2023 George Lyman Duff Memorial Lecturer - Ann Marie Schmidt, MD

Dr. Ann Marie Schmidt is the Dr. Iven Young Professor of Endocrinology at the New York University Grossman School of Medicine and Director of the Diabetes Research Program at NYU Langone Health, both in New York City. Her laboratory discovered the receptor for advanced glycation end products (RAGE), a multiligand receptor for AGEs and proinflammatory ligands, such as S100/calgranulins and high mobility group box-1. Her laboratory has led studies using cellular and animal models to reveal that blockade of RAGE or genetic deletion of the receptor exerts protection in murine models of obesity, diabetes macro- and microvascular complications, and inflammation. Dr. Schmidt’s laboratory discovered that the intracellular interacting molecule of the RAGE cytoplasmic domain, Diaphanous 1 (DIAPH1), a member of the formin family, is required for RAGE signaling. Recent work implicates RAGE/DIAPH1 in the regulation of macrophage inflammation, lipid metabolism and mitochondrial function, in the context of translational science.

Dr. Schmidt’s lab is developing small molecule antagonists of the RAGE cytoplasmic domain/DIAPH1 interaction that are undergoing intensive development to maximize structure-activity relationships and pinpoint efficacies in animal models of RAGE/DIAPH1-related disorders. In early in vivo studies in mice, representatives of these molecular leads suppressed RAGE ligand-mediated inflammation, diabetes-associated kidney disease, and ischemia/reperfusion injury in the diabetic heart, and improved wound healing in diabetic mice.

The goal of her work is to define the roles for RAGE/DIAPH1 in homeostasis and disease and to drive the refinement of novel antagonists of RAGE signaling as clinical therapeutic agents for the immunometabolic disorders in which RAGE/DIAPH1 and its ligands accumulate.

Dr. Schmidt is Editor-in-Chief of Arteriosclerosis, Thrombosis and Vascular Biology.