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

Assaying Protein Kinase Activity with Radiolabeled ATP.
Karra AS, Stippec S, Cobb MH J Vis Exp 2017 May 123
Correction to Insulin Promoter-Driven Gaussia Luciferase-Based Insulin Secretion Biosensor Assay for Discovery of ß-Cell Glucose-Sensing Pathways.
Kalwat MA, Wichaidit C, Nava Garcia AY, McCoy MK, McGlynn K, Hwang IH, MacMillan JB, Posner BA, Cobb MH ACS Sens 2017 Feb 2 2 316
Rasip1-Mediated Rho GTPase Signaling Regulates Blood Vessel Tubulogenesis via Non-Muscle Myosin II.
Barry DM, Koo YS, Norden PR, Wylie LA, Xu K, Wichaidit C, Azizoglu DB, Zheng Y, Cobb MH, Davis G, Cleaver O Circ. Res. 2016 Aug
Hypertension: The Missing WNKs.
Dbouk HA, Huang CL, Cobb MH Am. J. Physiol. Renal Physiol. 2016 Mar ajprenal.00358.2015
Small Cell Lung Cancer: Can recent advances in biology and molecular biology be translated into improved outcomes?
Bunn PA, Minna J, Augustyn A, Gazdar A, Ouadah Y, Krasnow MA, Berns A, Brambilla E, Rekhtman N, Massion PP, Niederst M, Peifer M, Yokota J, Govindan R, Poirier J, Byers LA, Wynes MW, McFadden D, MacPherson D, Hann CL, Farago AF, Dive C, Teicher BA, Peacock C, Johnson JE, Cobb MH, Wendel HG, Spigel D, Sage J, Yang P, Pietanza MC, Krug LM, Heymach J, Ujhazy P, Zhou C, Goto K, Dowlati A, Christensen CL, Park K, Einhorn LH, Edelman MJ, Giaccone G, Gerber DE, Salgia R, Owonikoko T, Malik S, Karachaliou N, Gandara DR, Slotman BJ, Blackhall F, Goss G, Thomas R, Rudin CM, Hirsch FR J Thorac Oncol 2016 Jan
A Kinase Divided.
Karra AS, Taylor CA, Thorne CA, Cobb MH Cancer Cell 2015 Aug 28 2 145-7
Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells.
Wauson EM, Guerra ML, Dyachok J, McGlynn K, Giles J, Ross EM, Cobb MH Mol. Endocrinol. 2015 Aug 29 8 1114-1122
ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers.
Augustyn A, Borromeo M, Wang T, Fujimoto J, Shao C, Dospoy PD, Lee V, Tan C, Sullivan JP, Larsen JE, Girard L, Behrens C, Wistuba II, Xie Y, Cobb MH, Gazdar AF, Johnson JE, Minna JD Proc. Natl. Acad. Sci. U.S.A. 2014 Sep
Ras transformation uncouples the kinesin-coordinated cellular nutrient response.
Zaganjor E, Weil LM, Gonzales JX, Minna JD, Cobb MH Proc. Natl. Acad. Sci. U.S.A. 2014 Jul 111 29 10568-73
ERK5 signaling gets XIAPed: a role for ubiquitin in the disassembly of a MAPK cascade.
Klein AM, Cobb MH EMBO J. 2014 Jul