MICHAEL THOMAS HEMANN. Curriculum Vitae. Koch Institute (617)

Transcription

1 MICHAEL THOMAS HEMANN Curriculum Vitae Koch Institute (617) MIT Department of Biology 77 Massachusetts Ave B Cambridge, MA Degrees: Ph.D., Human Genetics, Johns Hopkins University, 2001, Carol Greider B.A., Molecular Biology and Biochemistry, Wesleyan University, 1993 Employment: Postdoctoral Fellow, Cold Spring Harbor Laboratory, Scott Lowe Associate Professor of Biology, MIT, 2011-present Assistant Professor of Biology, MIT, External Positions Held: Honors: Associate Member, Broad Institute, 2006-present Mette Strand Young Investigator Award, Johns Hopkins, 2001 Harold M. Weintraub Graduate Student Award, 2001 Helen Hay Whitney Postdoctoral Fellowship, V Foundation Fellow, Rita Allen Foundation Scholar, Latham Family Career Development Chair in Biology, Eisen and Chang Career Development Chair in Biology, 2001-present UROP Students Supervised: Dubrovsky, Esther, Summer and Fall, 2006 Current position: Surgical Resident-Methodist Hospital, Houston, TX Ter-Ovanesyan, Dmitry, Spring-Summer-Fall 2007, IAP-Spring-Summer-Fall 2008, IAP 2009, Current position: Graduate Student, Harvard Medical School Ho, Em, Summer-Fall Current position: Graduate Student, Berkeley University Wu, Stephanie, IAP-Summer-Fall 2008, Spring-Summer 2009, IAP 2010 Current Position: Medical Student, NYU Medical School Hu, Marie, Spring-Summer-Fall 2010 Current Position: Undergraduate Student, MIT

2 Ph.D. Students Supervised: Doles, Jason, "Identification and Characterization of Modulators of Chemotherapeutic Response in Mouse Models of Cancer", 2010 Current position: Post-doctoral Fellow, B. Keyes laboratory, Centre for Genomic Regulation, Barcelona, Spain Meacham, Corbin, "In vivo pool-based shrna screens to identify modulators of disease progression in hematopoietic malignancies", 2011 Current position: Post-doctoral Associate, S. Morrison s Laboratory, University of Texas Southwestern, Dallas, TX Gilbert, Luke, "DNA damage mediated remodeling of normal and tumor microenvironments modulates cell survival", 2012 Current position: Post-doctoral Associate, J. Weissman s laboratory, UCSF Pritchard, Justin (co-advised by Doug Lauffenburger), Systems Level Characterizations of Single and Combination Drug Mechanisms of Action in vitro and in vivo, 2012 Current Position: Post-doctoral Associate, E. Rubin s laboratory, Harvard Ricks, Jennifer, in progress Cameron, Eleanor, in progress Bruno, Peter, in progress Soto-Feliciano, Yadira, in progress Zhao, Boyang (co-advised by Doug Lauffenburger), in progress Bent, Eric, in progress Postdoctoral Researchers Supervised: Jiang, Hai, Principle Investigator, Shanghai Institute of Biochemistry and Cell Biology Pallasch, Christian, Physician/Scientist, University Hospital of Cologne Braun, Christian, 2011-present Fenouille, Nina, 2011-present Teaching Experience: Service: 7.31 (Lectures), Advanced Topics in Mammalian Development, , Methods and Logic, Fall , Project Lab, Spring (Lectures), Cancer Biology, , Genetics, Spring 2013 Internal Service: Koch Institute Faculty Search Committee, Biology Undergraduate Committee, 2008-present

