Photo of Thomas M. Roberts,  PhD

Thomas M. Roberts, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3049
Fax: (617) 632-4770

Thomas M. Roberts, PhD

Dana-Farber Cancer Institute


  • Professor, Biological Chemistry and Molecular Pharmacology, Harvard Medical School
  • Chair, Cancer Biology, Dana-Farber Cancer Institute


Research Abstract

Signaling Mechanisms and Cancer

Through the process of signal transduction, cells communicate what is happening on their surfaces to the regulatory machinery inside. This process is facilitated by a class of enzymes called kinases, which help activate specific genes in the long strands of DNA in a cell's nucleus. An overactive kinase can lead to an overactive gene and, ultimately, to cancer. Our laboratory is researching the role of these catalysts of cell growth and division and has discovered how several work. Our discoveries have become the basis of new drugs that target the actions of specific kinases. This class of drugs, called kinase inhibitors, offers extraordinary hope for the future of cancer care.

Research in the laboratory currently focuses on three areas. One is how particular kinases are involved in cancer. For instance, the kinase termed PI3K blocks the orderly process of cell death, called apoptosis. Thus, inhibiting PI3K should lead to tumor cell death. We are also exploring new ways to measure kinase activity in tumors. Every tumor is unique, with its own pattern of activated kinases. Because there are more than 600 different kinases in a given tumor, it is important to find which ones are activated so that we know which ones to inhibit. Finally, our laboratory is developing murine model systems to study kinases in tumors.

Once kinases have been pinpointed, our laboratory develops the techniques and technology that allow pharmaceutical companies to make new drugs that target them. We supply the company with the reagents necessary to test the effect of drugs on the action of tyrosine kinases. In addition, DFCI scientists have developed the means to make kinases for testing. This collaboration has led to the creation of several new drugs. In particular, the drug Gleevec has been approved by the FDA against chronic myeloid leukemia (CML). More recently we have been working with Novartis on PI3k inhibitors. PI3K inhbitors from Novartis and other companies are now entering Phase 2 trials.


