M. Amin Arnaout

Biosketch

M. Amin Arnaout, MD, is Professor of Medicine at Harvard Medical School, Director of the Leukocyte Biology and Inflammation Laboratory, and Physician and former Chief of the Division of Nephrology at the Massachusetts General Hospital (MGH). He earned his BS in Biology from the American University of Beirut (AUB), Lebanon, and his MD from the AUB Medical School. He was a Chief Resident in internal medicine at the AUB hospital. He briefly served as a clinical fellow in nephrology at Johns Hopkins Hospital, followed by postdoctoral fellowships in immunology and nephrology at Boston Children’s Hospital. He joined the Nephrology Division faculty at Boston Children’s Hospital in 1981. In 1988, he was recruited to MGH, becoming the Chief of the Division of Nephrology. He is an elected member of the Alpha Omega Alpha Medical Society, the American Society for Clinical Investigation, the Association of American Physicians, the American Clinical and Climatological Association, and the National Academy of Sciences. He served as Program Chair of the national meeting of the American Society of Nephrology (ASN), Chair of ASN Basic Science Committee, Council member of the International Society of Nephrology, and Board member of Keystone Symposia. Awards include an Established Investigator Award from the American Heart Association, the Ben Qurrah Award, a Presidential Medal of Excellence from the ASN, the Kuwait Prize in Applied Medical Sciences, the Homer W Smith Award from the American Society of Nephrology, and the Visionary Award for Nephrology from the National Kidney Foundation.

Research Interests

In the early 1880s, Elie Metchnikoff observed that a splinter stuck into starfish larvae was soon surrounded by mobile amebae-like cells attempting to “clear” the foreign body, leading to his Nobel-prize-winning discovery of phagocytosis. However, the receptors involved would remain unknown for almost another century. Around this time, I discovered a major leukocyte surface glycoprotein complex of 150 kDa (gp150), which was absent in leukocytes of a patient suffering from recurrent life-threatening bacterial infections. The patient’s neutrophils did not phagocytose serum-opsonized particles, but lymphocyte functions were largely intact, accounting for infrequent viral infections. These studies established the role of these receptors, named β2 integrins, in innate immunity. We then pioneered the elucidation of the 3-D structure of integrins. This work revealed the atomic basis for integrins’ divalent cation dependency and their ligand recognition. This work also identified the key nodes in the integrin structure that initiate the tightly regulated local and global conformational shifts that these receptors undergo in response to inside-out activation and ligand-induced (outside-in) proadhesive signaling, respectively. Paradoxically, these proadhesive conformational shifts are also triggered by current anti-integrin drugs developed to suppress overactive integrins in inflammatory and thrombotic diseases, leading to adverse outcomes. We are currently using structure-guided approaches to design novel integrin inhibitors that are non-agonistic and testing them in animal models.