Scientist Profile

• MIT, Cancer Biology
• Postdoctoral Fellow
• 1992

• Yale University, Human Genetics
• Ph.D
• 1989

• University of Pennsylvania, Neuroscience
• B.A.
• 1983

Publications & Recognition

• A chromatin-mediated reversible drug tolerant state in cancer cell subpopulations
• Cell 2010 (in press)
• Sharma, S.V., Lee, D.Y., Li, B., Quinlan, M.P., Takahashi, F., Maheswaran, S., McDermott, U., Azizian, N., Zou, L., Fischbach, M.A., Wong, K.-K., Brandstetter, K., Wittner, B., Ramaswamy, S., Classon, M., Settleman, J

• Acquired resistance of non-small cell lung cancer cells to MET kinase inhibition is mediated by a switch to epidermal growth factor receptor dependency
• Cancer Res 2010 Feb 15; 70(4): 1625-34
• McDermott U, Pusapati RV, Christensen JG, Gray NS, Settleman J
• View Abstract on PubMed

• A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival
• Cancer Cell 2009 Jun 2; 15(6): 489-500
• Singh A, Greninger P, Rhodes D, Koopman L, Violette S, Bardeesy N, Settleman J
• View Abstract on PubMed

• Ligand-dependent platelet-derived growth factor receptor (PDGFR)-alpha activation sensitizes rare lung cancer and sarcoma cells to PDGFR kinase inhibitors
• Cancer Res 2009 May 1; 69(9): 3937-46
• McDermott U, Ames RY, Iafrate AJ, Maheswaran S, Stubbs H, Greninger P, McCutcheon K, Milano R, Tam A, Lee DY, Lucien L, Brannigan BW, Ulkus LE, Ma XJ, Erlander MG, Haber DA, Sharma SV, Settleman J
• View Abstract on PubMed

• Reduced Erlotinib sensitivity of epidermal growth factor receptor-mutant non-small cell lung cancer following cisplatin exposure: a cell culture model of second-line erlotinib treatment
• Clin Cancer Res 2008 Nov 1; 14(21): 6867-76
• Chin TM, Quinlan MP, Singh A, Sequist LV, Lynch TJ, Haber DA, Sharma SV, Settleman J
• View Abstract on PubMed

• Modeling oncogene addiction using RNA interference
• Proc Natl Acad Sci USA 2008 Aug 26; 105(34): 12480-4
• Rothenberg SM, Engelman JA, Le S, Riese DJ 2nd, Haber DA, Settleman J
• View Abstract on PubMed

• p190A RhoGAP is a glycogen synthase kinase-3-beta substrate required for polarized cell migration
• J Biol Chem 2008 Jul 25; 283(30): 20978-88
• Jiang W, Betson M, Mulloy R, Foster R, Levay M, Ligeti E, Settleman J
• View Abstract on PubMed

• Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma
• Cancer Res 2008 Jun 15; 68(12): 4853-61
• Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, Dias-Santagata D, Stubbs H, Lee DY, Singh A, Drew L, Haber DA, Settleman J
• View Abstract on PubMed

• Activated Kras, but not Hras or Nras, may initiate tumors of endodermal origin via stem cell expansion
• Mol Cell Biol 2008 Apr; 28(8): 2659-74
• Quinlan MP, Quatela SE, Philips MR, Settleman J
• View Abstract on PubMed

• Detection of mutations in EGFR in circulating lung-cancer cells
• N Engl J Med 2008 Jul 24; 359(4): 366-77
• Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA
• View Abstract on PubMed

• The T790M "gatekeeper" mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor
• Mol Cancer Ther 2008 Apr; 7(4): 874-9
• Godin-Heymann N, Ulkus L, Brannigan BW, McDermott U, Lamb J, Maheswaran S, Settleman J, Haber DA
• View Abstract on PubMed

• Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors
• Cancer Res 2008 May 1; 68(9): 3389-95
• McDermott U, Iafrate AJ, Gray NS, Shioda T, Classon M, Maheswaran S, Zhou W, Choi HG, Smith SL, Dowell L, Ulkus LE, Kuhlmann G, Greninger P, Christensen JG, Haber DA, Settleman J
• View Abstract on PubMed

• Genetic interactions between Drosophila melanogaster Atg1 and paxillin reveal a role for paxillin in autophagosome formation
• Autophagy 2008 Jan 1; 4(1): 37-45
• Chen GC, Lee JY, Tang HW, Debnath J, Thomas SM, Settleman J
• View Abstract on PubMed

• Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling
• Proc Natl Acad Sci USA 2007 Dec 11; 104(50): 19936-41
• McDermott U, Sharma SV, Dowell L, Greninger P, Montagut C, Lamb J, Archibald H, Raudales R, Tam A, Lee D, Rothenberg SM, Supko JG, Sordella R, Ulkus LE, Iafrate AJ, Maheswaran S, Njauw CN, Tsao H, Drew L, Hanke JH, Ma XJ, Erlander MG, Gray NS, Haber DA, Settleman J
• View Abstract on PubMed

• A rho-binding protein kinase C-like activity is required for the function of protein kinase N in Drosophila development
• Genetics 2007 Aug; 176(4): 2201-12
• Betson M, Settleman J
• View Abstract on PubMed

• Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib
• Cancer Res 2007 Mar 1; 67(5): 2325-30
• Mulloy R, Ferrand A, Kim Y, Sordella R, Bell DW, Haber DA, Anderson KS, Settleman J
• View Abstract on PubMed

• Combinatorial treatment of non-small-cell lung cancers with gefitinib and Ad.mda-7 enhances apoptosis-induction and reverses resistance to a single therapy
• J Cell Physiol 2007 Feb; 210(2): 549-59
• Emdad L, Lebedeva IV, Su ZZ, Gupta P, Sarkar D, Settleman J, Fisher PB
• View Abstract on PubMed

• A common signaling cascade may underlie "addiction" to the Src, BCR-ABL, and EGF receptor oncogenes
• Cancer Cell 2006 Nov; 10(5): 425-35
• Sharma SV, Gajowniczek P, Way IP, Lee DY, Jiang J, Yuza Y, Classon M, Haber DA, Settleman J
• View Abstract on PubMed

• Distinct but overlapping functions for the closely related p190 RhoGAPs in neural development
• Dev Neurosci 2006; 28(6): 538-50
• Matheson SF, Hu KQ, Brouns MR, Sordella R, VanderHeide JD, Settleman J
• View Abstract on PubMed

• p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho
• Cell 2006 Dec 1; 127(5): 1027-39
• Wildenberg GA, Dohn MR, Carnahan RH, Davis MA, Lobdell NA, Settleman J, Reynolds AB
• View Abstract on PubMed

• Opposing functions of TFII-I spliced isoforms in growth factor-induced gene expression
• Mol Cell 2006 Oct 20; 24(2): 301-8
• Hakre S, Tussie-Luna MI, Ashworth T, Novina CD, Settleman J, Sharp PA, Roy AL
• View Abstract on PubMed

• Drosophila Rho-kinase (DRok) is required for tissue morphogenesis in diverse compartments of the egg chamber during oogenesis
• Dev Biol 2006 Sep 15; 297(2): 417-32
• Verdier V, Johndrow JE, Betson M, Chen GC, Hughes DA, Parkhurst SM, Settleman J
• View Abstract on PubMed

• Regulation of Rho and Rac signaling to the actin cytoskeleton by paxillin during Drosophila development
• Mol Cell Biol 2005 Feb; 25(3): 979-87
• Chen GC, Turano B, Ruest PJ, Hagel M, Settleman J, Thomas SM
• View Abstract on PubMed

• An FF domain-dependent protein interaction mediates a signaling pathway for growth factor-induced gene expression
• Mol Cell 2005 Jan 7; 17(1): 23-35
• Jiang W, Sordella R, Chen GC, Hakre S, Roy AL, Settleman J
• View Abstract on PubMed

• Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR
• Nat Genet 2005 Dec; 37(12): 1315-6
• Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, Mulloy R, Sharma SV, Brannigan BW, Mohapatra G, Settleman J, Haber DA
• View Abstract on PubMed

• The Drosophila ATM ortholog, dATM, mediates the response to ionizing radiation and to spontaneous DNA damage during development
• Curr Biol 2004 Aug 10; 14(15): 1354-9
• Song YH, Mirey G, Betson M, Haber DA, Settleman J
• View Abstract on PubMed

• Rho-LIM kinase signaling regulates ecdysone-induced gene expression and morphogenesis during Drosophila metamorphosis
• Curr Biol 2004 Feb 17; 14(4): 309-13
• Chen GC, Gajowniczek P, Settleman J
• View Abstract on PubMed

• Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways
• Science 2004 Aug 20; 305(5687): 1163-7
• Sordella R, Bell DW, Haber DA, Settleman J
• View Abstract on PubMed

• Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
• N Engl J Med 2004 May 20; 350(21): 2129-39
• Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA
• View Abstract on PubMed

• Adhesion-dependent regulation of p190RhoGAP in the developing brain by the Abl-related gene tyrosine kinase
• Curr Biol 2004 Apr 20; 14(8): 691-6
• Hernandez SE, Settleman J, Koleske AJ
• View Abstract on PubMed

