Gökhan S. Hotamışlıgil
Gökhan S. Hotamışlıgil, MD, PhD.
James S. Simmons Chair of Genetics & Metabolism,
Director, Sabri Ülker Center for Metabolic Research
Harvard TH Chan School of Public Health
Department of Molecular Metabolism
Assoc. Member, Harvard-MIT Broad Institute,
Harvard Stem Cell Institute, Joslin Diabetes Center
M.D. Ankara University, Ph.D. Harvard University
Dr. Hotamisligil’s research efforts focus on the molecular and genetic basis of common and complex metabolic diseases. His research examines the identity and molecular mechanisms of adaptive response systems in health and disease with a focus on metabolism. He is an internationally recognized leader with many seminal contributions including discoveries defined inflammatory origins of obesity and diabetes which are the pillars of the field of immunometabolism. His research group identified the role of endoplasmic reticulum as a key locus of metabolic and immunometabolic adaptation, identified key mechanisms that relate to ER’s metabolic functions, such as the most recent discovery of ER-bound Nrf1 as a guardian of metabolism, and identified molecules that can target ER, some of which are in clinical trials. Dr. Hotamisligil’s studies also led to the identification of new lipid and peptide hormones and their mechanisms of action. Dr. Hotamisligil pursues interdisciplinary paths and collaborations towards development of novel preventive and therapeutic strategies against chronic metabolic and inflammatory diseases. These programs have driven several drug development platforms, some currently in clinical trials. His published work has resulted in >200 scientific manuscripts which have received >70,000 citations with an h factor>100 and resulted in multiple patents.
Dr. Hotamisligil has been recognized with many fellowships and awards during his training from the Markey and Pew Foundations, and the American Diabetes Association. He’s an elected member of the Turkish Academy of Sciences and the recipient of the 2004 TUBITAK Science Award. Dr. Hotamisligil’s scholarly recognitions include the Outstanding Scientific Accomplishment Award of the American Diabetes Association, the Wertheimer Award of the International Association of Obesity, Science Award of the Vehbi Koç Foundation, Roy Greep Award for Outstanding Research of the International Endocrine Society, the International Danone Prize, and most recently the EASD-NovoNordisk Foundation Diabetes Prize for Excellence.
Further information could be obtained at:
Foundations of immunometabolism and implications for metabolic health and disease
The field of immunometabolism encompasses investigation of the regulatory pathways which control interactions between immune and metabolic responses as critical drivers of chronic disease. In the last two decades it has become clear that overlapping and redundant inflammatory pathways play pleiotropic and important roles in metabolism, and that the metabolic state is a critical determinant of immune function. Additionally, components of both the innate and adaptive immune system modulate metabolism. This is highly relevant in the context of the obesity pandemic, as obesity has been shown to drive the production of many abnormal immune mediators, and also modify the regulation of immune response signalling.
Adipocytes have been a key focus of research in this field. Studies have shown that adipocytes produce and regulate many metabolic and hormonal signals, with profound effects on systemic endocrine equilibrium. In the setting of metabolic stress and during obesity, these cells exhibit an inflammatory capacity which is key to the pathogenesis of insulin resistance and diabetes. Molecular mechanisms underlying the link between inflammatory responses and insulin action include obesity-related activation of the serine/threonine kinase, JNK. In addition, other innate immune cell types play key roles in homeostatic and adaptive settings in the adipose tissue. Recently, there has been accumulating evidence that the adaptive immune system may also contribute to insulin sensitivity,
Research has identified a critical role for circulating lipids in modulating insulin resistance. In addition, fatty acid binding proteins are central to many components of the metabolic syndrome, and play a role in modulating inflammation, especially upon exposure to lipids.
While research suggests translational potential, the complexity of networks between immunity and metabolic responses in chronic disease poses practical challenges. Despite this, therapeutic targeting indicated by experimental and genomic studies has shown promise in small clinical studies and suggests novel preventive and treatment approaches to the management of obesity, diabetes and atherosclerosis.
Prentice KJ, Saksi J, Hotamisligil GS. Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses. J Lipid Res 2019;60:734-40.
Bartelt A, Widenmaier SB, Schlein C, Johann K, Goncalves RLS, Eguchi K, Fischer AW, Parlakgül G, Snyder NA, Nguyen TB, Bruns OT, Franke D, Bawendi MG, Lynes MD, Leiria LO, Tseng YH, Inouye KE, Arruda AP, Hotamisligil GS. Brown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity. Nat Med 2018;24:292-303.