M. Amin Arnaout, MD
Massachusetts General Hospital
The laboratory focuses on the biology and structure of integrins, a major class of cell adhesion receptors that play vital roles in normal physiology but also in disease, and on using the derived information to design and test novel anti-integrin therapeutics for common diseases affecting vital organs including the heart and kidneys.
Dr Arnaout has played a foundational role in the discovery of leukocyte integrins and their role in disease by single-handedly tracing the increased susceptibility to life-threatening bacterial infections in a patient to the absence of a novel leukocyte surface glycoprotein complex later named β2 integrins. Dr. Arnaout’s laboratory then pioneered a structure-based approach that defined the basis of integrin-ligand interactions and integrin activation, culminating in the groundbreaking elucidation of the first crystal structure of an integrin, which fundamentally reformulated the mechanistic understanding of how cells adhere and migrate, and hailed on the page of Science journal as “one of those spectacular results that will change a field", and "concomitantly advancing the field one enormous stride”.
Current work in the Arnaout laboratory addresses a) how ligand binding induces tertiary and quaternary conformational changes in the integrin leading to transmembrane links with the actin cytoskeleton that mediate cellular signals such as regulation of cell movement, cell cycle and cell differentiation. b) How structural information creates the functional diversity among the 24-known mammalian integrins, and c) how to manipulate integrin conformational states to maintain health and prevent or treat disease. Our laboratory uses a combination of crystallography, electron microscopy, biochemistry, immunology, cell biology small and large animal models of disease to relate structure to function and to design and test novel structure-guided anti-integrin therapeutics.
Dr. M. Amin Arnaout is Professor of Medicine at Harvard Medical School, Director of Leukocyte Biology and Inflammation Laboratory and the Structural Biology Program at the Massachusetts General Hospital, and Physician and Chief Emeritus of the Division of Nephrology at the Massachusetts General Hospital. Dr. Arnaout received his MD, internship and medical residency from the American University of Beirut Medical School and hospital, then completed postdoctoral fellowships in immunology and nephrology at Boston Childrens Hospital. Dr. Arnaout is board certified in internal medicine and nephrology, attends on the renal services at the Massachusetts General Hospital. He is a member of the American Society of Nephrology, the Association of American Physicians and the American Clinical and Climatological Association. He received the 2018 Homer W Smith Award presented by the American Society of Nephrology to “an individual who made outstanding contributions which fundamentally affect the science of nephrology”.
- Insights From New Study May Lead to Safer Drugs (Mass General press release)
- Mass General study finds a "Goldilocks" drug that prevents chronic kidney disease in primates — Massachusetts General Hospital News Articles, January 10, 2017
- Solving the problem of shape shifters — Harvard Gazette, 25 March 2014
- Cell Signaling: The MIDAS Touch — Nature Reviews, Molecular Cell Biology, May 2002
- Cell Adhesion Receptor Caught on Bended Knee—Harvard FOCUS, September 14, 2001
- Integrin Crystal Structure solved – https://science.sciencemag.org/content/293/5536/1743.2.full Science, 7 September 2001
- An Anthropomorphic Integrin —Science, 12 October 2001
- Integrin binding revealed—Nature Structural Biology, 2: 181,1998
- Infection Fighter Discovered—New York Times, March 26, 1993