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_zhao@dfci.harvard.edu

Jean J. Zhao, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

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

DF/HCC PROGRAM AFFILIATION

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.

Publications from Harvard Catalyst Profiles

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  • Liu W, Wang Y, Bozi LHM, Fischer P, Jedrychowski MP, Xiao H, Wu T, Darabedian N, He X, Mills EL, Burger N, Shin S, Reddy A, Sprenger HG, Tran N, Winther S, Hinshaw SM, Shen J, Seo HS, Song K, Xu AZ, Sebastian L, Zhao J, Dhe-Paganon S, Che J, Gygi SP, Arthanari H, Chouchani ET. Lactate regulates cell cycle by remodeling the anaphase promoting complex. Nature 2023. PubMed
  • Lin Z, Wang Q, Jiang T, Wang W, Zhao JJ. Targeting tumor-associated macrophages with STING agonism improves the antitumor efficacy of osimertinib in a mouse model of mutant lung cancer. 2023; 14:1077203. PubMed
  • Ding L, Wang Q, Martincuks A, Kearns MJ, Jiang T, Lin Z, Cheng X, Qian C, Xie S, Kim HJ, Launonen IM, Färkkilä A, Roberts TM, Freeman GJ, Liu JF, Konstantinopoulos PA, Matulonis U, Yu H, Zhao JJ. STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer. J Immunother Cancer 2023. PubMed
  • Kabraji S, Ni J, Sammons S, Li T, Van Swearingen AED, Wang Y, Pereslete A, Hsu L, DiPiro PJ, Lascola C, Moore H, Hughes M, Raghavendra AS, Gule-Monroe M, Murthy RK, Winer EP, Anders CK, Zhao JJ, Lin NU. Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases. Clin Cancer Res 2022. PubMed
  • Wang D, Wang Q, Wang Y, Chen P, Lu X, Jia F, Sun Y, Sun T, Zhang L, Che F, He J, Lian L, Morano G, Shen M, Ren M, Dong SS, Zhao JJ, Zhang K. Targeting oncogenic KRAS with molecular brush-conjugated antisense oligonucleotides. Proc Natl Acad Sci U S A 2022; 119:e2113180119. PubMed
  • Wang Q, Bergholz JS, Ding L, Lin Z, Kabraji SK, Hughes ME, He X, Xie S, Jiang T, Wang W, Zoeller JJ, Kim HJ, Roberts TM, Konstantinopoulos PA, Matulonis UA, Dillon DA, Winer EP, Lin NU, Zhao JJ. STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer. Nat Commun 2022; 13:3022. PubMed
  • Goel S, Bergholz JS, Zhao JJ. Targeting CDK4 and CDK6 in cancer. Nat Rev Cancer 2022. PubMed
  • Gao X, Wang Y, Ribeiro CF, Manokaran C, Chang H, Von T, Rodrigues S, Cizmecioglu O, Jia S, Korpal M, Korn JM, Wang Z, Schmit F, Jiang L, Pagliarini R, Yang Y, Sethi I, Signoretti S, Yuan GC, Loda M, Zhao JJ, Roberts TM. Blocking PI3K p110β Attenuates Development of PTEN-Deficient Castration-Resistant Prostate Cancer. Mol Cancer Res 2022. PubMed
  • Chen P, Wang D, Wang Y, Zhang L, Wang Q, Liu L, Li J, Sun X, Ren M, Wang R, Fang Y, Zhao JJ, Zhang K. Maximizing TLR9 Activation in Cancer Immunotherapy with Dual-Adjuvanted Spherical Nucleic Acids. Nano Lett 2022; 22:4058-4066. PubMed
  • Li Y, Pazyra-Murphy MF, Avizonis D, de Sá Tavares Russo M, Tang S, Chen CY, Hsueh YP, Bergholz JS, Jiang T, Zhao JJ, Zhu J, Ko KW, Milbrandt J, DiAntonio A, Segal RA. Sarm1 activation produces cADPR to increase intra-axonal Ca++ and promote axon degeneration in PIPN. J Cell Biol 2022. PubMed
  • Hu SH, He XD, Nie J, Hou JL, Wu J, Liu XY, Wei Y, Tang HR, Sun WX, Zhou SX, Yuan YY, An YP, Yan GQ, Lin Y, Lin PC, Zhao JJ, Ye ML, Zhao JY, Xu W, Zhao SM. Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake. Cell Rep 2022; 38:110509. PubMed
  • Xie S, Ni J, Guo H, Luu V, Wang Y, Zhao JJ, Roberts TM. The role of the PIK3CA gene in the development and aging of the brain. Sci Rep 2021; 11:291. PubMed
