Skip Navigation

Thomas M. Roberts, PhD


Researcher


Researcher

  • Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School

Contact Information

  • Office Phone Number(617) 632-3049
  • Fax(617) 632-4770

Bio

Dr. Roberts received his PhD in 1976 from Harvard University, where he also completed a postdoctoral fellowship. In 1981, he joined the DFCI faculty. Dr. Roberts has played a seminal role in discovering the conceptual fabric of signaling downstream from tyrosine kinases.  His lab and that of Lewis Cantley, working together, pioneered research on PI3 kinase.  He has extended his work to stimulate the discovery of clinically useful inhibitors of oncogenic kinases.

Research

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.

Spangle JM, Roberts TM. Epigenetic regulation of RTK signaling. J Mol Med (Berl). 2017 Aug; 95(8):791-798.
View in: PubMed

Spangle JM, Roberts TM, Zhao JJ. The emerging role of PI3K/AKT-mediated epigenetic regulation in cancer. Biochim Biophys Acta. 2017 08; 1868(1):123-131.
View in: PubMed

Cizmecioglu O, Ni J, Xie S, Zhao JJ, Roberts TM. Rac1-mediated membrane raft localization of PI3K/p110ß is required for its activation by GPCRs or PTEN loss. Elife. 2016 10 04; 5.
View in: PubMed

Yuzugullu H, Von T, Thorpe LM, Walker SR, Roberts TM, Frank DA, Zhao JJ. NTRK2 activation cooperates with PTEN deficiency in T-ALL through activation of both the PI3K-AKT and JAK-STAT3 pathways. Cell Discov. 2016; 2:16030.
View in: PubMed

Rouleau C, Pores Fernando AT, Hwang JH, Faure N, Jiang T, White EA, Roberts TM, Schaffhausen BS. Transformation by Polyomavirus Middle T Antigen Involves a Unique Bimodal Interaction with the Hippo Effector YAP. J Virol. 2016 08 15; 90(16):7032-45.
View in: PubMed

Wang D, Li C, Zhang Y, Wang M, Jiang N, Xiang L, Li T, Roberts TM, Zhao JJ, Cheng H, Liu P. Combined inhibition of PI3K and PARP is effective in the treatment of ovarian cancer cells with wild-type PIK3CA genes. Gynecol Oncol. 2016 09; 142(3):548-56.
View in: PubMed

Ni J, Xie S, Ramkissoon SH, Luu V, Sun Y, Bandopadhayay P, Beroukhim R, Roberts TM, Stiles CD, Segal RA, Ligon KL, Hahn WC, Zhao JJ. Tyrosine receptor kinase B is a drug target in astrocytomas. Neuro Oncol. 2017 01; 19(1):22-30.
View in: PubMed

Spangle JM, Dreijerink KM, Groner AC, Cheng H, Ohlson CE, Reyes J, Lin CY, Bradner J, Zhao JJ, Roberts TM, Brown M. PI3K/AKT Signaling Regulates H3K4 Methylation in Breast Cancer. Cell Rep. 2016 06 21; 15(12):2692-704.
View in: PubMed

Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nat Med. 2016 07; 22(7):723-6.
View in: PubMed

Lee SJ, Kim MJ, Kwon IC, Roberts TM. Delivery strategies and potential targets for siRNA in major cancer types. Adv Drug Deliv Rev. 2016 Sep 01; 104:2-15.
View in: PubMed

Wang D, Wang M, Jiang N, Zhang Y, Bian X, Wang X, Roberts TM, Zhao JJ, Liu P, Cheng H. Effective use of PI3K inhibitor BKM120 and PARP inhibitor Olaparib to treat PIK3CA mutant ovarian cancer. Oncotarget. 2016 Mar 15; 7(11):13153-66.
View in: PubMed

Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee SH, Zhang J, Signoretti S, Loda M, Roberts TM, Zhao JJ. Corrigendum: Essential roles of PI(3)K-p110ß in cell growth, metabolism and tumorigenesis. Nature. 2016 05 12; 533(7602):278.
View in: PubMed

Wang Q, Liu P, Spangle JM, Von T, Roberts TM, Lin NU, Krop IE, Winer EP, Zhao JJ. PI3K-p110a mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers. Oncogene. 2016 Jul 07; 35(27):3607-12.
View in: PubMed

Yuzugullu H, Baitsch L, Von T, Steiner A, Tong H, Ni J, Clayton LK, Bronson R, Roberts TM, Gritsman K, Zhao JJ. A PI3K p110ß-Rac signalling loop mediates Pten-loss-induced perturbation of haematopoiesis and leukaemogenesis. Nat Commun. 2015 Oct 07; 6:8501.
View in: PubMed

Hwang JH, Pores Fernando AT, Faure N, Andrabi S, Adelmant G, Hahn WC, Marto JA, Schaffhausen BS, Roberts TM. Correction for Hwang et al., Polyomavirus small T antigen interacts with yes-associated protein to regulate cell survival and differentiation. J Virol. 2015 Jul; 89(13):6971.
View in: PubMed

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 Mar; 89(5):2857-65.
View in: 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 Oct 06; 24(19):2274-80.
View in: PubMed

Hwang JH, Pores Fernando AT, Faure N, Andrabi S, Adelmant G, Hahn WC, Marto JA, Schaffhausen BS, Roberts TM. Polyomavirus small T antigen interacts with yes-associated protein to regulate cell survival and differentiation. J Virol. 2014 Oct; 88(20):12055-64.
View in: PubMed

Pores Fernando AT, Andrabi S, Cizmecioglu O, Zhu C, Livingston DM, Higgins JM, Schaffhausen BS, Roberts TM. Polyoma small T antigen triggers cell death via mitotic catastrophe. Oncogene. 2015 May 07; 34(19):2483-92.
View in: 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 Sep; 88(18):10673-9.
View in: 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 Jul 03; 158(1):171-84.
View in: 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 Apr 29; 111(17):6395-400.
View in: 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 p110a. J Clin Invest. 2014 Apr; 124(4):1794-809.
View in: 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). Cancer Discov. 2013 Sep; 3(9):1030-43.
View in: 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. Cancer Discov. 2013 Jan; 3(1):44-51.
View in: 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(8):e44146.
View in: 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 Aug 02; 488(7409):106-10.
View in: PubMed

Utermark T, Rao T, Cheng H, Wang Q, Lee SH, Wang ZC, Iglehart JD, Roberts TM, Muller WJ, Zhao JJ. The p110a and p110ß isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis. Genes Dev. 2012 Jul 15; 26(14):1573-86.
View in: PubMed

Roberts TM, Stewart M. Role of major sperm protein (MSP) in the protrusion and retraction of Ascaris sperm. Int Rev Cell Mol Biol. 2012; 297:265-93.
View in: PubMed

Shimabukuro K, Noda N, Stewart M, Roberts TM. Reconstitution of amoeboid motility in vitro identifies a motor-independent mechanism for cell body retraction. Curr Biol. 2011 Oct 25; 21(20):1727-31.
View in: PubMed

Ilic N, Utermark T, Widlund HR, Roberts TM. PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis. Proc Natl Acad Sci U S A. 2011 Sep 13; 108(37):E699-708.
View in: PubMed

Andrabi S, Hwang JH, Choe JK, Roberts TM, Schaffhausen BS. Comparisons between murine polyomavirus and Simian virus 40 show significant differences in small T antigen function. J Virol. 2011 Oct; 85(20):10649-58.
View in: PubMed

Zhang J, Roberts TM, Shivdasani RA. Targeting PI3K signaling as a therapeutic approach for colorectal cancer. Gastroenterology. 2011 Jul; 141(1):50-61.
View in: PubMed

