Photo of Aaron Hata,  MD, PhD

Aaron Hata, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-3442


ahata@mgh.harvard.edu

Aaron Hata, MD, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Assistant Physician, Medicine, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The research goal of the Hata laboratory is to advance targeted therapies to benefit patients with lung cancer. Our research focuses on understanding the biological underpinnings of sensitivity and resistance to kinase inhibitor targeted therapies in lung cancers with specific genetic abnormalities (EGFR mutations, ALK translocations, KRAS mutations). In particular, we seek to understand how kinase inhibitors modulate signaling networks that regulate cancer cell growth and survival, and characterize the molecular mechanisms of acquired resistance to these agents. More recently, we have begun to focus on understanding how cancer cells adapt and evolve during the course of therapy in order to identify vulnerabilities of drug tolerant cancer cells that might be exploited to prevent resistance from developing. Our studies are highly translational, combining cell culture models, patient-derived mouse (PDX) models and assessment of clinical specimens, and are performed in close collaboration with clinicians in the Thoracic Oncology group.

Publications from Harvard Catalyst Profiles

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  • Hu H, Piotrowska Z, Hare PJ, Chen H, Mulvey HE, Mayfield A, Noeen S, Kattermann K, Greenberg M, Williams A, Riley AK, Wilson JJ, Mao YQ, Huang RP, Banwait MK, Ho J, Crowther GS, Hariri LP, Heist RS, Kodack DP, Pinello L, Shaw AT, Mino-Kenudson M, Hata AN, Sequist LV, Benes CH, Niederst MJ, Engelman JA. Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms. Cancer Cell 2021; 39:1531-1547.e10. PubMed
  • Oren Y, Tsabar M, Cuoco MS, Amir-Zilberstein L, Cabanos HF, Hütter JC, Hu B, Thakore PI, Tabaka M, Fulco CP, Colgan W, Cuevas BM, Hurvitz SA, Slamon DJ, Deik A, Pierce KA, Clish C, Hata AN, Zaganjor E, Lahav G, Politi K, Brugge JS, Regev A. Cycling cancer persister cells arise from lineages with distinct programs. Nature 2021. PubMed
  • Tsai JM, Hata AN, Lennerz JK. MET D1228N and D1246N are the Same Resistance Mutation in MET Exon 14 Skipping. Oncologist 2021. PubMed
  • Willers H, Pan X, Borgeaud N, Korovina I, Koi L, Egan R, Greninger P, Rosenkranz A, Kung J, Liss AS, Parsels LA, Morgan MA, Lawrence TS, Lin SH, Hong TS, Yeap BY, Wirth L, Hata AN, Ott CJ, Benes CH, Baumann M, Krause M. Screening and Validation of Molecular Targeted Radiosensitizers. Int J Radiat Oncol Biol Phys 2021. PubMed
  • Davoudi F, Ghorbanpoor S, Yoda S, Pan X, Crowther GS, Yin X, Murchie E, Hata AN, Willers H, Benes CH. Alginate-based 3D cancer cell culture for therapeutic response modeling. STAR Protoc 2021; 2:100391. PubMed
  • Cabanos HF, Hata AN. Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer. Cancers (Basel) 2021. PubMed
  • Al Zubaidi T, Gehrisch OHF, Genois MM, Liu Q, Lu S, Kung J, Xie Y, Schuemann J, Lu HM, Hata AN, Zou L, Borgmann K, Willers H. Targeting the DNA replication stress phenotype of KRAS mutant cancer cells. Sci Rep 2021; 11:3656. PubMed