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  • White EA, Kramer RE, Hwang JH, Pores Fernando AT, Naetar N, Hahn WC, Roberts TM, Schaffhausen BS, Livingston DM, Howley PM. Papillomavirus E7 oncoproteins share functions with polyomavirus small T antigens. J Virol 2015; 89:2857-65. PubMed
  • Hwang JH, Pores Fernando AT, Faure N, Andrabi S, Hahn WC, Schaffhausen BS, Roberts TM. Polyomavirus small T antigen interacts with yes-associated protein to regulate cell survival and differentiation. J Virol 2014; 88:12055-64. PubMed
  • Csibi A, Lee G, Yoon SO, Tong H, Ilter D, Elia I, Fendt SM, Roberts TM, Blenis J. The mTORC1/S6K1 Pathway Regulates Glutamine Metabolism through the eIF4B-Dependent Control of c-Myc Translation. Curr Biol 2014; 24:2274-80. PubMed
  • Utermark T, Schmit F, Lee SH, Gao X, Schaffhausen BS, Roberts TM. The phosphatidylinositol 3-kinase (PI3K) isoform dependence of tumor formation is determined by the genetic mode of PI3K pathway activation rather than by tissue type. J Virol 2014; 88:10673-9. PubMed
  • Shao DD, Xue W, Krall EB, Bhutkar A, Piccioni F, Wang X, Schinzel AC, Sood S, Rosenbluh J, Kim JW, Zwang Y, Roberts TM, Root DE, Jacks T, Hahn WC. KRAS and YAP1 converge to regulate EMT and tumor survival. Cell 2014; 158:171-84. PubMed
  • Schmit F, Utermark T, Zhang S, Wang Q, Von T, Roberts TM, Zhao JJ. PI3K isoform dependence of PTEN-deficient tumors can be altered by the genetic context. Proc Natl Acad Sci U S A 2014. PubMed
  • Gritsman K, Yuzugullu H, Von T, Yan H, Clayton L, Fritsch C, Maira SM, Hollingworth G, Choi C, Khandan T, Paktinat M, Okabe RO, Roberts TM, Zhao JJ. Hematopoiesis and RAS-driven myeloid leukemia differentially require PI3K isoform p110留. J Clin Invest 2014; 124:1794-809. PubMed
  • Korpal M, Korn JM, Gao X, Rakiec DP, Ruddy DA, Doshi S, Yuan J, Kovats SG, Kim S, Cooke VG, Monahan JE, Stegmeier F, Roberts TM, Sellers WR, Zhou W, Zhu P. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). 2013; 3:1030-43. PubMed
  • Jia S, Gao X, Lee SH, Maira SM, Wu X, Stack EC, Signoretti S, Loda M, Zhao JJ, Roberts TM. Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention. 2013; 3:44-51. PubMed
  • Pugh TJ, Weeraratne SD, Archer TC, Pomeranz Krummel DA, Auclair D, Bochicchio J, Carneiro MO, Carter SL, Cibulskis K, Erlich RL, Greulich H, Lawrence MS, Lennon NJ, McKenna A, Meldrim J, Ramos AH, Ross MG, Russ C, Shefler E, Sivachenko A, Sogoloff B, Stojanov P, Tamayo P, Mesirov JP, Amani V, Teider N, Sengupta S, Francois JP, Northcott PA, Taylor MD, Yu F, Crabtree GR, Kautzman AG, Gabriel SB, Getz G, Jäger N, Jones DT, Lichter P, Pfister SM, Roberts TM, Meyerson M, Pomeroy SL, Cho YJ. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 2012; 488:106-10. PubMed
  • Utermark T, Rao T, Cheng H, Wang Q, Lee SH, Wang ZC, Iglehart JD, Roberts TM, Muller WJ, Zhao JJ. The p110留 and p110硫 isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis. Genes Dev 2012; 26:1573-86. PubMed
  • Ni J, Liu Q, Xie S, Carlson C, Von T, Vogel K, Riddle S, Benes C, Eck M, Roberts T, Gray N, Zhao J. Functional characterization of an isoform-selective inhibitor of PI3K-p110硫 as a potential anticancer agent. 2012; 2:425-33. PubMed
  • Hofmann I, Weiss A, Elain G, Schwaederle M, Sterker D, Romanet V, Schmelzle T, Lai A, Brachmann SM, Bentires-Alj M, Roberts TM, Sellers WR, Hofmann F, Maira SM. K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo. PLoS ONE 2012; 7:e44146. PubMed
  • Lee SH, Jia S, Zhu Y, Utermark T, Signoretti S, Loda M, Schaffhausen B, Roberts TM. Transgenic expression of polyoma virus middle T antigen in the mouse prostate gives rise to carcinoma. J Virol 2011. PubMed
