DF/HCC Program Affiliation

Member, Prostate Cancer Program
Member, Cancer Cell Biology Program
Member, Breast Cancer Program

Research Abstract

Research in the Roberts laboratory is centered on the molecular mechanisms of signal transduction in response to activated tyrosine kinases. We pioneered structure/function studies on tyrosine kinases showing how tyrosine kinases such as pp60c-src are themselves regulated by tyrosine phosphorylation. The first definitive work on PI3'kinase was done by this lab in collaboration with that of Cantley and Schaffhausen. Similarly our lab first showed that the serine threonine kinase Raf-1 was regulated by mitogens and then helped to elucidate the pathway from p21ras to Raf to MAP kinases. More recently we first characterized the novel binding site used by the SHC protooncogene product to bind to receptors, and pointed out the interaction of the 14-3-3 molecules with key signal transducers. Finally we and our collaborators in the DeCaprio and Schaffhausen labs have showed how virus-encoded tumor antigens use molecular chaperones to direct the ubiquitin dependent degradation of phosphorylated forms of cell cycle control proteins. Currently we are working to clone and characterize new signaling molecules. The lab specializes in developing technologies for the study of signaling. These include the first synthetic gene for a tyrosine kinase (lck), the most widely used antiphosphotyrosine antibody, and the use of the zebrafish system for studying the role of signaling molecules in development.

Publications

• Gjoerup OV, Wu J, Chandler-Militello D, Williams GL, Zhao J, Schaffhausen B, Jat PS, Roberts TM. Surveillance mechanism linking Bub1 loss to the p53 pathway. Proc Natl Acad Sci U S A 2007 May 8;
  PMID: 17488820
• Utermark T, Schaffhausen BS, Roberts TM, Zhao JJ. The p110{alpha} isoform of PI3K is essential for polyoma middle T antigen mediated transformation. J Virol 2007 Apr 18;
  PMID: 17442716
• Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell 2007 Mar 23; 128(6):1077-88
  PMID: 17320160
• Zhao JJ, Roberts TM. PI3 kinases in cancer: from oncogene artifact to leading cancer target. Sci STKE 2006 Dec 12; 2006(365):pe52
  PMID: 17164467
• Zhao JJ, Cheng H, Jia S, Wang L, Gjoerup OV, Mikami A, Roberts TM. The p110alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation. Proc Natl Acad Sci U S A 2006 Oct 31; 103(44):16296-300
  PMID: 17060635
• Liu Z, Roberts TM. Human tumor mutants in the p110alpha subunit of PI3K. Cell Cycle 2006 Apr; 5(7):675-7
  PMID: 16627990
• Bayliss PE, Bellavance KL, Whitehead GG, Abrams JM, Aegerter S, Robbins HS, Cowan DB, Keating MT, O'Reilly T, Wood JM, Roberts TM, Chan J. Chemical modulation of receptor signaling inhibits regenerative angiogenesis in adult zebrafish. Nat Chem Biol 2006 May; 2(5):265-73
  PMID: 16565716
• Qa'dan M, Christensen KA, Zhang L, Roberts TM, Collier RJ. Membrane insertion by anthrax protective antigen in cultured cells. Mol Cell Biol 2005 Jul; 25(13):5492-8
  PMID: 15964805
• Zhang L, Gjoerup O, Roberts TM. The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling. Proc Natl Acad Sci U S A 2004 Jul 13; 101(28):10296-301
  PMID: 15240878
• Xia K, Lee RS, Narsimhan RP, Mukhopadhyay NK, Neel BG, Roberts TM. Tyrosine phosphorylation of the proto-oncoprotein Raf-1 is regulated by Raf-1 itself and the phosphatase Cdc25A. Mol Cell Biol 1999 Jul; 19(7):4819-24
  PMID: 10373531
• Campbell KS, Mullane KP, Aksoy IA, Stubdal H, Zalvide J, Pipas JM, Silver PA, Roberts TM, Schaffhausen BS, DeCaprio JA. DnaJ/hsp40 chaperone domain of SV40 large T antigen promotes efficient viral DNA replication. Genes Dev 1997 May 1; 11(9):1098-110
  PMID: 9159391