• Phospholipids can switch the GTPase substrate preference of a GTPase-activating protein
• J Biol Chem 2004 Feb 13; 279(7): 5055-8
• Ligeti E, Dagher MC, Hernandez SE, Koleske AJ, Settleman J
• View Abstract on PubMed

• Specific biochemical inactivation of oncogenic Ras proteins by nucleoside diphosphate kinase
• Cancer Res 2003 Jul 15; 63(14): 4089-94
• Fischbach MA, Settleman J
• View Abstract on PubMed

• Modulation of Rho GTPase signaling regulates a switch between adipogenesis and myogenesis
• Cell 2003 Apr 18; 113(2): 147-58
• Sordella R, Jiang W, Chen GC, Curto M, Settleman J
• View Abstract on PubMed

• DOCK4, a GTPase activator, is disrupted during tumorigenesis
• Cell 2003 Mar 7; 112(5): 673-84
• Yajnik V, Paulding C, Sordella R, McClatchey AI, Saito M, Wahrer DC, Reynolds P, Bell DW, Lake R, van den Heuvel S, Settleman J, Haber DA
• View Abstract on PubMed

• Modulation of CREB activity by the Rho GTPase regulates cell and organism size during mouse embryonic development
• Dev Cell 2002 May; 2(5): 553-65
• Sordella R, Classon M, Hu KQ, Matheson SF, Brouns MR, Fine B, Zhang L, Takami H, Yamada Y, Settleman J
• View Abstract on PubMed

• p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation
• Nat Cell Biol 2001 Apr; 3(4): 361-7
• Brouns MR, Matheson SF, Settleman J
• View Abstract on PubMed

• The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development
• Development 2000 Nov; 127(22): 4891-903
• Brouns MR, Matheson SF, Hu KQ, Delalle I, Caviness VS, Silver J, Bronson RT, Settleman J
• View Abstract on PubMed

• The Drosophila Pkn protein kinase is a Rho/Rac effector target required for dorsal closure during embryogenesis
• Genes Dev 1999 May 1; 13(9): 1168-80
• Lu Y, Settleman J
• View Abstract on PubMed

• Myoblast city, the Drosophila homolog of DOCK180/CED-5, is required in a Rac signaling pathway utilized for multiple developmental processes
• Genes Dev 1998 Nov 1; 12(21): 3337-42
• Nolan KM, Barrett K, Lu Y, Hu KQ, Vincent S, Settleman J
• View Abstract on PubMed

• Evidence for distinct mechanisms of transition state stabilization of GTPases by fluoride
• Proc Natl Acad Sci USA 1998 Mar 3; 95(5): 2210-5
• Vincent S, Brouns M, Hart MJ, Settleman J
• View Abstract on PubMed

• The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation
• Cell 1997 Dec 26; 91(7): 905-15
• Barrett K, Leptin M, Settleman J
• View Abstract on PubMed

• The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization
• Mol Cell Biol 1997 Apr; 17(4): 2247-56
• Vincent S, Settleman J
• View Abstract on PubMed

• Tandem SH2 binding sites mediate the RasGAP-RhoGAP interaction: a conformational mechanism for SH3 domain regulation
• EMBO J 1997 Feb 3; 16(3): 473-83.
• Hu KQ, Settleman J
• View Abstract on PubMed

• Characterization of rho GTPase family homologues in Drosophila melanogaster: overexpressing Rho1 in retinal cells causes a late developmental defect
• EMBO J 1995 Jan 16; 14(2): 292-302
• Hariharan IK, Hu KQ, Asha H, Quintanilla A, Ezzell RM, Settleman J
• View Abstract on PubMed

• Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1
• Nature 1993 Jul 22; 364(6435): 308-13
• Zhang XF, Settleman J, Kyriakis JM, Takeuchi-Suzuki E, Elledge SJ, Marshall MS, Bruder JT, Rapp UR, Avruch J
• View Abstract on PubMed

• Association between GTPase activators for Rho and Ras families
• Nature 1992 Sep 10; 359(6391): 153-4
• Settleman J, Albright CF, Foster LC, Weinberg RA
• View Abstract on PubMed

• Molecular cloning of cDNAs encoding the GAP-associated protein p190: implications for a signaling pathway from ras to the nucleus
• Cell 1992 May 1; 69(3): 539-49
• Settleman J, Narasimhan V, Foster LC, Weinberg RA
• View Abstract on PubMed

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Awards & Honors

• 
  V Foundation Translational Cancer Research Award - 2004

• 
  Avon Foundation Award - 2003

• 
  Samuel Waxman Cancer Research Foundation Award - 2003

• 
  Bertucci Foundation Award - 2002

• 
  Saltonstall Scholar Award - 2001

• 
  American Cancer Society Junior Faculty Research Award - 1995