The 15th D. Harold Copp Lecture

Metabolic Biology of the Endoplasmic Reticulum in Health and Disease

Dr. Gökhan S. Hotamişligil, M.D., Ph.D

Harvard TH Chan School of Public Health, MA, USA

Proper coordination of cellular metabolism and its integration with immune response is paramount to function of cells, organs, and organisms. The endoplasmic reticulum is the main site for protein and lipid synthesis, trafficking, and the storage of cellular calcium. Over the past two decades, Dr. Hotamişligil has worked with his group to demonstrate that ER also plays a significant role in adaptation to metabolic fluctuations, adaptation to metabolic challenges, and their integration to immune response. This important “integrated metabolic response” is disrupted by metabolic stress of chronic metabolic diseases such as obesity and diabetes in animal models and humans. Restoration of the ER adaptive folding responses by genetic or chemical means improve metabolic homeostasis in preclinical models and humans. In recent studies, they have discovered alteration in structural organization and architecture of the organelle and identified adaptive responses that emanate from the ER during metabolic stress in physiological or pathological contexts.