3 Organized Biology IAP, 2009 Whitehead Institute Faculty Search Committee, 2010 Faculty Supervisor, Applied Imaging Core Facility, Faculty Supervisor, Viral Production Core Facility, Faculty Surpervisor, Screening Core Facility, 2010-present Publications: Zhao B, Pritchard JR, Lauffenburger DA, Hemann MT. Addressing genetic tumor heterogeneity through computationally predictive combination therapy. Cancer Discov Feb;4(2): NIHMSID: *Pallasch C, Leskov I, Braun C, Vorholt D, Drake A, Soto-Feliciano Y, Bent E, Schwamb J, Iliopoulou B, Kutsch N, van Rooijen N, Frenzel L, Wendtner C, Heukamp L, Kreuzer K, Hallek M, Chen J, Hemann M. Sensitizing Protective Tumor Microenvironments to Antibody-Mediated Therapy. Cell Jan 30;156(3): NIHMSID: Suntharalingam K, Johnstone TC, Bruno PM, Lin W, Hemann MT, Lippard SJ. Bidentate ligands on osmium(vi) nitrido complexes control intracellular targeting and cell death pathways. J Am Chem Soc Sep 25;135(38): PMCID: PMC Wilson JL, Hemann MT, Fraenkel E, Lauffenburger DA. Integrated network analyses for functional genomic studies in cancer. Semin Cancer Biol Aug;23(4): PMCID: PMC *Pritchard JR, Bruno PM, Hemann MT, Lauffenburger DA. Predicting cancer drug mechanisms of action using molecular network signatures. Mol Biosyst Jul;9(7): NIHMSID: Braun CJ, Hemann MT. Unraveling tumor suppressor networks with in vivo RNAi. Cell Stem Cell Jun 6;12(6): Pavlova NN, Pallasch C, Elia AE, Braun CJ, Westbrook TF, Hemann M, Elledge SJ. A role for PVRL4-driven cell-cell interactions in tumorigenesis. Elife Apr 30;2:e PMCID: PMC Leskov I, Pallasch CP, Drake A, Iliopoulou BP, Souza A, Shen CH, Schweighofer CD, Abruzzo L, Frenzel LP, Wendtner CM, Hemann MT, Chen J. Rapid generation of human B-cell lymphomas via combined expression of Myc and Bcl2 and their use as a preclinical model for biological therapies. Oncogene Feb 21;32(8): NIHMSID: *Pritchard JR, Bruno PM, Gilbert LA, Capron KL, Lauffenburger DA, Hemann MT. Defining principles of combination drug mechanisms of action. Proc Natl Acad Sci U S A Jan 8;110(2):E PMCID: PMC *Pritchard JR, Lauffenburger DA, Hemann MT. Understanding resistance to combination chemotherapy. Drug Resist Updat Oct;15(5-6): NIHMSID:

