. Similarly, inhibition of PPAR phosphorylation in obese patients by rosiglitazone is very tightly associated with the anti-diabetic effects of this drug. These findings strongly suggest that phosphorylation of PPAR may be involved in the pathogenesis of insulin resistance and further present an opportunity for the development of an improved generation of anti-diabetic drugs through specific modulation of PPAR.
Dr. Banks is currently an Associate Professor of Medicine at Harvard Medical School and the Beth Israel Deaconess Medical Center in the Division of Endocrinology. He is also the director of the Energy Balance Core Facility. Their group has also developed freely available software for the analysis of indirect calorimetry and energy balance experiments. This program, CalR, has been used to analyze more than 40,000 experiments worldwide.