Investigator, Hale Family Center For Pancreatic Cancer Research
Chief Scientific Officer
Interim Executive Vice President & Chief Operating Officer
Department Of Medical Oncology, Dana-Farber Cancer Institute
William Rosenberg Professor Of Medicine, Harvard Medical School
Institute Member, Broad Institute
Bio Research Interests Key Publications Hahn Lab Website
Bio
Dr. William Hahn, MD, PhD has made numerous seminal discoveries that have informed our current molecular understanding of cancer and which have defined new conceptual paradigms and formed the foundation of new translational studies. His laboratory has helped develop widely adopted experimental models and genome scale tools and technology to perform somatic cell genetics in human cells.
His laboratory has pioneered the use of integrated functional genomic approaches to identify and validate cancer targets. The tools, models, and approaches that his laboratory has developed have already become widely used worldwide to discover and validate molecularly targeted cancer therapies. Dr. Hahn and his collaborators are now engaged in clinical trials testing whether inhibition of either newly-identified oncogenic targets or synthetic lethal partners will lead to clinical responses.
Dr. Hahn has served as the President of the American Society For Clinical Investigation and has been the recipient of many honors and awards, including the Wilson S. Stone Award from M.D. Anderson Cancer Center (2000), the Ho-Am Prize In Medicine (2010), and the AACR Richard And Hinda Rosenthal Memorial Award (2015).
Research Interests
The Hahn Lab focuses on understanding the cooperative interactions that conspire to transform human cells. To address this question, we have developed new experimental models of human cancer of defined genetic composition; created tools and methods to perform genome scale, systematic interrogation of gene function in mammalian cells and tissues (RNAi, CRISPR, ORFs); and developed new approaches to integrate genome scale data.
Using these approaches, we have identified and credentialed new oncogenes and tumor suppressor genes, and have performed preclinical studies that will form the foundation necessary for translational studies in patients.
Over the past several years, we have focused on understanding the KRAS oncogene in pancreas and other cancers. Using integrated genomic approaches together with our colleagues in the Hale Family Center For Pancreatic Cancer Research, we have identified several genes whose activity is necessary for the survival of KRAS-driven cancers and are developing approaches to therapeutically target these co-dependencies.
Key Publications
Giacomelli AO, Yang X, Lintner RE, McFarland JM, Duby M, Kim J, Howard TP, Takeda DY, Ly SH, Kim E, Gannon HS, Hurhula B, Sharpe T, Goodale A, Fritchman B, Steelman S, Vazquez F, Tsherniak A, Aguirre AJ, Doench JG, Piccioni F, Roberts CWM, Meyerson M, Getz G, Johannessen CM, Root DE, Hahn WC. Mutational processes shape the landscape of TP53 mutations in human cancer. Nat Genet. 2018;50(10):1381-7. Epub 2018/09/19. doi: 10.1038/s41588-018-0204-y. PubMed PMID: 30224644; PMCID: PMC6168352.
Aguirre AJ, Nowak JA, Camarda ND, Moffitt RA, Ghazani AA, Hazar-Rethinam M, Raghavan S, Kim J, Brais LK, Ragon D, Welch MW, Reilly E, McCabe D, Marini L, Anderka K, Helvie K, Oliver N, Babic A, Da Silva A, Nadres B, Van Seventer EE, Shahzade HA, St Pierre JP, Burke KP, Clancy T, Cleary JM, Doyle LA, Jajoo K, McCleary NJ, Meyerhardt JA, Murphy JE, Ng K, Patel AK, Perez K, Rosenthal MH, Rubinson DA, Ryou M, Shapiro GI, Sicinska E, Silverman SG, Nagy RJ, Lanman RB, Knoerzer D, Welsch DJ, Yurgelun MB, Fuchs CS, Garraway LA, Getz G, Hornick JL, Johnson BE, Kulke MH, Mayer RJ, Miller JW, Shyn PB, Tuveson DA, Wagle N, Yeh JJ, Hahn WC, Corcoran RB, Carter SL, Wolpin BM. Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine. Cancer Discov. 2018;8(9):1096-111. Epub 2018/06/16. doi: 10.1158/2159-8290.CD-18-0275. PubMed PMID: 29903880.
Yurgelun MB, Chittenden AB, Morales-Oyarvide V, Rubinson DA, Dunne RF, Kozak MM, Qian ZR, Welch MW, Brais LK, Da Silva A, Bui JL, Yuan C, Li T, Li W, Masuda A, Gu M, Bullock AJ, Chang DT, Clancy TE, Linehan DC, Findeis-Hosey JJ, Doyle LA, Thorner AR, Ducar MD, Wollison BM, Khalaf N, Perez K, Syngal S, Aguirre AJ, Hahn WC, Meyerson ML, Fuchs CS, Ogino S, Hornick JL, Hezel AF, Koong AC, Nowak JA, Wolpin BM. Germline cancer susceptibility gene variants, somatic second hits, and survival outcomes in patients with resected pancreatic cancer. Genet Med. 2018. Epub 2018/07/03. doi: 10.1038/s41436-018-0009-5. PubMed PMID: 29961768.
Wang B, Krall EB, Aguirre AJ, Kim M, Widlund HR, Doshi MB, Sicinska E, Sulahian R, Goodale A, Cowley GS, Piccioni F, Doench JG, Root DE, Hahn WC. ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition. Cell Rep. 2017;18(6):1543-57. doi: 10.1016/j.celrep.2017.01.031. PubMed PMID: 28178529; PMCID: PMC5313047.