  • Dagogo-Jack I, Moonsamy P, Gainor JF, Lennerz JK, Piotrowska Z, Lin JJ, Lennes IT, Sequist LV, Shaw AT, Goodwin K, Stevens SE, Do A, Digumarthy SR, Price K, Muzikansky A, Hata AN, Heist RS. A Phase II Study of Capmatinib in Patients with MET-Altered Lung Cancer Previously Treated with a MET Inhibitor. J Thorac Oncol 2021. PubMed
  • Poels KE, Schoenfeld AJ, Makhnin A, Tobi Y, Wang Y, Frisco-Cabanos H, Chakrabarti S, Shi M, Napoli C, McDonald TO, Tan W, Hata A, Weinrich SL, Yu HA, Michor F. Identification of optimal dosing schedules of dacomitinib and osimertinib for a phase I/II trial in advanced EGFR-mutant non-small cell lung cancer. Nat Commun 2021; 12:3697. PubMed
  • Slyper M, Porter CBM, Ashenberg O, Waldman J, Drokhlyansky E, Wakiro I, Smillie C, Smith-Rosario G, Wu J, Dionne D, Vigneau S, Jané-Valbuena J, Tickle TL, Napolitano S, Su MJ, Patel AG, Karlstrom A, Gritsch S, Nomura M, Waghray A, Gohil SH, Tsankov AM, Jerby-Arnon L, Cohen O, Klughammer J, Rosen Y, Gould J, Nguyen L, Hofree M, Tramontozzi PJ, Li B, Wu CJ, Izar B, Haq R, Hodi FS, Yoon CH, Hata AN, Baker SJ, Suvà ML, Bueno R, Stover EH, Clay MR, Dyer MA, Collins NB, Matulonis UA, Wagle N, Johnson BE, Rotem A, Rozenblatt-Rosen O, Regev A. A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors. Nat Med 2020; 26:792-802. PubMed
  • Piotrowska Z, Hata AN. Resistance to First-Line Osimertinib in EGFR-mutant NSCLC: Tissue is the Issue. Clin Cancer Res 2020. PubMed
  • Meador CB, Hata AN. Acquired resistance to targeted therapies in NSCLC: Updates and evolving insights. Pharmacol Ther 2020. PubMed
  • Dagogo-Jack I, Yoda S, Lennerz JK, Langenbucher A, Lin JJ, Rooney MM, Prutisto-Chang K, Oh A, Adams NA, Yeap BY, Chin E, Do A, Marble HD, Stevens SE, Digumarthy SR, Saxena A, Nagy RJ, Benes CH, Azzoli CG, Lawrence MS, Gainor JF, Shaw AT, Hata AN. MET Alterations are a Recurring and Actionable Resistance Mechanism in ALK-Positive Lung Cancer. Clin Cancer Res 2020. PubMed
  • Millar DG, Ramjiawan RR, Kawaguchi K, Gupta N, Chen J, Zhang S, Nojiri T, Ho WW, Aoki S, Jung K, Chen I, Shi F, Heather JM, Shigeta K, Morton LT, Sepulveda S, Wan L, Joseph R, Minogue E, Khatri A, Bardia A, Ellisen LW, Corcoran RB, Hata AN, Pai SI, Jain RK, Fukumura D, Duda DG, Cobbold M. Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy. Nat Biotechnol 2020. PubMed
  • Klempner SJ, Hata AN. Can the Help Match the Hype? KRAS-Specific Inhibitors and Beyond. 2020; 10:20-22. PubMed
  • Hata AN, Shaw AT. Resistance looms for KRAS inhibitors. Nat Med 2020; 26:169-170. PubMed
  • Klempner SJ, Hata AN. Sequence, Treat, Repeat: Addressing Resistance in EGFR-Mutant NSCLC. J Thorac Oncol 2019; 14:1875-1877. PubMed
  • Dagogo-Jack I, Piotrowska Z, Cobb R, Banwait M, Lennerz JK, Hata AN, Digumarthy SR, Sequist LV. Response to the Combination of Osimertinib and Trametinib in a Patient With EGFR-Mutant NSCLC Harboring an Acquired BRAF Fusion. J Thorac Oncol 2019; 14:e226-e228. PubMed
  • Farago AF, Yeap BY, Stanzione M, Hung YP, Heist RS, Marcoux JP, Zhong J, Rangachari D, Barbie DA, Phat S, Myers DT, Morris R, Kem M, Dubash TD, Kennedy EA, Digumarthy SR, Sequist LV, Hata AN, Maheswaran S, Haber DA, Lawrence MS, Shaw AT, Mino-Kenudson M, Dyson NJ, Drapkin BJ. Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer. 2019; 9:1372-1387. PubMed