  • Watt AC, Cejas P, DeCristo MJ, Metzger-Filho O, Lam EYN, Qiu X, BrinJones H, Kesten N, Coulson R, Font-Tello A, Lim K, Vadhi R, Daniels VW, Montero J, Taing L, Meyer CA, Gilan O, Bell CC, Korthauer KD, Giambartolomei C, Pasaniuc B, Seo JH, Freedman ML, Ma C, Ellis MJ, Krop I, Winer E, Letai A, Brown M, Dawson MA, Long HW, Zhao JJ, Goel S. CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity. 2021; 2:34-48. PubMed
  • Spangle JM, Von T, Pavlick DC, Khotimsky A, Zhao JJ, Roberts TM. PIK3CA C-terminal frameshift mutations are novel oncogenic events that sensitize tumors to PI3K-α inhibition. Proc Natl Acad Sci U S A 2020; 117:24427-24433. PubMed
  • Xie S, Ni J, McFaline-Figueroa JR, Wang Y, Bronson RT, Ligon KL, Wen PY, Roberts TM, Zhao JJ. Divergent Roles of PI3K Isoforms in PTEN-Deficient Glioblastomas. Cell Rep 2020; 32:108196. PubMed
  • Bergholz JS, Wang Q, Kabraji S, Zhao JJ. Integrating immunotherapy and targeted therapy in cancer treatment: Mechanistic insights and clinical implications. Clin Cancer Res 2020. PubMed
  • Ngo B, Kim E, Osorio-Vasquez V, Doll S, Bustraan S, Liang RJ, Luengo A, Davidson SM, Ali A, Ferraro GB, Fischer GM, Eskandari R, Kang DS, Ni J, Plasger A, Rajasekhar VK, Kastenhuber ER, Bacha S, Sriram RK, Stein BD, Bakhoum SF, Snuderl M, Cotzia P, Healey JH, Mainolfi N, Suri V, Friedman A, Manfredi M, Sabatini DM, Jones DR, Yu M, Zhao JJ, Jain RK, Keshari KR, Davies MA, Vander Heiden MG, Hernando E, Mann M, Cantley LC, Pacold ME. Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition. 2020. PubMed
  • Bhola PD, Ahmed E, Guerriero JL, Sicinska E, Su E, Lavrova E, Ni J, Chipashvili O, Hagan T, Pioso MS, McQueeney K, Ng K, Aguirre AJ, Cleary JM, Cocozziello D, Sotayo A, Ryan J, Zhao JJ, Letai A. High-throughput dynamic BH3 profiling may quickly and accurately predict effective therapies in solid tumors. Sci Signal 2020. PubMed
  • Fassl A, Brain C, Abu-Remaileh M, Stukan I, Butter D, Stepien P, Feit AS, Bergholz J, Michowski W, Otto T, Sheng Q, Loo A, Michael W, Tiedt R, DeAngelis C, Schiff R, Jiang B, Jovanovic B, Nowak K, Ericsson M, Cameron M, Gray N, Dillon D, Zhao JJ, Sabatini DM, Jeselsohn R, Brown M, Polyak K, Sicinski P. Increased lysosomal biomass is responsible for the resistance of triple-negative breast cancers to CDK4/6 inhibition. Sci Adv 2020; 6:eabb2210. PubMed
  • Sun B, Mason S, Wilson RC, Hazard SE, Wang Y, Fang R, Wang Q, Yeh ES, Yang M, Roberts TM, Zhao JJ, Wang Q. Inhibition of the transcriptional kinase CDK7 overcomes therapeutic resistance in HER2-positive breast cancers. Oncogene 2019. PubMed
  • Hemmati S, Sinclair T, Tong M, Bartholdy B, Okabe RO, Ames K, Ostrodka L, Haque T, Kaur I, Mills TS, Agarwal A, Pietras EM, Zhao JJ, Roberts TM, Gritsman K. PI3 kinase alpha and delta promote hematopoietic stem cell activation. JCI Insight 2019. PubMed
  • Wen PY, Touat M, Alexander BM, Mellinghoff IK, Ramkissoon S, McCluskey CS, Pelton K, Haidar S, Basu SS, Gaffey SC, Brown LE, Martinez-Ledesma JE, Wu S, Kim J, Wei W, Park MA, Huse JT, Kuhn JG, Rinne ML, Colman H, Agar NYR, Omuro AM, DeAngelis LM, Gilbert MR, de Groot JF, Cloughesy TF, Chi AS, Roberts TM, Zhao JJ, Lee EQ, Nayak L, Heath JR, Horky LL, Batchelor TT, Beroukhim R, Chang SM, Ligon AH, Dunn IF, Koul D, Young GS, Prados MD, Reardon DA, Yung WKA, Ligon KL. Buparlisib in Patients With Recurrent Glioblastoma Harboring Phosphatidylinositol 3-Kinase Pathway Activation: An Open-Label, Multicenter, Multi-Arm, Phase II Trial. J Clin Oncol 2019; 37:741-750. PubMed
  • Liu Z, Wang Y, Kabraji S, Xie S, Pan P, Liu Z, Ni J, Zhao JJ. Improving orthotopic mouse models of patient-derived breast cancer brain metastases by a modified intracarotid injection method. Sci Rep 2019; 9:622. PubMed