4 *Gilbert LA, Hemann MT. Context-specific roles for paracrine IL-6 in lymphomagenesis. Genes Dev Aug 1;26(15): PMCID: PMC *Pritchard JR, Gilbert LA, Meacham CE, Ricks JL, Jiang H, Lauffenburger DA, Hemann MT. (2011). Bcl-2 family genetic profiling reveals microenvironmentspecific determinants of chemotherapeutic response. Cancer Res., 71(17), PMCID: PMC Gilbert LA, Hemann MT. (2011). Chemotherapeutic resistance: surviving stressful situations. Cancer Res., 71(15), PMCID: PMC Stadanlick JE, Zhang Z, Lee SY, Hemann M, Biery M, Carleton MO, Zambetti GP, Anderson SJ, Oravecz T, Wiest DL. (2011). Developmental arrest of T cells in Rpl22-deficient mice is dependent upon multiple p53 effectors. J Immunol., 187(2), PMCID: PMC *Jiang H, Pritchard JR, Williams RT, Lauffenburger DA, Hemann MT. (2011) A mammalian functional-genetic approach to characterizing cancer therapeutics. Nat. Chem. Biol., 7(2), PMCID: PMC *Xie K, Doles J, Hemann MT, Walker GC. (2010) Error-prone translesion synthesis mediates acquired chemoresistance. Proc. Natl. Acad. Sci. USA, 107(48), PMCID: PMC *Doles J, Oliver TG, Cameron ER, Hsu G, Jacks T, Walker GC, Hemann MT. (2010) Suppression of Rev3, the catalytic subunit of Pol{zeta}, sensitizes drugresistant lung tumors to chemotherapy. Proc. Natl. Acad. Sci. USA, 107(48), PMCID: PMC Feldser DM, Kostova KK, Winslow MM, Taylor SE, Cashman C, Whittaker CA, Sanchez-Rivera FJ, Resnick R, Bronson R, Hemann MT, Jacks T. (2010). Stagespecific sensitivity to p53 restoration during lung cancer progression. Nature., 468(7323), PMCID: PMC *Gilbert LA, Hemann MT. (2010) DNA damage-mediated induction of a chemoresistant niche. Cell, 143(3), PMCID: PMC *Doles J and Hemann MT. NEK4 status affects differential sensitivity to microtubule poisons. Cancer Res Feb 1;70(3): PMCID: PMC Bric A, Miething C, Bialucha CU, Scuoppo C, Zender L, Krasnitz A, Xuan Z, Zuber J, Wigler M, Hicks J, McCombie RW, Hemann MT, Hannon GJ, Powers S, Lowe SW. (2009) Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model. Cancer Cell. Oct 6;16(4): PMCID: PMC Reinhardt HC, Jiang H, Hemann MT, Yaffe MB. (2009). Exploiting synthetic lethal interactions for targeted cancer therapy. Cell Cycle., 8(19), PMCID: PMC

5 *Meacham CE, Ho E, Dubrovsky E, Gertler FB and Hemann MT. In Vivo RNAi screening identifies regulators of actin dynamics as key determinants of lymphoma progression. Nature Genetics, (2009) Oct;41(10): PMCID: PMC Jiang H, Reinhardt HC, Bartkova J, Tommiska J, Blomqvist C, Nevanlinna H, Bartek J, Yaffe MB and Hemann MT. The combined status of ATM and p53 link tumor development with therapeutic response. Genes & Development, (2009) Aug 15;23(16) PMCID: PMC *Pritchard JR, Cosgrove BD, Hemann MT, Griffith LG, Wands JR, Lauffenburger DA. (2009). Three-kinase inhibitor combination recreates multipathway effects of a geldanamycin analogue on hepatocellular carcinoma cell death. Mol Cancer Ther., 8(8), PMCID: PMC Burgess, D.J., Doles, J., Zender, L., Xue, W., Ma, B., McCombie, W.R., Hannon, G.J., Lowe, S.W., Hemann, M.T. (2008). Topoisomerase levels determine chemotherapy response in vitro and in vivo. Proc Natl Acad Sci, 105(26), PMCID: PMC Mayr, C., Hemann, M.T., Bartel, D. (2007). Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science, 315(5818), Hemann, M.T. and Narita, M. (2007). Oncogenes and senescence: breaking down in the fast lane. Genes Dev, 21(1), 1-5. Hemann, M.T. and Lowe, S.W. (2006). The p53-bcl-2 connection. Cell Death Differ, 13(8), He, L, Thomson, JM, Hemann, MT, Hernando-Monge, E, Mu, D, Goodson, S, Powers, S, Cordon-Cardo, C, Lowe, SW, Hannon, G, Hammond, S (2005). A microrna polycistron as a potential human oncogene. Nature, 435(7043), Dickins, R., Hemann, M.T., Zilfou, J., Simpson, D., Ibarra, I., Hannon, G., Lowe, S.W. (2005). Probing tumor phenotypes using stable and regulated synthetic microrna precursors. Nat Genet, 37(11), Hemann, M.T., Bric, A., Teruya-Feldstein, J., Herbst, A., Nilsson, J., Cordon- Cardo, C., Cleveland, J., Tansey, W., Lowe, S.W. (2005). Evasion of the p53 tumor surveillance network by tumor-derived MYC mutants. Nature, 436(7052), He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. (2005). A microrna polycistron as a potential human oncogene. Nature., 435(7043), Herbst A, Hemann MT, Tworkowski KA, Salghetti SE, Lowe SW, Tansey WP. (2005). A conserved element in Myc that negatively regulates its proapoptotic activity. EMBO Rep., 6(2),