  • Niu J, Sun Y, Chen B, Zheng B, Jarugumilli GK, Walker SR, Hata AN, Mino-Kenudson M, Frank DA, Wu X. Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation. Nature 2019; 573:139-143. PubMed
  • Raoof S, Mulford IJ, Frisco-Cabanos H, Nangia V, Timonina D, Labrot E, Hafeez N, Bilton SJ, Drier Y, Ji F, Greenberg M, Williams A, Kattermann K, Damon L, Sovath S, Rakiec DP, Korn JM, Ruddy DA, Benes CH, Hammerman PS, Piotrowska Z, Sequist LV, Niederst MJ, Barretina J, Engelman JA, Hata AN. Targeting FGFR overcomes EMT-mediated resistance in EGFR mutant non-small cell lung cancer. Oncogene 2019; 38:6399-6413. PubMed
  • Katayama R, Gong B, Togashi N, Miyamoto M, Kiga M, Iwasaki S, Kamai Y, Tominaga Y, Takeda Y, Kagoshima Y, Shimizu Y, Seto Y, Oh-Hara T, Koike S, Nakao N, Hanzawa H, Watanabe K, Yoda S, Yanagitani N, Hata AN, Shaw AT, Nishio M, Fujita N, Isoyama T. The new-generation selective ROS1/NTRK inhibitor DS-6051b overcomes crizotinib resistant ROS1-G2032R mutation in preclinical models. Nat Commun 2019; 10:3604. PubMed
  • Dagogo-Jack I, Rooney MM, Lin JJ, Nagy RJ, Yeap BY, Hubbeling H, Chin E, Ackil J, Farago AF, Hata AN, Lennerz JK, Gainor JF, Lanman RB, Shaw AT. Treatment with Next-Generation ALK Inhibitors Fuels Plasma ALK Mutation Diversity. Clin Cancer Res 2019. PubMed
  • Marcar L, Bardhan K, Gheorghiu L, Dinkelborg P, Pfäffle H, Liu Q, Wang M, Piotrowska Z, Sequist LV, Borgmann K, Settleman JE, Engelman JA, Hata AN, Willers H. Acquired Resistance of EGFR-Mutated Lung Cancer to Tyrosine Kinase Inhibitor Treatment Promotes PARP Inhibitor Sensitivity. Cell Rep 2019; 27:3422-3432.e4. PubMed
  • Grassberger C, McClatchy DM, Geng C, Kamran SC, Fintelmann F, Maruvka YE, Piotrowska Z, Willers H, Sequist LV, Hata AN, Paganetti H. Patient-specific tumor growth trajectories determine persistent and resistant cancer cell populations during treatment with targeted therapies. Cancer Res 2019. PubMed
  • Misale S, Fatherree JP, Cortez E, Li C, Bilton S, Timonina D, Myers DT, Lee D, Gomez-Caraballo M, Greenberg M, Nangia V, Greninger P, Egan RK, McClanaghan J, Stein GT, Murchie E, Zarrinkar PP, Janes MR, Li LS, Liu Y, Hata AN, Benes CH. KRAS G12C NSCLC Models Are Sensitive to Direct Targeting of KRAS in Combination with PI3K Inhibition. Clin Cancer Res 2018. PubMed
  • Nangia V, Siddiqui FM, Caenepeel S, Timonina D, Bilton SJ, Phan N, Gomez-Caraballo M, Archibald HL, Li C, Fraser C, Rigas D, Vajda K, Ferris LA, Lanuti M, Wright CD, Raskin KA, Cahill DP, Shin JH, Keyes C, Sequist LV, Piotrowska Z, Farago AF, Azzoli CG, Gainor JF, Sarosiek KA, Brown SP, Coxon A, Benes CH, Hughes PE, Hata AN. Exploiting MCL-1 dependency with combination MEK + MCL-1 inhibitors leads to induction of apoptosis and tumor regression in KRAS mutant non-small cell lung cancer. 2018. PubMed
  • Yoda S, Dagogo-Jack I, Hata AN. Targeting oncogenic drivers in lung cancer: Recent progress, current challenges and future opportunities. Pharmacol Ther 2018. PubMed
  • Song KA, Hosono Y, Turner C, Jacob S, Lochmann TL, Murakami Y, Patel NU, Ham J, Hu B, Powell KM, Coon CM, Windle BE, Oya Y, Koblinski JE, Harada H, Leverson JD, Souers AJ, Hata AN, Boikos S, Yatabe Y, Ebi H, Faber AC. Increased Synthesis of MCL-1 Protein Underlies Initial Survival of -Mutant Lung Cancer to EGFR Inhibitors and Provides a Novel Drug Target. Clin Cancer Res 2018. PubMed
