Massachusetts General Hospital

BiographyDr. Arnaout received his medical degree with distinction from the American University of Beirut, Lebanon. He served on the medical staff of the American University of Beirut Hospital as an intern and resident in Medicine before moving to Johns Hopkins where he completed his residency. He then moved to Harvard where he finished fellowships in immunology and nephrology at Boston's Childrens Hospital and Brigham and Women's Hospital. He currently serves as Physician and Chief of the Division of Nephrology at the Massachusetts General Hospital. 

Research

Major research activities in Dr. Arnaout's laboratory focus on dissecting the role of leukocyte adhesion in inflammation and immune injury and on elucidating the basic cellular defects in Autosomal Dominant Polycystic Kidney Disease (ADPKD).

The leukocyte integrins are cell surface receptors that mediate adhesio-dependent functions in all cell types including leukocytes, where they mediate leukocyte homing to tissues and organs a vital component of host defense against pathogens. Deregulated activation of integrins leads to pathologic inflammation. A major focus is to define the structural basis of integrin regulation, which should help in developing novel drugs to counter inflammatory diseases.

Defective regulation of tube diameter is the basic defect in ADPKD, leading to cysts in tubules and blood vessels. Mutations in one of two genes, PKD1 or PKD2 is the underlying genetic cause, but how these proteins function and are regulated is incompletely understood and is the focus of our research.

Publications

View my most recent publications at PubMed

Selected:

1. Arnaout MA, Hakim RM, Todd RF, Dana N, Colten HR.1985. Increased expression of an adhesion-promoting surface glycoprotein in the granulocytopenia of hemodialysis. N Engl J Med. 312:457.
2. Michishita M, Videm V, Arnaout MA. 1993. A novel divalent cation-binding site in the A- domain of the beta 2 integrin CR3 (CD11b/CD18) is essential for ligand binding. Cell. 72: 857.
3. Lee JO, Rieu P, Arnaout MA (Corresp. author), Liddington R. 1995. Crystal structure of the A domain of the alpha subunit of integrin CR3 (CD11b/CD18). Cell. 80:631.
4. Gonzalez-Perrett S, Kim K, Ibarra C, Damiano AE, Zotta E, Batelli M, Harris PC, Reisin IL, Arnaout MA and Cantiello HF. 2000. Polycystin-2, the protein mutated in autosomal dominant Polycystic Kidney Disease (ADPKD), is a Ca2+-permeable non-selective cation channel. Proc. Natl Acad. Sci. USA. 98:1182.
5. Xiong JP, Stehle T, Diefenbach B, Zhang R, Dunker R, Scott DL, Joachimiak A, Goodman SL, and Arnaout MA. 2001. Crystal structure of the extracellular segment of integrin aVb3. Science. Oct 12; 294:339.
6. Xiong JP, Stehle T, Zhang R, Dunker R, Joachimiak A, Frech M, Goodman SL, and Arnaout MA. 2002. Crystal structure of the extracellular domain of integrin aVb3 in complex with an Arg-Gly-Asp Ligand. Science. Apr 5; 296:151.
7. Xiong JP, Mahalingham B, Alonso JL, Borelli LA, Riu X, Zhang, Anand S, Hyman BT, Rysiok T, Muller-Pompalla D, Goodman SL, and Arnaout MA. 2009. Crystal structure of the complete integrin aVb3 ectodomain plus an alpha/beta transmembrane fragment. J Cell Biol. 186:589.