6 Hernando E, Nahlé Z, Juan G, Diaz-Rodriguez E, Alaminos M, Hemann M, Michel L, Mittal V, Gerald W, Benezra R, Lowe SW, Cordon-Cardo C. (2004). Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature., 430(7001), Chiang YJ, Hemann MT, Hathcock KS, Tessarollo L, Feigenbaum L, Hahn WC, Hodes RJ. (2004). Expression of telomerase RNA template, but not telomerase reverse transcriptase, is limiting for telomere length maintenance in vivo. Mol Cell Biol., 24(16), Hemann, M.T., Zilfou, J., Zhao, Z., Burgess, D., Hannon, G., Lowe, S. (2004). Suppression of tumorigenesis by the p53 target PUMA. Proc Natl Acad Sci, 101(25), Rabinowicz PD, Palmer LE, May BP, Hemann MT, Lowe SW, McCombie WR, Martienssen RA. (2003). Genes and transposons are differentially methylated in plants, but not in mammals. Genome Res., 13(12), O'Hearn SF, Huang CE, Hemann M, Zhelonkina A, Sollner-Webb B. (2003). Trypanosoma brucei RNA editing complex: band II is structurally critical and maintains band V ligase, which is nonessential. Mol Cell Biol., 23(21), Fridman JS, Hernando E, Hemann MT, de Stanchina E, Cordon-Cardo C, Lowe SW. (2003). Tumor promotion by Mdm2 splice variants unable to bind p53. Cancer Res., 63(18), Hemann, MT, Fridman, J, Zilfou, J, Hernando, E, Paddison, P, Cordon-Cardo, C, Hannon, G, Lowe, S (2003). An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo. Nat Genet, 33(3), Hemann, MT, Hathcock, K, Opperman, K, Strong, M, Greider, C, Hodes, R (2002). Haploinsufficiency of mtr results in defects in telomere elongation. Proc Natl Acad Sci, 99(6), Hemann MT, Strong MA, Hao LY, Greider CW. (2001). The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell., 107(1), Hemann, MT, Rudolph, K, Strong, M, DePinho, R, Chin, L, Greider, C (2001). Telomere dysfunction triggers developmentally regulated germ cell apoptosis. Mol Biol of the Cell, 12, Rusché LN, Huang CE, Piller KJ, Hemann M, Wirtz E, Sollner-Webb B. (2001). The two RNA ligases of the Trypanosoma brucei RNA editing complex: cloning the essential band IV gene and identifying the band V gene. Mol Cell Biol., 21(4), Hemann MT, Greider CW. (2000). Wild-derived inbred mouse strains have short telomeres. Nucleic Acids Res., 28(22),

7 Hemann MT, Hackett J, IJpma A, Greider CW. (2000). Telomere length, telomere-binding proteins, and DNA damage signaling. Cold Spring Harb Symp Quant Biol., 65, Hemann MT, Greider CW. (1999). G-strand overhangs on telomeres in telomerase-deficient mouse cells. Nucleic Acids Res., 27(20), Wagstaff J, Hemann M. (1995). A familial "balanced" 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings. Am J Hum Genet., 56(1), * - papers arising from a supervised thesis Invited Presentations: Using mouse models to identify cancer drug targets", Organon Research, Boston, Massachusetts, 2007 "Using mouse models to improve cancer therapy", Children s Memorial Research Center, Northwestern University, 2008 Performing RNAi screens in mouse models of cancer, Keystone Symposium on RNAi, MicroRNA, and Non-Coding RNA, Whistler, Canada, 2008 Mouse in vivo screening for mediators of chemotherapeutic response AACR, AACR Annual Meeting, San Diego, California, 2008 Finding a safe neighborhood: how lymphomas identify and migrate to chemoprotective microenvironments, Department of Neuro-Oncology, MGH, Boston, Massachusetts, 2008 The development of tractable mouse models to study therapeutic response, AACR International Conference on Frontiers in Cancer Prevention Research, Washington, DC, 2008 Engineering Mouse Models to Study Cancer Therapeutics, NYU Department of Pathology, New York, New York, 2008 In vivo screening to identify cancer drug targets, Mechanisms & Models of Cancer Meeting, Cold Spring Harbor Laboratory, New York, 2008 Performing RNAi screens in mouse models of cancer, AACR Annual Meeting, Denver, Colorado, 2009 Using mouse models to identify cancer drug targets", Schering Plough Research Institute, Boston, Massachusetts, 2009