Lee SH, Jia S, Zhu Y, Utermark T, Signoretti S, Loda M, Schaffhausen B, Roberts TM. Transgenic expression of polyomavirus middle T antigen in the mouse prostate gives rise to carcinoma. J Virol. 2011 Jun; 85(11):5581-92.
View in: 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 Dec 16; 468(7326):968-72.
View in: 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 Jul 22; 466(7305):503-7.
View in: 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 Jun 15; 107(24):11002-7.
View in: PubMed

Ilic N, Roberts TM. Comparing the roles of the p110a and p110ß isoforms of PI3K in signaling and cancer. Curr Top Microbiol Immunol. 2010; 347:55-77.
View in: PubMed

Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug; 8(8):627-44.
View in: PubMed

Yi K, Wang X, Emmett MR, Marshall AG, Stewart M, Roberts TM. Dephosphorylation of major sperm protein (MSP) fiber protein 3 by protein phosphatase 2A during cell body retraction in the MSP-based amoeboid motility of Ascaris sperm. Mol Biol Cell. 2009 Jul; 20(14):3200-8.
View in: PubMed

Jia S, Roberts TM, Zhao JJ. Should individual PI3 kinase isoforms be targeted in cancer? Curr Opin Cell Biol. 2009 Apr; 21(2):199-208.
View in: 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. 2009 Feb 20; 384(2):304-16.
View in: 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. 2009 Jan; 83(1):117-27.
View in: 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(10):e3364.
View in: 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 Aug 15; 4(8):e1000152.
View in: 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 Aug 07; 454(7205):776-9.
View in: PubMed

Miao L, Vanderlinde O, Liu J, Grant RP, Wouterse A, Shimabukuro K, Philipse A, Stewart M, Roberts TM. The role of filament-packing dynamics in powering amoeboid cell motility. Proc Natl Acad Sci U S A. 2008 Apr 08; 105(14):5390-5.
View in: 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 Nov 27; 104(48):19011-6.
View in: 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 Oct 11; 449(7163):689-94.
View in: 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 Jun 15; 129(6):1065-79.
View in: PubMed

Williams GL, Roberts TM, Gjoerup OV. Bub1: escapades in a cellular world. Cell Cycle. 2007 Jul 15; 6(14):1699-704.
View in: 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 May 15; 104(20):8334-9.
View in: PubMed

Utermark T, Schaffhausen BS, Roberts TM, Zhao JJ. The p110alpha isoform of phosphatidylinositol 3-kinase is essential for polyomavirus middle T antigen-mediated transformation. J Virol. 2007 Jul; 81(13):7069-76.
View in: PubMed

Miao L, Yi K, Mackey JM, Roberts TM. Reconstitution in vitro of MSP-based filopodium extension in nematode sperm. Cell Motil Cytoskeleton. 2007 Apr; 64(4):235-47.
View in: PubMed

Yi K, Buttery SM, Stewart M, Roberts TM. A Ser/Thr kinase required for membrane-associated assembly of the major sperm protein motility apparatus in the amoeboid sperm of Ascaris. Mol Biol Cell. 2007 May; 18(5):1816-25.
View in: 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 Mar 23; 128(6):1077-88.
View in: PubMed

Zhao JJ, Roberts TM. PI3 kinases in cancer: from oncogene artifact to leading cancer target. Sci STKE. 2006 Dec 12; 2006(365):pe52.
View in: 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 Oct 31; 103(44):16296-300.
View in: 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 Aug 11; 281(32):23003-12.
View in: PubMed

Liu Z, Roberts TM. Human tumor mutants in the p110alpha subunit of PI3K. Cell Cycle. 2006 Apr; 5(7):675-7.
View in: 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 May; 2(5):265-73.
View in: 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 Dec 20; 102(51):18443-8.
View in: 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 Jul; 25(13):5492-8.
View in: 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 Jun 17; 121(6):837-48.
View in: PubMed

