Biography

Melanie Cobb received her undergraduate degree in biochemistry from the University of Chicago and her PhD in biological chemistry from Washington University in St. Louis in the laboratory of Garland Marshall. Following postdoctoral work with Ora Rosen at the Albert Einstein College of Medicine in New York, she joined the Department of Pharmacology at UT Southwestern Medical Center in Dallas where she is currently a Professor and the holder of the Jane and Bill Browning, Jr Chair in Medical Science. Her interests are in cellular regulatory mechanisms.

We study how cells sense and respond to hormones, nutrients, stress and developmental signals in their environment to elucidate regulatory mechanisms with a focus on protein kinase signaling pathways as the targets of these cell stimuli. We are interested in the functions of ERK1/2 MAP kinases in nutrient-sensing pathways, notably in pancreatic beta cells and many cancers, particularly nonsmall cell lung cancer and small cell lung cancer (SCLC). ERK1/2 interfere with survival of SCLC and we are investigating the molecular mechanisms. In studying insulin gene transcription, we determined that ERK1/2 and other regulatory components of the ERK cascade, including the activating MAP2Ks and the phosphatase calcineurin, bind to the insulin gene promoter enabling transcriptional regulation by phosphorylation/dephosphorylation to occur routinely on chromatin. Among other kinase targets, we are investigating mechanisms of action of WNKs, the only protein kinases in the eukaryotic kinase superfamily with a unique position of the catalytic lysine. Altered expression of WNK1 is the cause of Gordon’s syndrome, a rare form of hypertension, and also hereditary and sensory neuropathy type 2. WNK1 forms a complex with the protein kinases OSR1 and SPAK (STK39) and we have identified several ion channels and other proteins regulated by this pathway. Their additional actions on trafficking, the cytoskeleton, and migration in endothelial cells begin to build a picture of the breadth of their functions.

Education

Graduate School
Washington University (1976)

Research Interest

  • cancer biology
  • protein kinase structure/function
  • regulation of nutrient responses
  • signal transduction mechanisms
  • vesicular trafficking

Publications

Featured Publications LegendFeatured Publications

Ras regulates kinesin 13 family members to control cell invasion pathways in cancer.
E. Zaganjor, J.K. Osborne, L. Weil, L.A. Diaz-Martinez, J.X. Gonzales, S.M. Singel, J.E. Larsen, L. Girard, J.D. Minna, M.H. Cobb Oncogene 2013 in press
Interactions with WNK (With No Lysine) Family Members Regulate Oxidative Stress Response 1 and Ion Co-transporter Activity.
Sengupta S, Tu SW, Wedin K, Earnest S, Stippec S, Luby-Phelps K, Cobb MH J. Biol. Chem. 2012 Nov 287 45 37868-79
Signal control through Raf: in sickness and in health.
Osborne JK, Zaganjor E, Cobb MH Cell Res. 2012 Jan 22 1 14-22
Interactions with with no lysine (K) (WNK) family members regulate oxidative stress response 1 (OSR1) and ion cotransporter activity
S. Sengupta, S.-W. Tu, K. Wedin, S. Earnest, S. Stippec, K. Luby-Phelps, M.H. Cobb J Biol Chem 2012 37868-37879
A small molecule differentiation inducer increases insulin production by pancreatic ß cells.
Dioum EM, Osborne JK, Goetsch S, Russell J, Schneider JW, Cobb MH Proc. Natl. Acad. Sci. U.S.A. 2011 Dec 108 51 20713-8
WNK1 is required for mitosis and abscission.
Tu SW, Bugde A, Luby-Phelps K, Cobb MH Proc. Natl. Acad. Sci. U.S.A. 2011 Jan 108 4 1385-90
Exposing contingency plans for kinase networks.
Klein AM, Dioum EM, Cobb MH Cell 2010 Dec 143 6 867-9
Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members.
Heise CJ, Xu BE, Deaton SL, Cha SK, Cheng CJ, Earnest S, Sengupta S, Juang YC, Stippec S, Xu Y, Zhao Y, Huang CL, Cobb MH J. Biol. Chem. 2010 Aug 285 33 25161-7
Regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) expression by interleukin-1 beta in pancreatic beta cells.
Shao C, Lawrence MC, Cobb MH J. Biol. Chem. 2010 Jun 285 26 19710-9
Regulation of CCAAT-enhancer binding protein homologous protein (CHOP) expression by interleukin 1 beta in pancreatic beta cells.
C. Shao, M.C. Lawrence and M.H. Cobb. J. Biol. Chem 2010 285 19710-19719