Tsherniak A, Vazquez F, Montgomery PG, Weir BA, Kryukov G, Cowley GS, Gill S, Harrington WF, Pantel S, Krill-Burger JM, Meyers RM, Ali L, Goodale A, Lee Y, Jiang G, Hsiao J, Gerath WFJ, Howell S, Merkel E, Ghandi M, Garraway LA, Root DE, Golub TR, Boehm JS, Hahn WC. Defining a Cancer Dependency Map. Cell. 2017;170(3):564-76 e16. doi: 10.1016/j.cell.2017.06.010. PubMed PMID: 28753430; PMCID: PMC5667678.
Qian ZR, Rubinson DA, Nowak JA, Morales-Oyarvide V, Dunne RF, Kozak MM, Welch MW, Brais LK, Da Silva A, Li T, Li W, Masuda A, Yang J, Shi Y, Gu M, Masugi Y, Bui J, Zellers CL, Yuan C, Babic A, Khalaf N, Aguirre A, Ng K, Miksad RA, Bullock AJ, Chang DT, Tseng JF, Clancy TE, Linehan DC, Findeis-Hosey JJ, Doyle LA, Thorner AR, Ducar M, Wollison B, Laing A, Hahn WC, Meyerson M, Fuchs CS, Ogino S, Hornick JL, Hezel AF, Koong AC, Wolpin BM. Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma. JAMA Oncol. 2017. doi: 10.1001/jamaoncol.2017.3420. PubMed PMID: 29098284.
Krall EB, Wang B, Munoz DM, Ilic N, Raghavan S, Niederst MJ, Yu K, Ruddy DA, Aguirre AJ, Kim JW, Redig AJ, Gainor JF, Williams JA, Asara JM, Doench JG, Janne PA, Shaw AT, McDonald Iii RE, Engelman JA, Stegmeier F, Schlabach MR, Hahn WC. KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer. Elife. 2017;6. doi: 10.7554/eLife.18970. PubMed PMID: 28145866; PMCID: PMC5305212.
Kim JW, Abudayyeh OO, Yeerna H, Yeang CH, Stewart M, Jenkins RW, Kitajima S, Konieczkowski DJ, Medetgul-Ernar K, Cavazos T, Mah C, Ting S, Van Allen EM, Cohen O, McDermott J, Damato E, Aguirre AJ, Liang J, Liberzon A, Alexe G, Doench J, Ghandi M, Vazquez F, Weir BA, Tsherniak A, Subramanian A, Meneses-Cime K, Park J, Clemons P, Garraway LA, Thomas D, Boehm JS, Barbie DA, Hahn WC, Mesirov JP, Tamayo P. Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States. Cell Syst. 2017;5(2):105-18 e9. doi: 10.1016/j.cels.2017.08.002. PubMed PMID: 28837809; PMCID: PMC5639711.
Ilic N, Birsoy K, Aguirre AJ, Kory N, Pacold ME, Singh S, Moody SE, DeAngelo JD, Spardy NA, Freinkman E, Weir BA, Tsherniak A, Cowley GS, Root DE, Asara JM, Vazquez F, Widlund HR, Sabatini DM, Hahn WC. PIK3CA mutant tumors depend on oxoglutarate dehydrogenase. Proc Natl Acad Sci U S A. 2017;114(17):E3434-E43. doi: 10.1073/pnas.1617922114. PubMed PMID: 28396387; PMCID: PMC5410781.
Aguirre AJ, Hahn WC. Synthetic Lethal Vulnerabilities in KRAS-Mutant Cancers. Cold Spring Harb Perspect Med. 2017. doi: 10.1101/cshperspect.a031518. PubMed PMID: 29101114.
Kim JW, Botvinnik OB, Abudayyeh O, Birger C, Rosenbluh J, Shrestha Y, Abazeed ME, Hammerman PS, DiCara D, Konieczkowski DJ, Johannessen CM, Liberzon A, Alizad-Rahvar AR, Alexe G, Aguirre A, Ghandi M, Greulich H, Vazquez F, Weir BA, Van Allen EM, Tsherniak A, Shao DD, Zack TI, Noble M, Getz G, Beroukhim R, Garraway LA, Ardakani M, Romualdi C, Sales G, Barbie DA, Boehm JS, Hahn WC, Mesirov JP, Tamayo P. Characterizing genomic alterations in cancer by complementary functional associations. Nat Biotechnol. 2016;34(5):539-46. doi: 10.1038/nbt.3527. PubMed PMID: 27088724; PMCID: PMC4868596.
Howard TP, Vazquez F, Tsherniak A, Hong AL, Rinne M, Aguirre AJ, Boehm JS, Hahn WC. Functional Genomic Characterization of Cancer Genomes. Cold Spring Harb Symp Quant Biol. 2016;81:237-46. doi: 10.1101/sqb.2016.81.031070. PubMed PMID: 27815544.
Aguirre AJ, Meyers RM, Weir BA, Vazquez F, Zhang CZ, Ben-David U, Cook A, Ha G, Harrington WF, Doshi MB, Kost-Alimova M, Gill S, Xu H, Ali LD, Jiang G, Pantel S, Lee Y, Goodale A, Cherniack AD, Oh C, Kryukov G, Cowley GS, Garraway LA, Stegmaier K, Roberts CW, Golub TR, Meyerson M, Root DE, Tsherniak A, Hahn WC. Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting. Cancer Discov. 2016;6(8):914-29. doi: 10.1158/2159-8290.CD-16-0154. PubMed PMID: 27260156; PMCID: PMC4972686.