Grant RP, Buttery SM, Ekman GC, Roberts TM, Stewart M. Structure of MFP2 and its function in enhancing MSP polymerization in Ascaris sperm amoeboid motility. J Mol Biol. 2005 Apr 01; 347(3):583-95.
View in: PubMed

Rodriguez MA, LeClaire LL, Roberts TM. Preparing to move: assembly of the MSP amoeboid motility apparatus during spermiogenesis in Ascaris. Cell Motil Cytoskeleton. 2005 Apr; 60(4):191-9.
View in: PubMed

Roberts TM. Major sperm protein. Curr Biol. 2005 Mar 08; 15(5):R153.
View in: PubMed

Stewart M, Roberts TM. Cytoskeleton dynamics powers nematode sperm motility. Adv Protein Chem. 2005; 71:383-99.
View in: PubMed

Roberts TM. Comment on "observation of optical precursors in water". Phys Rev Lett. 2004 Dec 31; 93(26 Pt 1):269401.
View in: 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 Dec 15; 64(24):8867-75.
View in: 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 Jul 13; 101(28):10296-301.
View in: PubMed

Zhao JJ, Roberts TM, Hahn WC. Functional genetics and experimental models of human cancer. Trends Mol Med. 2004 Jul; 10(7):344-50.
View in: PubMed

Cotsiki M, Lock RL, Cheng Y, Williams GL, Zhao J, Perera D, Freire R, Entwistle A, Golemis EA, Roberts TM, Jat PS, Gjoerup OV. Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1. Proc Natl Acad Sci U S A. 2004 Jan 27; 101(4):947-52.
View in: 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. 2003 Dec; 4(6):463-76.
View in: PubMed

Miao L, Vanderlinde O, Stewart M, Roberts TM. Retraction in amoeboid cell motility powered by cytoskeletal dynamics. Science. 2003 Nov 21; 302(5649):1405-7.
View in: PubMed

Buttery SM, Ekman GC, Seavy M, Stewart M, Roberts TM. Dissection of the Ascaris sperm motility machinery identifies key proteins involved in major sperm protein-based amoeboid locomotion. Mol Biol Cell. 2003 Dec; 14(12):5082-8.
View in: PubMed

Hong YK, Mikami A, Schaffhausen B, Jun T, Roberts TM. A new class of mutations reveals a novel function for the original phosphatidylinositol 3-kinase binding site. Proc Natl Acad Sci U S A. 2003 Aug 05; 100(16):9434-9.
View in: PubMed

LeClaire LL, Stewart M, Roberts TM. A 48 kDa integral membrane phosphoprotein orchestrates the cytoskeletal dynamics that generate amoeboid cell motility in Ascaris sperm. J Cell Sci. 2003 Jul 01; 116(Pt 13):2655-63.
View in: 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 May; 3(5):483-95.
View in: PubMed

Baker AM, Roberts TM, Stewart M. 2.6 A resolution crystal structure of helices of the motile major sperm protein (MSP) of Caenorhabditis elegans. J Mol Biol. 2002 May 31; 319(2):491-9.
View in: PubMed

Chan J, Bayliss PE, Wood JM, Roberts TM. Dissection of angiogenic signaling in zebrafish using a chemical genetic approach. Cancer Cell. 2002 Apr; 1(3):257-67.
View in: PubMed

Luo H, Rose PE, Roberts TM, Dearolf CR. The Hopscotch Jak kinase requires the Raf pathway to promote blood cell activation and differentiation in Drosophila. Mol Genet Genomics. 2002 Mar; 267(1):57-63.
View in: PubMed

Furman C, Short SM, Subramanian RR, Zetter BR, Roberts TM. DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism. J Biol Chem. 2002 Mar 08; 277(10):7962-9.
View in: PubMed

Gjoerup O, Zaveri D, Roberts TM. Induction of p53-independent apoptosis by simian virus 40 small t antigen. J Virol. 2001 Oct; 75(19):9142-55.
View in: PubMed