8 The development of tractable mouse models to study therapeutic response, Department of Oncological Sciences & Dermatology, Mount Sinai School of Medicine, New York, New York, 2009 The development of tractable mouse models to study therapeutic response, Mechanisms & Models of Cancer Meeting, Salk Institute, La Jolla, California, 2009 Performing RNAi screens in mouse models of cancer, Genetic Screening in Mouse Cancer Models Meeting, Wellcome Trust Conference Centre, Hinxton, Cambridge, UK, 2009 "Identifying cancer drug targets using in vivo RNAi", Constellation Pharmaceuticals, Cambridge, Massachusetts, 2010 Using RNAi signatures to identify drug tagets and improve cancer therapy MIT- Merck Symposium, Boston, Massachusetts, 2010 Performing loss of function screens in mice, Genetics Society's Model Organisms Meeting, Boston, Massachusetts, 2010 Importance of p53 and ATM status in predicting therapeutic response to targeted therapies, EuroCancer 2010, Paris, France, 2010 "Performing genetic screens in mouse models of cancer", Immunology and Pathogenesis seminar series, Berkeley, 2010 "Performing genetic screens in mouse models of cancer", UCSF Comprehensive Cancer Center, 2010 "Using mouse models to improve cancer therapy", Microbiology Seminar Series, University of Virginia, 2010 Autocrine and paracrine signaling during metastatic progression, Koch Institute- Janssen Pharmaceutica Scienific Exchange, Beerse, Belgium, 2011 A Role for the DNA damage response in tumor cell survival and acquired chemoresistance Keystone Symposia, Keystone, Colorado, 2011 "Therapy-induced survival signaling in the tumor microenvironment" NCI-TMEN Winter Meeting Workshop, Bethesda, MD, 2011 Using RNAi signatures to investigate drug action and resistance mechanisms AACR-NCI Conference on Systems Biology, San Diego, CA, 2011 Using old mouse models to identify new cancer drug targets, AACR Annual

9 Meeting, Orlando, FL, 2011 Using mouse models to improve cancer therapy, University of Massachusetts Medical School, Worcester, MA, 2011 Cancer gene discovery through in vivo RNAi screens, Mechanisms & Models of Cancer Meeting, Salk Institute, La Jolla, California, 2011 Developing tractable mouse models to study and improve cancer therapy, NIBR Emeryville Building Bridges Seminar Series, Novartis Institutes for Biomedical Research, Emeryville, CA, 2011 Screening the tumor microenvironment for new drug targets, AACR International Conference on Frontiers in Basic Cancer Research, San Francisco, CA, 2011 Assessing the role of the tumor micro- environment in chemotherapeutic response, Ulm University Fall Meeting, Ulm, Germany, 2011 Modeling the role of the tumor microenvironment in therapeutic response, NCRI Cancer Conference, Liverpool, UK, 2011 Using mouse models to improve cancer therapy, Labwide Seminar Series, Cold Spring Harbor Laboratory, New York, 2011 "Using Mouse Models to Improve Cancer Therapy", Seminars In Oncology, Dana Farber Cancer Institute, Boston, MA 2011 Using mouse models to improve cancer therapy, Cancer Biology Seminar Series, University of Chicago, Chicago, IL, 2012 Investigating the role of the tumor microenvironment in chemotherapeutic response, Lorne Cancer Conference, Lorne, Australia, 2012 "Using mouse models to improve cancer therapy", WEHI special seminar, Melbourne, Australia, 2012 Strategies for pool based RNAi screening, Molecular and Cellular Basis of Disease Symposium, Case Western Reserve University, Cleveland, OH, 2012 "Screening the tumor microenvironment for new drug targets", AACR Annual Meeting, Chicago, IL, 2012 Modeling the role of the tumor microenvironment in chemotherapeutic response The Cancer Genome and Proteome Seminar Series, Netherlands Cancer Institute, Amsterdam, Netherlands, 2012