  • Drapkin BJ, George J, Christensen CL, Mino-Kenudson M, Dries R, Sundaresan T, Phat S, Myers DT, Zhong J, Igo P, Hazar-Rethinam MH, LiCausi JA, Gomez-Caraballo M, Kem M, Jani KN, Azimi R, Abedpour N, Menon R, Lakis S, Heist RS, Büttner R, Haas S, Sequist LV, Shaw AT, Wong KK, Hata AN, Toner M, Maheswaran S, Haber DA, Peifer M, Dyson N, Thomas RK, Farago AF. Genomic and functional fidelity of small cell lung cancer patient-derived xenografts. 2018. PubMed
  • Lin JJ, Zhu VW, Yoda S, Yeap BY, Schrock AB, Dagogo-Jack I, Jessop NA, Jiang GY, Le LP, Gowen K, Stephens PJ, Ross JS, Ali SM, Miller VA, Johnson ML, Lovly CM, Hata AN, Gainor JF, Iafrate AJ, Shaw AT, Ou SI. Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer. J Clin Oncol 2018. PubMed
  • Piotrowska Z, Hazar-Rethinam M, Rizzo C, Nadres B, Van Seventer EE, Shahzade HA, Lennes IT, Iafrate AJ, Dias-Santagata D, Leshchiner I, Jessop NA, Hu H, Digumarthy SR, Nagy RJ, Lanman RB, Moody S, Niederst MJ, Engelman JA, Hata AN, Corcoran RB, Sequist LV. Heterogeneity and Coexistence of T790M and T790 Wild-Type Resistant Subclones Drive Mixed Response to Third-Generation Epidermal Growth Factor Receptor Inhibitors in Lung Cancer. JCO Precis Oncol 2018. PubMed
  • Song KA, Niederst MJ, Lochmann TL, Hata AN, Kitai H, Ham J, Floros KV, Hicks MA, Hu H, Mulvey HE, Drier Y, Heisey DAR, Hughes MT, Patel NU, Lockerman EL, Garcia A, Gillepsie S, Archibald HL, Gomez-Caraballo M, Nulton TJ, Windle BE, Piotrowska Z, Sahingur SE, Taylor SM, Dozmorov M, Sequist LV, Bernstein B, Ebi H, Engelman JA, Faber AC. Epithelial-to-Mesenchymal Transition Antagonizes Response to Targeted Therapies in Lung Cancer by Suppressing BIM. Clin Cancer Res 2018; 24:197-208. PubMed
  • Dagogo-Jack I, Brannon AR, Ferris LA, Campbell CD, Lin JJ, Schultz KR, Ackil J, Stevens S, Dardaei L, Yoda S, Hubbeling H, Digumarthy SR, Riester M, Hata AN, Sequist LV, Lennes IT, Iafrate AJ, Heist RS, Azzoli CG, Farago AF, Engelman JA, Lennerz JK, Benes CH, Leary RJ, Shaw AT, Gainor JF. Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors through Longitudinal Analysis of Circulating Tumor DNA. JCO Precis Oncol 2018. PubMed
  • Gainor JF, Tseng D, Yoda S, Dagogo-Jack I, Friboulet L, Lin JJ, Hubbeling HG, Dardaei L, Farago AF, Schultz KR, Ferris LA, Piotrowska Z, Hardwick J, Huang D, Mino-Kenudson M, Iafrate AJ, Hata AN, Yeap BY, Shaw AT. Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in-Positive Non-Small-Cell Lung Cancer. JCO Precis Oncol 2017. PubMed
  • Mooradian MJ, Piotrowska Z, Drapkin BJ, Dias-Santagata D, Marcoux N, Arnaoutakis K, Nagy RJ, Lanman R, Iafrate AJ, Farago AF, Mino-Kenudson M, Hata AN, Sequist LV. Clonal Evolution and the Role of Serial Liquid Biopsies in a Case of Small-Cell Lung Cancer-Transformed Mutant Non-Small-Cell Lung Cancer. JCO Precis Oncol 2017. PubMed
  • Hata AN, Niederst MJ, Archibald HL, Gomez-Caraballo M, Siddiqui FM, Mulvey HE, Maruvka YE, Ji F, Bhang HE, Krishnamurthy Radhakrishna V, Siravegna G, Hu H, Raoof S, Lockerman E, Kalsy A, Lee D, Keating CL, Ruddy DA, Damon LJ, Crystal AS, Costa C, Piotrowska Z, Bardelli A, Iafrate AJ, Sadreyev RI, Stegmeier F, Getz G, Sequist LV, Faber AC, Engelman JA. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat Med 2016; 22:262-9. PubMed
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