Chan J, Mably JD, Serluca FC, Chen JN, Goldstein NB, Thomas MC, Cleary JA, Brennan C, Fishman MC, Roberts TM. Morphogenesis of prechordal plate and notochord requires intact Eph/ephrin B signaling. Dev Biol. 2001 Jun 15; 234(2):470-82.
View in: 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 Feb 15; 21(4):1110-6.
View in: 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 Aug 17; 19(35):3961-70.
View in: 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 Jun 16; 272(3):822-9.
View in: 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 May; 26(2):405-16.
View in: 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 Mar 28; 97(7):3336-41.
View in: 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 Jan; 74(2):864-74.
View in: PubMed

Jun T, Gjoerup O, Roberts TM. Tangled webs: evidence of cross-talk between c-Raf-1 and Akt. Sci STKE. 1999 Dec 21; 1999(13):PE1.
View in: 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 Nov 05; 274(45):32274-8.
View in: PubMed

Alberta JA, Auger KR, Batt D, Iannarelli P, Hwang G, Elliott HL, Duke R, Roberts TM, Stiles CD. Platelet-derived growth factor stimulation of monocyte chemoattractant protein-1 gene expression is mediated by transient activation of the phosphoinositide 3-kinase signal transduction pathway. J Biol Chem. 1999 Oct 22; 274(43):31062-7.
View in: PubMed

Aksoy IA, Ramsey MJ, Fruman DA, Aksoy S, Cantley LC, Tucker JD, Roberts TM. Mouse phosphoinositide 3-kinase p110alpha gene: cloning, structural organization, and localization to chromosome 3 band B. Biochem Biophys Res Commun. 1999 Aug 27; 262(2):438-42.
View in: 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 Jul; 19(7):4819-24.
View in: 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 Mar 02; 96(5):2110-5.
View in: 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 Mar; 19(3):2330-7.
View in: 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 Aug 01; 26(15):3616-8.
View in: PubMed

Batt DB, Roberts TM. Cell density modulates protein-tyrosine phosphorylation. J Biol Chem. 1998 Feb 06; 273(6):3408-14.
View in: 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 Sep; 17(9):4979-90.
View in: 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 May 01; 11(9):1098-110.
View in: 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 Apr; 18(4):553-62.
View in: 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 Mar; 17(3):1562-71.
View in: PubMed

Barber DL, Corless CN, Xia K, Roberts TM, D'Andrea AD. Erythropoietin activates Raf1 by an Shc-independent pathway in CTLL-EPO-R cells. Blood. 1997 Jan 01; 89(1):55-64.
View in: 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 Oct 15; 93(21):11681-6.
View in: 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 Sep 20; 271(38):23452-7.
View in: 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 Sep 15; 4(9):1105-14.
View in: PubMed

Corbley MJ, Cherington V, Traxler PM, Lydon NB, Roberts TM. A strategy for screening anti-tumor drugs utilizing oncogenes encoded in retroviral vectors. Int J Cancer. 1996 Jun 11; 66(6):753-9.
View in: 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 Dec; 69(12):7814-22.
View in: 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 Sep 01; 270(35):20660-7.
View in: PubMed

Agarwal S, Corbley MJ, Roberts TM. Reconstitution of signal transduction from the membrane to the nucleus in a baculovirus expression system: activation of Raf-1 leads to hypermodification of c-jun and c-fos via multiple pathways. Oncogene. 1995 Aug 03; 11(3):427-38.
View in: PubMed

Campbell KS, Auger KR, Hemmings BA, Roberts TM, Pallas DC. Identification of regions in polyomavirus middle T and small t antigens important for association with protein phosphatase 2A. J Virol. 1995 Jun; 69(6):3721-8.
View in: PubMed

Su W, Liu W, Schaffhausen BS, Roberts TM. Association of Polyomavirus middle tumor antigen with phospholipase C-gamma 1. J Biol Chem. 1995 May 26; 270(21):12331-4.
View in: PubMed