10 Finding more targets within the tumor cell using a functional-genetic approach, International Symposium of the Collaborative Research Center 832, Bad Neuenahr Ahrweiler, Germany, 2012 Using mouse models to identify new cancer drug targets, CeMMinar Series, Research Center for Molecular Medicine, Vienna, Austria, 2012 Using mouse models to identify cancer drug targets, Cancer Therapeutics Symposium, Huntsman Cancer Institute, Salt Lake City, UT, 2012 Using Mouse Models to Improve Cancer Therapy Targeting the Tumor Microenvironment, Boston, MA, 2012 "Using Mouse Models to Improve Cancer Therapy", Biomolecular Seminar Series, Boston University, Boston, MA 2012 Research Contracts and Grants: Helen Hay Whitney Post-Doctoral Fellowship 01/01/ /31/2005, $120,000 V Foundation Fellowship, Identifying Determinants of Chemotherape Response, 11/01/ /31/2008, $60,606 Latham Family Assistant Professorship, 06/01/ /09/2011, $60,000 Rita Allen Foundation Fellowship, Performing high-throughput in vivo pool-based RNAi screens, 07/01/ /30/2010, $249,957 NIH 5-R01-CA128803, Identifying determinants of chemotherapeutic response in vivo, 09/26/ /31/2013, $840,315 KI Developmental Funds, Identifying regulators of lymphoma CNS dissemination, 05/01/ /30/2009, $31,110 Schering Plough Research Institute, Discovery and validation of cancer targets for antibody-mediated chemosensitization, 12/01/ /30/2011, $109,281 Ludwig Fund for Cancer Research, Understanding the mechanisms responsible for cancer cell invasiveness (Weinberg, PI), 09/01/2009-8/31/2013, $125,000/year (Hemann Lab) NIH U54-CA112967, ICBP Tumor Cell Networks Center (Lauffenburger, PI), 03/01/ /28/2015, $450,000 (Hemann Lab)

11 Marble Foundation Funding, Metastasis and Therapeutic Response of B Cell Leukemia/Lymphoma in Humanized Mice, 03/01/2010-indefinite, $123,182 Ortho-McNeil-Janssen, TRANSCEND: Regulation of cytokine signaling by the tumor microenvironment (Yaffe, PI), 01/01/ /31/2013, $202,743 (Hemann Lab) Ortho-McNeil-Janssen, TRANSCEND: Tumor cell microenvironment interactions during intravasation (Gertler, PI), 03/15/ /31/2013, $91,033 (Hemann Lab) MIT Biology Eisen/Chang Chair, 07/01/2011-indefinite, $20,000 Johns Hopkins University (NIH) 1-UO1CA155758, Analysis of the signaling and mechanical cues promoting metastasis in melanoma (Levchenko, PI), 09/01/ /31/2016, $69,412/year (Hemann Lab) Contributions to the Educational Commons: Reading graduate school admissions folders, Presenting at UROP orientation, Biology class dinners and Applying to Graduate School annual dinners, 2008-present Organizing Koch Institute Annual Retreats, Hosting MSRP summer research fellows, Academic advisor to 13 undergraduates Serve(d) on approximately 35 thesis committees