  • Ilić N, Roberts TM. Comparing the Roles of the p110留 and p110硫 Isoforms of PI3K in Signaling and Cancer. Curr Top Microbiol Immunol 2010; 347:55-77. PubMed
  • Johannessen CM, Boehm JS, Kim SY, Thomas SR, Wardwell L, Johnson LA, Emery CM, Stransky N, Cogdill AP, Barretina J, Caponigro G, Hieronymus H, Murray RR, Salehi-Ashtiani K, Hill DE, Vidal M, Zhao JJ, Yang X, Alkan O, Kim S, Harris JL, Wilson CJ, Myer VE, Finan PM, Root DE, Roberts TM, Golub T, Flaherty KT, Dummer R, Weber BL, Sellers WR, Schlegel R, Wargo JA, Hahn WC, Garraway LA. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 2010; 468:968-72. PubMed
  • Qi HH, Sarkissian M, Hu GQ, Wang Z, Bhattacharjee A, Gordon DB, Gonzales M, Lan F, Ongusaha PP, Huarte M, Yaghi NK, Lim H, Garcia BA, Brizuela L, Zhao K, Roberts TM, Shi Y. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature 2010; 466:503-7. PubMed
  • Lee SH, Poulogiannis G, Pyne S, Jia S, Zou L, Signoretti S, Loda M, Cantley LC, Roberts TM. A constitutively activated form of the p110beta isoform of PI3-kinase induces prostatic intraepithelial neoplasia in mice. Proc Natl Acad Sci U S A 2010; 107:11002-7. PubMed
  • Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov 2009; 8:627-44. PubMed
  • Yi K,Wang X,Emmett MR,Marshall AG,Stewart M,Roberts TM. Dephosphorylation of MSP Fiber Protein 3 (MFP3) by PP2A during Cell Body Retraction in the MSP-based Amoeboid Motility of Ascaris Sperm. Mol Biol Cell 2009; 20:3200-8. PubMed
  • Jia S,Roberts TM,Zhao JJ. Should individual PI3 kinase isoforms be targeted in cancer? Curr Opin Cell Biol 2009; 21:199-208. PubMed
  • Schaffhausen BS,Roberts TM. Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer. Virology 2008; 384:304-16. PubMed
  • Hein J,Boichuk S,Wu J,Cheng Y,Freire R,Jat PS,Roberts TM,Gjoerup OV. Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol 2008; 83:117-27. PubMed
  • Jia S,Liu Z,Zhang S,Liu P,Zhang L,Lee SH,Zhang J,Signoretti S,Loda M,Roberts TM,Zhao JJ. Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature 2008; 454:776-9. PubMed
  • Imamura S,Uchiyama J,Koshimizu E,Hanai J,Raftopoulou C,Murphey RD,Bayliss PE,Imai Y,Burns CE,Masutomi K,Gagos S,Zon LI,Roberts TM,Kishi S. A non-canonical function of zebrafish telomerase reverse transcriptase is required for developmental hematopoiesis. PLoS ONE 2008; 3:e3364. PubMed
  • Kishi S,Bayliss PE,Uchiyama J,Koshimizu E,Qi J,Nanjappa P,Imamura S,Islam A,Neuberg D,Amsterdam A,Roberts TM. The identification of zebrafish mutants showing alterations in senescence-associated biomarkers. PLoS Genet 2008; 4:e1000152. PubMed
  • Andrabi S, Gjoerup OV, Kean JA, Roberts TM, Schaffhausen B. Protein phosphatase 2A regulates life and death decisions via Akt in a context-dependent manner. Proc Natl Acad Sci U S A 2007; 104:19011-6. PubMed
  • Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 2007; 449:689-94. PubMed
  • 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; 81:7069-76. PubMed
  • Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, Sjostrom SK, Garraway LA, Weremowicz S, Richardson AL, Greulich H, Stewart CJ, Mulvey LA, Shen RR, Ambrogio L, Hirozane-Kishikawa T, Hill DE, Vidal M, Meyerson M, Grenier JK, Hinkle G, Root DE, Roberts TM, Lander ES, Polyak K, Hahn WC. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell 2007; 129:1065-79. PubMed
  • 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; 104:8334-9. PubMed
  • 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; 128:1077-88. PubMed