Wang J, Auger KR, Jarvis L, Shi Y, Roberts TM. Direct association of Grb2 with the p85 subunit of phosphatidylinositol 3-kinase. J Biol Chem. 1995 May 26; 270(21):12774-80.
View in: PubMed

Corbley MJ, Cherington V, Feig LA, Cooper GM, Roberts TM. Rapid regeneration of virus from cells infected with a retroviral vector. Biotechniques. 1994 Dec; 17(6):1102-3, 1106-9.
View in: PubMed

Fu H, Xia K, Pallas DC, Cui C, Conroy K, Narsimhan RP, Mamon H, Collier RJ, Roberts TM. Interaction of the protein kinase Raf-1 with 14-3-3 proteins. Science. 1994 Oct 07; 266(5182):126-9.
View in: PubMed

Pallas DC, Fu H, Haehnel LC, Weller W, Collier RJ, Roberts TM. Association of polyomavirus middle tumor antigen with 14-3-3 proteins. Science. 1994 Jul 22; 265(5171):535-7.
View in: PubMed

Campbell KS, Ogris E, Burke B, Su W, Auger KR, Druker BJ, Schaffhausen BS, Roberts TM, Pallas DC. Polyoma middle tumor antigen interacts with SHC protein via the NPTY (Asn-Pro-Thr-Tyr) motif in middle tumor antigen. Proc Natl Acad Sci U S A. 1994 Jul 05; 91(14):6344-8.
View in: PubMed

Williams NG, Roberts TM. Signal transduction pathways involving the Raf proto-oncogene. Cancer Metastasis Rev. 1994 Mar; 13(1):105-16.
View in: PubMed

Wood KW, Roberts TM. Oncogenes and protein kinases in neuronal growth-factor action. Biochim Biophys Acta. 1993 Aug 23; 1155(2):133-50.
View in: PubMed

Williams NG, Paradis H, Agarwal S, Charest DL, Pelech SL, Roberts TM. Raf-1 and p21v-ras cooperate in the activation of mitogen-activated protein kinase. Proc Natl Acad Sci U S A. 1993 Jun 15; 90(12):5772-6.
View in: PubMed

Wood KW, Qi H, D'Arcangelo G, Armstrong RC, Roberts TM, Halegoua S. The cytoplasmic raf oncogene induces a neuronal phenotype in PC12 cells: a potential role for cellular raf kinases in neuronal growth factor signal transduction. Proc Natl Acad Sci U S A. 1993 Jun 01; 90(11):5016-20.
View in: PubMed

Carrera AC, Alexandrov K, Roberts TM. The conserved lysine of the catalytic domain of protein kinases is actively involved in the phosphotransfer reaction and not required for anchoring ATP. Proc Natl Acad Sci U S A. 1993 Jan 15; 90(2):442-6.
View in: PubMed

Carrera AC, Wee SB, Roberts TM, Pardoll DM. Selective association between MHC class I-restricted T cell receptors, CDS, and activated tyrosine kinases on thymocytes undergoing positive selection. J Immunol. 1992 Nov 15; 149(10):3142-9.
View in: PubMed

Epstein RJ, Druker BJ, Roberts TM, Stiles CD. Synthetic phosphopeptide immunogens yield activation-specific antibodies to the c-erbB-2 receptor. Proc Natl Acad Sci U S A. 1992 Nov 01; 89(21):10435-9.
View in: PubMed

West AB, Roberts TM, Kolodner RD. Regulation of the reverse transcriptase of human immunodeficiency virus type 1 by dNTPs. Proc Natl Acad Sci U S A. 1992 Oct 15; 89(20):9720-4.
View in: PubMed

Druker BJ, Sibert L, Roberts TM. Polyomavirus middle T-antigen NPTY mutants. J Virol. 1992 Oct; 66(10):5770-6.
View in: PubMed

