DF/HCC Program Affiliation

Prostate Cancer
Breast Cancer

Research Abstract

We are interested in how kinases in general, and phosphatidylinositol 3-kinases (PI3K) in particular, control malignant transformation. We have developed a number of experimental systems, including knockout and transgeneic mouse models, synthetic human tumors, and kinome-wide libraries of gain/loss-of-function kinases to understand how kinases work, in order to harness their potential as targets for cancer therapies.

Publications

• 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.
  19644473
• Cheng H, Liu P, Wang ZC, Zou L, Santiago S, Garbitt V, Gjoerup OV, Iglehart JD, Miron A, Richardson AL, Hahn WC, Zhao JJ.SIK1 couples LKB1 to p53-dependent anoikis and suppresses metastasis.Sci Signal 2009;2(80):ra35.
  19622832
• 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 7;454(7205):776-9.
  18594509
• 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, Rober
  17574021
• 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.
  17060635
• 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.
  16339315
• Zhao JJ, Silver DP.Estrogen Receptor-Negative Breast Cancer: New Insights into Subclassification and Targeting.Clin Cancer Res 2009 Oct 13.
  19825953
• Hill JW, Xu Y, Preitner F, Fukuda M, Cho YR, Luo J, Balthasar N, Coppari R, Cantley LC, Kahn BB, Zhao JJ, Elmquist JK.Phosphatidyl Inositol 3-Kinase Signaling in Hypothalamic Proopiomelanocortin Neurons Contributes to the Regulation of Glucose Homeostasis
  19819947
• Maurer M, Su T, Saal LH, Koujak S, Hopkins BD, Barkley CR, Wu J, Nandula S, Dutta B, Xie Y, Chin YR, Kim DI, Ferris JS, Gruvberger-Saal SK, Laakso M, Wang X, Memeo L, Rojtman A, Matos T, Yu JS, Cordon-Cardo C, Isola J, Terry MB, Toker A, Mills GB, Zhao JJ
  19602588
• 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.
  19200708
• 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.
  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.
  17442716
• He Q, Zhu X, Shi M, Zhao B, Zhao J, Zhang S, Miao J.Novel morpholin-3-one derivatives induced apoptosis and elevated the level of P53 and Fas in A549 lung cancer cells.Bioorg Med Chem 2007 Jun 1;15(11):3889-95.
  17395471
• Zhao JJ, Roberts TM.PI3 kinases in cancer: from oncogene artifact to leading cancer target.Sci STKE 2006 Dec 12;2006(365):pe52.
  17164467
• 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.
  15960972
• 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):8867-7
  15604246
• Zhao JJ, Roberts TM, Hahn WC.Functional genetics and experimental models of human cancer.Trends Mol Med 2004 Jul;10(7):344-50.
  15242683
• 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 Ce
  14706338
• 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.
  12781366