  • Ding L, Kim HJ, Wang Q, Kearns M, Jiang T, Ohlson CE, Li BB, Xie S, Liu JF, Stover EH, Howitt BE, Bronson RT, Lazo S, Roberts TM, Freeman GJ, Konstantinopoulos PA, Matulonis UA, Zhao JJ. PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer. Cell Rep 2018; 25:2972-2980.e5. PubMed
  • Wang Y, Li BB, Li J, Roberts TM, Zhao JJ. A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells. iScience 2018; 9:149-160. PubMed
  • Pan P, Chen J, Li X, Li M, Yu H, Zhao JJ, Ni J, Wang X, Sun H, Tian S, Zhu F, Liu F, Huang Y, Hou T. Structure-Based Drug Design and Identification of HO-Soluble and Low Toxic Hexacyclic Camptothecin Derivatives with Improved Efficacy in Cancer and Lethal Inflammation Models in Vivo. J Med Chem 2018. PubMed
  • Li AG, Murphy EC, Culhane AC, Powell E, Wang H, Bronson RT, Von T, Giobbie-Hurder A, Gelman RS, Briggs KJ, Piwnica-Worms H, Zhao JJ, Kung AL, Kaelin WG, Livingston DM. BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1α activation. Proc Natl Acad Sci U S A 2018. PubMed
  • Li J, Choi PS, Chaffer CL, Labella K, Hwang JH, Giacomelli AO, Kim JW, Ilic N, Doench JG, Ly SH, Dai C, Hagel K, Hong AL, Gjoerup O, Goel S, Ge JY, Root DE, Zhao JJ, Brooks AN, Weinberg RA, Hahn WC. An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer. Elife 2018. PubMed
  • Goel S, DeCristo MJ, McAllister SS, Zhao JJ. CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest. Trends Cell Biol 2018. PubMed
  • Sun B, Wang G, Liu H, Liu P, Twal WO, Cheung H, Carroll SL, Ethier SP, Mevers EE, Clardy J, Roberts T, Chen C, Li Q, Wang L, Yang M, Zhao JJ, Wang Q. Oridonin inhibits aberrant AKT activation in breast cancer. 2018; 9:23878-23889. PubMed
  • Bergholz JS, Roberts TM, Zhao JJ. Isoform-Selective Phosphatidylinositol 3-Kinase Inhibition in Cancer. J Clin Oncol 2018. PubMed
  • Jeselsohn R, Bergholz JS, Pun M, Cornwell M, Liu W, Nardone A, Xiao T, Li W, Qiu X, Buchwalter G, Feiglin A, Abell-Hart K, Fei T, Rao P, Long H, Kwiatkowski N, Zhang T, Gray N, Melchers D, Houtman R, Liu XS, Cohen O, Wagle N, Winer EP, Zhao J, Brown M. Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations. Cancer Cell 2018; 33:173-186.e5. PubMed
  • Zhou Z, Li M, Zhang L, Zhao H, Şahin Ö, Chen J, Zhao JJ, Songyang Z, Yu D. Oncogenic kinase-induced PKM2 tyrosine 105 phosphorylation converts non-oncogenic PKM2 to a tumor promoter and induces cancer stem-like cells. Cancer Res 2018. PubMed
  • Kabraji S, Ni J, Lin NU, Xie S, Winer EP, Zhao JJ. Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain? Clin Cancer Res 2018. PubMed
  • Li BB, Qian C, Gameiro PA, Liu CC, Jiang T, Roberts TM, Struhl K, Zhao JJ. Targeted profiling of RNA translation reveals mTOR-4EBP1/2-independent translation regulation of mRNAs encoding ribosomal proteins. Proc Natl Acad Sci U S A 2018; 115:E9325-E9332. PubMed
  • Garcia-Galiano D, Borges BC, Donato J, Allen SJ, Bellefontaine N, Wang M, Zhao JJ, Kozloff KM, Hill JW, Elias CF. PI3Kα inactivation in leptin receptor cells increases leptin sensitivity but disrupts growth and reproduction. JCI Insight 2017. PubMed
  • Venkatesh HS, Tam LT, Woo PJ, Lennon J, Nagaraja S, Gillespie SM, Ni J, Duveau DY, Morris PJ, Zhao JJ, Thomas CJ, Monje M. Targeting neuronal activity-regulated neuroligin-3 dependency in high-grade glioma. Nature 2017; 549:533-537. PubMed
  • Huang HT, Seo HS, Zhang T, Wang Y, Jiang B, Li Q, Buckley DL, Nabet B, Roberts JM, Paulk J, Dastjerdi S, Winter GE, McLauchlan H, Moran J, Bradner JE, Eck MJ, Dhe-Paganon S, Zhao JJ, Gray NS. MELK is not necessary for the proliferation of basal-like breast cancer cells. Elife 2017. PubMed
  • Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, Khan N, Ubellacker JM, Xie S, Metzger-Filho O, Hoog J, Ellis MJ, Ma CX, Ramm S, Krop IE, Winer EP, Roberts TM, Kim HJ, McAllister SS, Zhao JJ. CDK4/6 inhibition triggers anti-tumour immunity. Nature 2017; 548:471-475. PubMed
  • Zhang J, Gao X, Schmit F, Adelmant G, Eck MJ, Marto JA, Zhao JJ, Roberts TM. CRKL Mediates p110β-Dependent PI3K Signaling in PTEN-Deficient Cancer Cells. Cell Rep 2017; 20:549-557. PubMed
  • Thorpe LM, Spangle JM, Ohlson CE, Cheng H, Roberts TM, Cantley LC, Zhao JJ. PI3K-p110α mediates the oncogenic activity induced by loss of the novel tumor suppressor PI3K-p85α. Proc Natl Acad Sci U S A 2017; 114:7095-7100. PubMed
  • Hydbring P, Wang Y, Fassl A, Li X, Matia V, Otto T, Choi YJ, Sweeney KE, Suski JM, Yin H, Bogorad RL, Goel S, Yuzugullu H, Kauffman KJ, Yang J, Jin C, Li Y, Floris D, Swanson R, Ng K, Sicinska E, Anders L, Zhao JJ, Polyak K, Anderson DG, Li C, Sicinski P. Cell-Cycle-Targeting MicroRNAs as Therapeutic Tools against Refractory Cancers. Cancer Cell 2017; 31:576-590.e8. PubMed
  • Spangle JM, Roberts TM, Zhao JJ. The emerging role of PI3K/AKT-mediated epigenetic regulation in cancer. Biochim Biophys Acta 2017; 1868:123-131. 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. 2017. PubMed
  • Mathew G, Hannan A, Hertzler-Schaefer K, Wang F, Feng GS, Zhong J, Zhao JJ, Downward J, Zhang X. Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor. Proc Natl Acad Sci U S A 2016; 113:13156-13161. PubMed
  • Cizmecioglu O, Ni J, Xie S, Zhao JJ, Roberts TM. Rac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss. Elife 2016. 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; 142:548-56. PubMed
  • Wang Y, Begley M, Li Q, Huang HT, Lako A, Eck MJ, Gray NS, Mitchison TJ, Cantley LC, Zhao JJ. Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival. Proc Natl Acad Sci U S A 2016; 113:9810-5. 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; 22:723-6. 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; 15:2692-704. PubMed
  • Goel S, Zhao JJ. CDK4/6 inhibition: the late harvest cycle begins. 2016. PubMed
  • Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, Tuck D, Harris LN, Wong KK, Liu XS, Sicinski P, Winer EP, Krop IE, Zhao JJ. Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors. Cancer Cell 2016; 29:255-69. 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. 2016. 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. PubMed
  • Wang Y, Zhang T, Kwiatkowski N, Abraham BJ, Lee TI, Xie S, Yuzugullu H, Von T, Li H, Lin Z, Stover DG, Lim E, Wang ZC, Iglehart JD, Young RA, Gray NS, Zhao JJ. CDK7-Dependent Transcriptional Addiction in Triple-Negative Breast Cancer. Cell 2015; 163:174-86. PubMed
  • 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
  • Yuzugullu H, Baitsch L, Von T, Steiner A, Tong H, Ni J, Clayton LK, Bronson R, Roberts TM, Gritsman K, Zhao JJ. A PI3K p110β-Rac signalling loop mediates Pten-loss-induced perturbation of haematopoiesis and leukaemogenesis. Nat Commun 2015; 6:8501. 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 p110α. J Clin Invest 2014; 124:1794-809. 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
  • 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 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 p110α and p110β 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 2010; 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
  • 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
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