Carrera AC, Baker C, Roberts TM, Pardoll DM. Tyrosine kinase triggering in thymocytes undergoing positive selection. Eur J Immunol. 1992 Sep; 22(9):2289-94.
View in: PubMed

Williams NG, Roberts TM, Li P. Both p21ras and pp60v-src are required, but neither alone is sufficient, to activate the Raf-1 kinase. Proc Natl Acad Sci U S A. 1992 Apr 01; 89(7):2922-6.
View in: PubMed

Wood KW, Sarnecki C, Roberts TM, Blenis J. ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK. Cell. 1992 Mar 20; 68(6):1041-50.
View in: PubMed

Ling LE, Druker BJ, Cantley LC, Roberts TM. Transformation-defective mutants of polyomavirus middle T antigen associate with phosphatidylinositol 3-kinase (PI 3-kinase) but are unable to maintain wild-type levels of PI 3-kinase products in intact cells. J Virol. 1992 Mar; 66(3):1702-8.
View in: PubMed

Epstein RJ, Druker BJ, Irminger JC, Jones SD, Roberts TM, Stiles CD. Extracellular calcium mimics the actions of platelet-derived growth factor on mouse fibroblasts. Cell Growth Differ. 1992 Mar; 3(3):157-64.
View in: PubMed

Pallas DC, Weller W, Jaspers S, Miller TB, Lane WS, Roberts TM. The third subunit of protein phosphatase 2A (PP2A), a 55-kilodalton protein which is apparently substituted for by T antigens in complexes with the 36- and 63-kilodalton PP2A subunits, bears little resemblance to T antigens. J Virol. 1992 Feb; 66(2):886-93.
View in: PubMed

Ramer SE, Winkler DG, Carrera A, Roberts TM, Walsh CT. Purification and initial characterization of the lymphoid-cell protein-tyrosine kinase p56lck from a baculovirus expression system. Proc Natl Acad Sci U S A. 1991 Jul 15; 88(14):6254-8.
View in: PubMed

Longnecker R, Druker B, Roberts TM, Kieff E. An Epstein-Barr virus protein associated with cell growth transformation interacts with a tyrosine kinase. J Virol. 1991 Jul; 65(7):3681-92.
View in: PubMed

Carrera AC, Li P, Roberts TM. Characterization of an active, non-myristylated, cytoplasmic form of the lymphoid protein tyrosine kinase pp56lck. Int Immunol. 1991 Jul; 3(7):673-82.
View in: PubMed

Davis S, Lu ML, Lo SH, Lin S, Butler JA, Druker BJ, Roberts TM, An Q, Chen LB. Presence of an SH2 domain in the actin-binding protein tensin. Science. 1991 May 03; 252(5006):712-5.
View in: PubMed

Kanakura Y, Druker B, Wood KW, Mamon HJ, Okuda K, Roberts TM, Griffin JD. Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce rapid phosphorylation and activation of the proto-oncogene Raf-1 in a human factor-dependent myeloid cell line. Blood. 1991 Jan 15; 77(2):243-8.
View in: PubMed

Herrera R, Agarwal S, Walton K, Satterberg B, Distel RJ, Goodman R, Spiegelman BM, Roberts TM. A direct role for c-fos in AP-1-dependent gene transcription. Cell Growth Differ. 1990 Oct; 1(10):483-90.
View in: PubMed

Druker BJ, Ling LE, Cohen B, Roberts TM, Schaffhausen BS. A completely transformation-defective point mutant of polyomavirus middle T antigen which retains full associated phosphatidylinositol kinase activity. J Virol. 1990 Sep; 64(9):4454-61.
View in: PubMed

Epstein RJ, Druker BJ, Roberts TM, Stiles CD. Modulation of a Mr 175,000 c-neu receptor isoform in G8/DHFR cells by serum starvation. J Biol Chem. 1990 Jun 25; 265(18):10746-51.
View in: PubMed