  • Zhao JJ, Roberts TM. PI3 kinases in cancer: from oncogene artifact to leading cancer target. Sci STKE 2006; 2006:pe52. PubMed
  • 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; 103:16296-300. PubMed
  • Lin SS, Bassik MC, Suh H, Nishino M, Arroyo JD, Hahn WC, Korsmeyer SJ, Roberts TM. PP2A regulates BCL-2 phosphorylation and proteasome-mediated degradation at the endoplasmic reticulum. J Biol Chem 2006; 281:23003-12. PubMed
  • 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; 2:265-73. PubMed
  • Liu Z, Roberts TM. Human tumor mutants in the p110alpha subunit of PI3K. Cell Cycle 2006; 5:675-7. PubMed
  • Zhao JJ, Liu Z, Wang L, Shin E, Loda MF, Roberts TM. The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells. Proc Natl Acad Sci U S A 2005; 102:18443-8. PubMed
  • Qa'dan M, Christensen KA, Zhang L, Roberts TM, Collier RJ. Membrane insertion by anthrax protective antigen in cultured cells. Mol Cell Biol 2005; 25:5492-8. PubMed
  • Westbrook TF, Martin ES, Schlabach MR, Leng Y, Liang AC, Feng B, Zhao JJ, Roberts TM, Mandel G, Hannon GJ, Depinho RA, Chin L, Elledge SJ. A genetic screen for candidate tumor suppressors identifies REST. Cell 2005; 121:837-48. PubMed
  • Berger R, Febbo PG, Majumder PK, Zhao JJ, Mukherjee S, Signoretti S, Campbell KT, Sellers WR, Roberts TM, Loda M, Golub TR, Hahn WC. Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells. Cancer Res 2004; 64:8867-75. PubMed
  • 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; 101:10296-301. PubMed
  • Zhao JJ, Roberts TM, Hahn WC. Functional genetics and experimental models of human cancer. Trends Mol Med 2004; 10:344-50. PubMed
  • Kau TR, Schroeder F, Ramaswamy S, Wojciechowski CL, Zhao JJ, Roberts TM, Clardy J, Sellers WR, Silver PA. A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells. Cancer Cell 2004; 4:463-76. PubMed
  • Zhao JJ, Gjoerup OV, Subramanian RR, Cheng Y, Chen W, Roberts TM, Hahn WC. Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase. Cancer Cell 2003; 3:483-95. PubMed
  • Chan J, Bayliss PE, Wood JM, Roberts TM. Dissection of angiogenic signaling in zebrafish using a chemical genetic approach. Cancer Cell 2002; 1:257-67. PubMed
  • Kim HA, Ratner N, Roberts TM, Stiles CD. Schwann cell proliferative responses to cAMP and Nf1 are mediated by cyclin D1. J Neurosci 2001; 21:1110-6. PubMed
  • Laham LE, Mukhopadhyay N, Roberts TM. The activation loop in Lck regulates oncogenic potential by inhibiting basal kinase activity and restricting substrate specificity. Oncogene 2000; 19:3961-70. PubMed
  • Auger KR, Wang J, Narsimhan RP, Holcombe T, Roberts TM. Constitutive cellular expression of PI 3-kinase is distinct from transient expression. Biochem Biophys Res Commun 2000; 272:822-9. PubMed
  • Kim HA, Pomeroy SL, Whoriskey W, Pawlitzky I, Benowitz LI, Sicinski P, Stiles CD, Roberts TM. A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1. Neuron 2000; 26:405-16. PubMed
  • Borghesani PR, Alt FW, Bottaro A, Davidson L, Aksoy S, Rathbun GA, Roberts TM, Swat W, Segal RA, Gu Y. Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc Natl Acad Sci U S A 2000; 97:3336-41. PubMed
  • Gjoerup O, Chao H, DeCaprio JA, Roberts TM. pRB-dependent, J domain-independent function of simian virus 40 large T antigen in override of p53 growth suppression. J Virol 2000; 74:864-74. PubMed
  • Altiok S, Batt D, Altiok N, Papautsky A, Downward J, Roberts TM, Avraham H. Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells. J Biol Chem 1999; 274:32274-8. PubMed
  • 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; 19:4819-24. PubMed
