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.
- Graduate School
- Washington University (1976)
- cancer biology
- protein kinase structure/function
- regulation of nutrient responses
- signal transduction mechanisms
- vesicular trafficking
- G protein-coupled receptors and the regulation of autophagy.
- Wauson EM, Dbouk HA, Ghosh AB, Cobb MH Trends Endocrinol. Metab. 2014 May 25 5 274-282
- NeuroD1 mediates nicotine-induced migration and invasion via regulation of the nicotinic acetylcholine receptor subunits in a subset of neural and neuroendocrine carcinomas.
- Osborne JK, Guerra ML, Gonzales JX, McMillan EA, Minna JD, Cobb MH Mol. Biol. Cell 2014 Apr
- Regulation of OSR1 and the sodium, potassium, two chloride cotransporter by convergent signals.
- Sengupta S, Lorente-Rodríguez A, Earnest S, Stippec S, Guo X, Trudgian DC, Mirzaei H, Cobb MH Proc. Natl. Acad. Sci. U.S.A. 2013 Nov 110 47 18826-31
- Ras regulates kinesin 13 family members to control cell migration pathways in transformed human bronchial epithelial cells.
- Zaganjor E, Osborne JK, Weil LM, Diaz-Martinez LA, Gonzales JX, Singel SM, Larsen JE, Girard L, Minna JD, Cobb MH Oncogene 2013 Nov
- Minireview: nutrient sensing by g protein-coupled receptors.
- Wauson EM, Lorente-Rodríguez A, Cobb MH Mol. Endocrinol. 2013 Aug 27 8 1188-97
- Off-Target Effects of MEK Inhibitors.
- Wauson EM, Guerra ML, Barylko B, Albanesi JP, Cobb MH Biochemistry 2013 Jul
- NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM.
- Osborne JK, Larsen JE, Shields MD, Gonzales JX, Shames DS, Sato M, Kulkarni A, Wistuba II, Girard L, Minna JD, Cobb MH Proc. Natl. Acad. Sci. U.S.A. 2013 Apr 110 16 6524-9
- Amino acid regulation of autophagy through the GPCR TAS1R1-TAS1R3.
- Wauson EM, Zaganjor E, Cobb MH Autophagy 2013 Mar 9 3 418-9
- Chromatin-tethered MAPKs.
- Klein AM, Zaganjor E, Cobb MH Curr. Opin. Cell Biol. 2013 Feb
- NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition.
- Osborne JK, Larsen JE, Gonzales JX, Shames DS, Sato M, Wistuba II, Girard L, Minna JD, Cobb MH Oncogenesis 2013 2 e63