Jin YJ, Kaplan DR, White M, Spagnoli GC, Roberts TM, Reinherz EL. Stimulation via CD3-Ti but not CD2 induces rapid tyrosine phosphorylation of a 68-kDa protein in the human Jurkat T cell line. J Immunol. 1990 Jan 15; 144(2):647-52.
View in: PubMed

Pallas DC, Shahrik LK, Martin BL, Jaspers S, Miller TB, Brautigan DL, Roberts TM. Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A. Cell. 1990 Jan 12; 60(1):167-76.
View in: PubMed

Piwnica-Worms H, Williams NG, Cheng SH, Roberts TM. Regulation of pp60c-src and its interaction with polyomavirus middle T antigen in insect cells. J Virol. 1990 Jan; 64(1):61-8.
View in: PubMed

Druker BJ, Mamon HJ, Roberts TM. Oncogenes, growth factors, and signal transduction. N Engl J Med. 1989 Nov 16; 321(20):1383-91.
View in: PubMed

Pallas DC, Morgan W, Roberts TM. The cellular proteins which can associate specifically with polyomavirus middle T antigen in human 293 cells include the major human 70-kilodalton heat shock proteins. J Virol. 1989 Nov; 63(11):4533-9.
View in: PubMed

Kaplan DR, Pallas DC, Morgan W, Schaffhausen B, Roberts TM. Mechanisms of transformation by polyoma virus middle T antigen. Biochim Biophys Acta. 1989 Feb; 948(3):345-64.
View in: PubMed

Morrison DK, Kaplan DR, Rapp U, Roberts TM. Signal transduction from membrane to cytoplasm: growth factors and membrane-bound oncogene products increase Raf-1 phosphorylation and associated protein kinase activity. Proc Natl Acad Sci U S A. 1988 Dec; 85(23):8855-9.
View in: PubMed

Pallas DC, Cherington V, Morgan W, DeAnda J, Kaplan D, Schaffhausen B, Roberts TM. Cellular proteins that associate with the middle and small T antigens of polyomavirus. J Virol. 1988 Nov; 62(11):3934-40.
View in: PubMed

Morgan WC, Kaplan DR, Pallas DC, Roberts TM. Recombinant retroviruses that transduce middle T antigen cDNAs derived from polyomavirus mutants: separation of focus formation and soft-agar growth in transformation assays and correlations with kinase activities in vitro. J Virol. 1988 Sep; 62(9):3407-14.
View in: PubMed

Figge J, Wright C, Collins CJ, Roberts TM, Livingston DM. Stringent regulation of stably integrated chloramphenicol acetyl transferase genes by E. coli lac repressor in monkey cells. Cell. 1988 Mar 11; 52(5):713-22.
View in: PubMed

Chen CF, Corbley MJ, Roberts TM, Hess P. Voltage-sensitive calcium channels in normal and transformed 3T3 fibroblasts. Science. 1988 Feb 26; 239(4843):1024-6.
View in: PubMed

Roberts TM, Kaplan D, Morgan W, Keller T, Mamon H, Piwnica-Worms H, Druker B, Cohen B, Schaffhausen B, Whitman M, et al. Tyrosine phosphorylation in signal transduction. Cold Spring Harb Symp Quant Biol. 1988; 53 Pt 1:161-71.
View in: PubMed

Morrison DK, Browning PJ, White MF, Roberts TM. Tyrosine phosphorylations in vivo associated with v-fms transformation. Mol Cell Biol. 1988 Jan; 8(1):176-85.
View in: PubMed

Feig LA, Corbley M, Pan BT, Roberts TM, Cooper GM. Structure/function analysis of ras using random mutagenesis coupled with functional screening assays. Mol Endocrinol. 1987 Feb; 1(2):127-36.
View in: PubMed

Research Departments:

Location

Dana-Farber Cancer Institute
450 Brookline Avenue
Smith 970A
Boston MA, 02215
Get Directions

Top