Photo of Jean J. Zhao,  PhD

Jean J. Zhao, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-2932
Fax: (617) 632-3709

Jean J. Zhao, PhD

Dana-Farber Cancer Institute


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



  • Member, Center Scientific Council

Research Abstract

Kinase signaling in cancer

We are interested in how kinases in general, and phosphatidylinositol 3-kinases (PI3K) in particular, control malignant transformation. The work of our laboratory integrates molecular biology, tissue engineering and novel mouse models of human cancer to study oncogenic alterations in kinases that are involved in primary tumor formation and metastasis. In addition to our unique genetically engineered mouse models, we have developed a number of additional experimental systems, including, synthetic human tumors, and kinome-wide libraries of activated kinases to elucidate the mechanisms by which kinases function in cancer. We hope our studies will allow us to harness the potential of these molecules as specific targets for cancer therapies.



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  • Costa C, Ebi H, Martini M, Beausoleil SA, Faber AC, Jakubik CT, Huang A, Wang Y, Nishtala M, Hall B, Rikova K, Zhao J, Hirsch E, Benes CH, Engelman JA. Measurement of PIP3 levels reveals an unexpected role for p110β in early adaptive responses to p110α-specific inhibitors in luminal breast cancer. Cancer Cell 2015; 27:97-108. PubMed
  • Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer 2014; 15:7-24. PubMed
  • Li N, Fassl A, Chick J, Inuzuka H, Li X, Mansour MR, Liu L, Wang H, King B, Shaik S, Gutierrez A, Ordureau A, Otto T, Kreslavsky T, Baitsch L, Bury L, Meyer CA, Ke N, Mulry KA, Kluk MJ, Roy M, Kim S, Zhang X, Geng Y, Zagozdzon A, Jenkinson S, Gale RE, Linch DC, Zhao JJ, Mullighan CG, Harper JW, Aster JC, Aifantis I, von Boehmer H, Gygi SP, Wei W, Look AT, Sicinski P. Cyclin C is a haploinsufficient tumour suppressor. Nat Cell Biol 2014; 16:1080-91. 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
  • Cheng H, Liu P, Zhang F, Xu E, Symonds L, Ohlson CE, Bronson RT, Maira SM, Di Tomaso E, Li J, Myers AP, Cantley LC, Mills GB, Zhao JJ. A genetic mouse model of invasive endometrial cancer driven by concurrent loss of Pten and Lkb1 Is highly responsive to mTOR inhibition. Cancer Res 2014; 74:15-23. PubMed
  • Wang Y, Lee YM, Baitsch L, Huang A, Xiang Y, Tong H, Lako A, Von T, Choi C, Lim E, Min J, Li L, Stegmeier F, Schlegel R, Eck MJ, Gray NS, Mitchison TJ, Zhao JJ. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife 2014. PubMed
  • Wang Q, Weisberg E, Zhao JJ. The gene dosage of class Ia PI3K dictates the development of PTEN hamartoma tumor syndrome. Cell Cycle 2013; 12:3589-93. PubMed
  • Hanker AB, Pfefferle AD, Balko JM, Kuba MG, Young CD, Sánchez V, Sutton CR, Cheng H, Perou CM, Zhao JJ, Cook RS, Arteaga CL. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies. Proc Natl Acad Sci U S A 2013; 110:14372-7. PubMed
  • Wang Q, Von T, Bronson R, Ruan M, Mu W, Huang A, Maira SM, Zhao JJ. Spatially distinct roles of class Ia PI3K isoforms in the development and maintenance of PTEN hamartoma tumor syndrome. Genes Dev 2013; 27:1568-80. PubMed
  • Young CD, Pfefferle AD, Owens P, Kuba MG, Rexer BN, Balko JM, Sánchez V, Cheng H, Perou CM, Zhao JJ, Cook RS, Arteaga CL. Conditional loss of ErbB3 delays mammary gland hyperplasia induced by mutant PIK3CA without affecting mammary tumor latency, gene expression or signaling. Cancer Res 2013. 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
  • 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
  • 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
  • Xu Y, Hill JW, Fukuda M, Gautron L, Sohn JW, Kim KW, Lee CE, Choi MJ, Lauzon DA, Dhillon H, Lowell BB, Zigman JM, Zhao JJ, Elmquist JK. PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis. Cell Metab 2010; 12:88-95. PubMed
  • Sopasakis VR, Liu P, Suzuki R, Kondo T, Winnay J, Tran TT, Asano T, Smyth G, Sajan MP, Farese RV, Kahn CR, Zhao JJ. Specific roles of the p110alpha isoform of phosphatidylinsositol 3-kinase in hepatic insulin signaling and metabolic regulation. Cell Metab 2010; 11:220-30. PubMed
  • Chittenden TW, Pak J, Rubio R, Cheng H, Holton K, Prendergast N, Glinskii V, Cai Y, Culhane A, Bentink S, Schwede M, Mar JC, Howe EA, Aryee M, Sultana R, Lanahan AA, Taylor JM, Holmes C, Hahn WC, Zhao JJ, Iglehart JD, Quackenbush J. Therapeutic implications of GIPC1 silencing in cancer. PLoS ONE 2011; 5:e15581. PubMed
  • 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. Endocrinology 2009; 150:4874-82. PubMed
  • Zhao JJ, Silver DP. Estrogen Receptor-Negative Breast Cancer: New Insights into Subclassification and Targeting. Clin Cancer Res 2009; 15:6309-10. PubMed
  • 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, Murty VV, Hibshoosh H, Parsons R. 3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma. Cancer Res 2009; 69:6299-306. 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
  • Jia S,Roberts TM,Zhao JJ. Should individual PI3 kinase isoforms be targeted in cancer? Curr Opin Cell Biol 2009; 21:199-208. PubMed
  • 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:ra35. 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
  • 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
  • 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; 15:3889-95. 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
  • 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
  • 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
  • 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
  • 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
  • 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.