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| Name |
Arnaout, M. Amin |
| Location
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No Affiliation |
| Primary Field
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Medical Physiology and Metabolism |
| Secondary Field
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Immunology and Inflammation |
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 Research Interests
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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 ß2 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. |
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