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Associate Professor of Medicine; Scientist, James Graham Brown Cancer Center
Research ProgramMolecular Targets
Education
Education/Training
B.Sc., University of Manchester, UK, Biochemistry & Applied Molecular Biology, 1982-1985
Ph.D., University of Manchester, UK, Molecular Oncology, 1985-1989
Postdoctoral Fellow, University of Southern California, Los Angeles, Viral Oncology, 1989-1990
Postdoctoral Fellow, La Jolla Cancer Research Foundation, California, Oncology, 1990-1992
Research and Professional Experience
1992-1995
Research Associate, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
1996-1998
Research Assistant Professor, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
1998-2006
Principal Investigator, Department of Cell and Cancer Biology, National Cancer Institute, Rockville, Maryland
2006-present
Associate Professor, Department of Medicine, University of Louisville, Kentucky
2006-present
Scientist, James Graham Brown Cancer Center, University of Louisville, Kentucky
PublicationsKhosravi-Far R, Clark GJ, Abe K, Cox AD, McLain T, Lutz RJ, Sinensky M, Der CJ. Ras (CXXX) and Rab (CC/CXC) prenylation signal sequences are unique and functionally distinct. J Biol Chem 267(34):24363-8, 1992
Clark GJ, Quilliam LA, Hisaka MM, Der CJ. Differential antagonism of Ras biological activity by catalytic and Src homology domains of Ras GTPase activation protein. Proc Natl Acad Sci USA 90(11):4887-91, 1993
Khosravi-Far R, Solski PA, Clark GJ, Kinch MS, Der CJ. Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation. Mol Cell Biol 15(11):6443-53, 1995
Clark GJ, Der CJ. Aberrant function of the Ras signal transduction pathway in human breast cancer. Breast Cancer Res Treat 35(1):133-44, 1995. Review.
Kinch MS, Clark GJ, Der CJ, Burridge K. Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia. J Cell Biol 130(2):461-71, 1995
Clark GJ, Cox AD, Graham SM, Der CJ. Biological assays for Ras transformation. Methods Enzymol 255:395-412, 1995.
Graham SM, Vojtek AB, Huff SY, Cox AD, Clark GJ, Cooper JA, Der CJ. TC21 causes transformation by Raf-independent signaling pathways. Molec Cell Biol 16(11):6132-40, 1996
Oldham SM, Clark GJ, Gangarosa LM, Coffey RJ Jr, Der CJ. Activation of the Raf-1/MAP kinase cascade is not sufficient for Ras transformation of RIE-1 epithelial cells. Proc Natl Acad Sci USA 93(14):6924-8, 1996
Clark GJ, Drugan JK, Terrell RS, Bradham C, Der CJ, Bell RM, Campbell S. Peptides containing a consensus Ras binding sequence from Raf-1 and theGTPase activating protein NF1 inhibit Ras function. Proc Natl Acad Sci USA 93(4):1577-81, 1996
Clark GJ, Kinch MS, Gilmer TM, Burridge K, Der CJ. Overexpression of the Ras-related TC21/R-Ras2 protein may contribute to the development of human breast cancers. Oncogene 12(1):169-76, 1996
Clark GJ, Drugan JK, Rossman KL, Carpenter JW, Rogers-Graham K, Fu H, Der CJ, Campbell SL. 14-3-3 zeta negatively regulates raf-1 activity by interactions with the Raf-1 cysteine-rich domain. J Biol Chem 272(34):20990-3, 1997
Clark GJ, Kinch MS, Rogers-Graham K, Sebti SM, Hamilton AD, Der CJ. The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation. J Biol Chem 272(16):10608-15, 1997
Westwick JK, Lambert QT, Clark GJ, Symons M, Van Aelst L, Pestell RG, Der CJ. Rac regulation of transformation, gene expression, and actin organization by multiple, PAK-independent pathways. Molec Cell Biol 17(3):1324-35, 1997
Clark GJ, Westwick JK, Der CJ. p120 GAP modulates Ras activation of Jun kinases and transformation. J Biol Chem 272(3):1677-81, 1997
Campbell SL, Khosravi-Far R, Rossman KL, Clark GJ, Der CJ. Increasing complexity of Ras signaling. Oncogene 17(11 Reviews):1395-413, 1998. Review.