  • Ramaswamy S, Nakamura N, Vazquez F, Batt DB, Perera S, Roberts TM, Sellers WR. Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci U S A 1999; 96:2110-5. PubMed
  • King FJ, Hu E, Harris DF, Sarraf P, Spiegelman BM, Roberts TM. DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines. Mol Cell Biol 1999; 19:2330-7. PubMed
  • Liu W, Su W, Roberts TM. Discovery of estrogen-responsive genes using an improved method which combines subtractive hybridization and PCR. Nucleic Acids Res 1998; 26:3616-8. PubMed
  • Oliveira ML, Roberts TM, Druker BJ, Armelin MC. Mapping of polyomavirus middle T domain that is responsible for AP-1 activation. Oncogene 1998; 16:2975-82. PubMed
  • Brownell HL, Lydon NB, Schaefer E, Roberts TM, Raptis L. Inhibition of epidermal growth factor-mediated ERK1/2 activation by in situ electroporation of nonpermeant [(alkylamino)methyl]acrylophenone derivatives. DNA Cell Biol 1998; 17:265-74. PubMed
  • Batt DB, Roberts TM. Cell density modulates protein-tyrosine phosphorylation. J Biol Chem 1998; 273:3408-14. PubMed
  • Culler. Serine 257 phosphorylation regulates association of polyomavirus middle T antigen with 14-3-3 proteins. J Virol 1998; 72:558-63. PubMed
  • Sheng Q, Denis D, Ratnofsky M, Roberts TM, DeCaprio JA, Schaffhausen B. The DnaJ domain of polyomavirus large T antigen is required to regulate Rb family tumor suppressor function. J Virol 1997; 71:9410-6. PubMed
  • Stubdal H, Zalvide J, Campbell KS, Schweitzer C, Roberts TM, DeCaprio JA. Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of simian virus 40 large T antigen. Mol Cell Biol 1997; 17:4979-90. PubMed
  • Chang HW, Aoki M, Fruman D, Auger KR, Bellacosa A, Tsichlis PN, Cantley LC, Roberts TM, Vogt PK. Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase. Science 1997; 276:1848-50. PubMed
  • 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; 11:1098-110. PubMed
  • Williams BP, Park JK, Alberta JA, Muhlebach SG, Hwang GY, Roberts TM, Stiles CD. A PDGF-regulated immediate early gene response initiates neuronal differentiation in ventricular zone progenitor cells. Neuron 1997; 18:553-62. PubMed
  • Luo H, Rose P, Barber D, Hanratty WP, Lee S, Roberts TM, D'Andrea AD, Dearolf CR. Mutation in the Jak kinase JH2 domain hyperactivates Drosophila and mammalian Jak-Stat pathways. Mol Cell Biol 1997; 17:1562-71. PubMed
  • Johnstone RW, See RH, Sells SF, Wang J, Muthukkumar S, Englert C, Haber DA, Licht JD, Sugrue SP, Roberts T, Rangnekar VM, Shi Y. A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1. Mol Cell Biol 1996; 16:6945-56. PubMed
  • Xia K, Mukhopadhyay NK, Inhorn RC, Barber DL, Rose PE, Lee RS, Narsimhan RP, D'Andrea AD, Griffin JD, Roberts TM. The cytokine-activated tyrosine kinase JAK2 activates Raf-1 in a p21ras-dependent manner. Proc Natl Acad Sci U S A 1996; 93:11681-6. PubMed
  • Auger KR, Songyang Z, Lo SH, Roberts TM, Chen LB. Platelet-derived growth factor-induced formation of tensin and phosphoinositide 3-kinase complexes. J Biol Chem 1996; 271:23452-7. PubMed
  • Nam HJ, Haser WG, Roberts TM, Frederick CA. Intramolecular interactions of the regulatory domains of the Bcr-Abl kinase reveal a novel control mechanism. Structure 1996; 4:1105-14. PubMed
  • Jung JU, Lang SM, Jun T, Roberts TM, Veillette A, Desrosiers RC. Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. J Virol 1995; 69:7814-22. PubMed
  • Jung JU, Lang SM, Friedrich U, Jun T, Roberts TM, Desrosiers RC, Biesinger B. Identification of Lck-binding elements in tip of herpesvirus saimiri. J Biol Chem 1995; 270:20660-7. PubMed