John A. Corbett, Ph.D.

Professor of Medicine

Phone: 205-996-9546

E-mail: corbettj@uab.edu

Dr. Corbett earned his undergraduate degree in chemistry at St. Norbert College and his Ph.D. in biochemistry at Utah State University.  He then did a post-doctoral fellowship at Washington University School of Medicine (St. Louis) in the Department of Pathology.  After a brief return to Utah State University as a junior faculty member in the Department of Chemistry, he relocated to St. Louis University, joining the Department of Biochemistry and Molecular Biology as an Assistant Professor.  In 1995, he reached the rank of Professor.  In 2007, he moved to UAB, where he is Professor of Medicine and the Director of the Comprehensive Diabetes Center.  He holds joint appointments in the Departments of Cell Biology and Microbiology.  Throughout his career, Dr. Corbett has received numerous awards, including a Presidential Scholarship, the George F. Schneider Scholarship, the Greenwood Memorial Biochemistry Award and the Council for Tobacco Research Scholar Award.  He currently holds the Nancy R. and Eugene C. Gwaltney Family Endowed Chair in Juvenile Diabetes Research.

Dr. Corbett's laboratory focuses on the cell biology and biochemistry of b-cells and the role of inflammation and immunity in the development of diabetes.  He has shown that the macrophage-derived cytokine interleukin-1 (IL-1) directly impairs b-cell function by stimulating the expression of inducible nitric oxide synthase (iNOS) and the increased production of the free radical nitric oxide, resulting in the inhibition of oxidative metabolism and reduced cellular levels of ATP in islets.  Current studies also are directed at determining the mechanisms controlling the fate of the b-cells that produce nitric oxide.  Using a virus known to induce diabetes in susceptible mice, his group recently identified three novel antiviral signaling pathways that induce inflammatory gene expression in macrophages, leading to I b-cell death.  Another area of research in Dr. Corbett's laboratory is an investigation into the hypothesis that the accumulation of mitochondrial (mt) DNA mutations in b-cell increases the susceptibility of b-cells to loss of function and death during the development of type 2 diabetes.  An additional initiative in his laboratory is an investigation into the role of the gut microbiota in the development of juvenile diabetes.

Selected Publications

1.  Corbett, J.A., Lancaster, Jr., J.R., Sweetland, M.A. and McDaniel, M.L.  Interleuking 1b-induced formation of EPF-detectable iron-nitrosyl complexes in islets of Langerhans: role of nitric oxide in IL-1b-induced inhibition of insulin secretion. J. Biol. Chem. 266:21351-4, 1991.

2.  Corbett, J.A., Wang, J.L., Sweetland, M.A., Lancaster, Jr., J.R.,  and McDaniel, M.L.  1b induces the formation of nitric oxide by b cells purified from rodent islets of Langerhans: evidence for the b-cell as a source and site of action of nitric oxide. J. Clin. Invest. 90:2384-91, 1992.

3.  Corbett, J.A., Sweetland, M.A., Wang, J.L., Lancaster, Jr., J.R.,  and McDaniel, M.L.  Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans.  Proc. Natl. Acad. Sci. U.S.A. 90:1731-5, 1993.

4. Corbett, J.A., Mikhael, A., Shimizu, J., Frederick, K., Misko, T.P., McDaniel, M.L., Kanagawa, O. and Unanue, E.R.  Nitric oxide production in NOD islets-aminoguanidine sensitive and resistant stages in the immunological diabetic process.  Proc. Natl. Acad. Sci. U.S.A. 90:8992-5, 1993.

5.  Heitmeier, M.R., Scarim, A.L. and Corbett, J.A.  IFN-g increases the sensitivity of islets of Langerhans for iNOS expression induced by IL-1.  J. Biol. Chem. 272:13697-704, 1997.

6.  Arnush, M., Scarim, A.L., Heitmeier, M.R., Kelly, C.B. and Corbett, J.A.  Activation of resident islet lymphoid cells and the initiation of autoimmune diabetes: depletion of resident macrophages prevents b-cell damage. J. Immunol. 160:2684-91, 1998.

7.  Arnush, M., Manning, P.A., Marino, M.A., Heitmeier, M.R., Scarim, A.L. and Corbett, J.A.  IL-1 produced and released endogenously within human islets inhibits b-cell  function.  J. Clin. Invest. 102:516-26, 1998.

8.  Blair, L.A., Maggi, L.B., Scarim, A.L. and Corbett, J.A.  The role of interferon regulatory factor-1 in double-stranded RNA-induced iNOS expression by mouse islets.  J. Biol. Chem. 277:359-65, 2002.

9.  Steer, S.A., Scarim, A.L., Chambers, K.T. and Corbett, J.A.  Interleukin 1 stimulates islet cell death by necrosis: nitric oxide-dependent release of the immunological adjuvant HMGB1 by b-cells. PLoS Med. 3:e17, 2006.  

10.Parker, A.K., Parker, S., Yokoyama, W.M., Corbett, J.A. and Buller, R.M.L.  Induction of natural killer cell responses by Ectromelia virus controls infection.  J. Virol. 18:4070-9, 2007.