Della Rocca GJ, Mukhin YV, Garnovskaya MN, Daaka Y, Clark GJ, Luttrell LM, Lefkowitz RJ, Raymond JR. Serotonin 5-HT1A receptor-mediated Erk activation requires calcium/calmodulin-dependent receptor endocytosis. J Biol Chem 274(8):4749-53, 1999
Vos MD, Ellis CA, Bell A, Birrer MJ, Clark GJ. Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. J Biol Chem 275(46):35669-72, 2000
Drugan JK, Rogers-Graham K, Gilmer T, Campbell S, Clark GJ. The Ras/p120 GTPase-activating protein (GAP) interaction is regulated by the p120 GAP pleckstrin homology domain. J Biol Chem 275(45):35021-7, 2000
Williams JG, Drugan JK, Yi GS, Clark GJ, Der CJ, Campbell SL. Elucidation of binding determinants and functional consequences of Ras/Raf-cysteine-rich domain interactions. J Biol Chem 275(29):22172-9, 2000
Urano J, Ellis C, Clark GJ, Tamanoi F. Characterization of Rheb functions using yeast and mammalian systems. Methods Enzymol 333:217-31, 2001
Ellis CA, Vos MD, Howell H, Vallecorsa T, Fults DW, Clark GJ. Rig is a novel Ras-related protein and potential neural tumor suppressor. Proc Natl Acad Sci USA 99(15):9876-81, 2002
Vos MD, Ellis CA, Elam C, Ulku AS, Taylor BJ, Clark GJ. RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor. J Biol Chem 278(30):28045-51, 2003
Vos MD, Martinez A, Ellis CA, Vallecorsa T, Clark GJ. The pro-apoptotic Ras effector Nore1 may serve as a Ras-regulated tumor suppressor in the lung. J Biol Chem 278(24):21938-43, 2003
Ellis CA, Vos MD, Wickline M, Riley C, Vallecorsa T, Telford WG, Zujewskil J, Clark GJ. Tamoxifen and the farnesyl transferase inhibitor FTI-277 synergize to inhibit growth in estrogen receptor-positive breast tumor cell lines. Breast Cancer Res Treat 78(1):59-67, 2003
Eckfeld K, Hesson L, Vos MD, Bieche I, Latif F, Clark GJ. RASSF4/AD037 is a potential ras effector/tumor suppressor of the RASSF family. Cancer Res 64(23):8688-93, 2004
Vos MD, Martinez A, Elam C, Dallol A, Taylor BJ, Latif F, Clark GJ. A role for the RASSF1A tumor suppressor in the regulation of tubulin polymerization and genomic stability. Cancer Res 64(12):4244-50, 2004
Dallol A, Agathanggelou A, Fenton SL, Ahmed-Choudhury J, Hesson L, Vos MD, Clark GJ, Downward J, Maher ER, Latif F. RASSF1A interacts with microtubule-associated proteins and modulates microtubule dynamics. Cancer Res 64(12):4112-6, 2004
Armesilla AL, Williams JC, Buch MH, Pickard A, Emerson M, Cartwright EJ, Oceandy D, Vos MD, Gillies S, Clark GJ, Neyses L. Novel functional interaction between the plasma membrane Ca2+ pump 4b and the proapoptotic tumor suppressor Ras-associated factor 1 (RASSF1). J Biol Chem 279(30):31318-28, 2004
Elam C, Hesson L, Vos MD, Eckfeld K, Ellis CA, Bell A, Krex D, Birrer MJ, Latif F, Clark GJ. RRP22 is a far-nesylated, nucleolar, Ras-related protein with tumor suppressor potential. Cancer Res 65(8):3117-25, 2005
Ahmed-Choudhury J, Agathanggelou A, Fenton SL, Ricketts C, Clark GJ, Maher ER, Latif F. Transcriptional regulation of cyclin A2 by RASSF1A through the enhanced binding of p120E4F to the cyclin A2 promoter. Cancer Res 65(7):2690-7, 2005
Leaner VD, Donninger H, Ellis CA, Clark GJ, Birrer MJ. p75-Ras-GRF1 is a c-Jun/AP-1 target protein: its up regulation results in increased Ras activity and is necessary for c-Jun-induced nonadherent growth of Rat1a cells. Molec Cell Biol 25(8):3324-37, 2005
Vos MD, Dallol A, Eckfeld K, Allen NP, Donninger H, Hesson LB, Calvisi D, Latif F, Clark GJ. The RASSF1A tumor suppressor activates Bax via MOAP-1. J Biol Chem 281:4557-63, 2006
Vos MD, Clark GJ. RASSF family proteins and Ras transformation. Methods Enzymol 407:311-22, 2006
Geli J, Kiss N, Lanner F, Foukakis T, Natalishvili N, Larsson O, Kogner P, Höög A, Clark GJ, Ekström TJ, Bäckdahl M, Farnebo F, Larsson C. The Ras effectors NORE1A and RASSF1A are frequently inactivated in pheochromocytoma and abdominal paraganglioma. Endocr Relat Cancer 14(1):125-34, 2007
Donninger H, Vos MD, Clark GJ. The RASSF1A tumor suppressor. J Cell Sci 120(Pt 18):3163-72, 2007. Review.
Geli J, Kogner P, Lanner F, Natalishvili N, Juhlin C, Kiss N, Clark GJ, Ekström TJ, Farnebo F, Larsson C. Assessment of NORE1A as a putative tumor suppressor in human neuroblastoma. Int J Cancer 123(2):389-94, 2008
Calvisi DF, Donninger H, Vos MD, Birrer MJ, Gordon L, Leaner V, Clark GJ. NORE1A tumor suppressor candidate modulates p21CIP1 via p53. Cancer Res 69(11):4629-37, 2009
Contact InfoCTR Building
505 South Hancock Street
Louisville, KY 40202
Phone: (502) 852-4485
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