William C. Hahn, MD, PhD
Chief, Division of Molecular and Cellular Oncology
Director, Center for Cancer Genome Discovery
Associate Professor of Medicine, Harvard Medical School
Senior Associate Member, Broad Institute of Harvard and MIT
Office phone: 617-632-3155
Preferred contact method: email
View Physician Profile
Area of Research
Functional genomics and human cell transformation
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
BiographyDr. Hahn received his MD and PhD from Harvard Medical School in 1994. He then completed clinical training in internal medicine at Massachusetts General Hospital and medical oncology at DFCI. He conducted his postdoctoral studies with Dr. Robert Weinberg at the Whitehead Institute and joined the faculty of DFCI and Harvard Medical School in 2001.
- Elected to Association of American Physicians, 2013
- Ho-Am Laureate in Medicine, 2010
- Gill-Simonian Prize for Mentoring, 2008
- Elected to the American Society of Clinical Investigation, 2005
- Wilson S. Stone Memorial Award, MD Anderson Cancer Center, 2000
ResearchFunctional genomics and human cell transformation
My work as a physician-scientist involves both the care of cancer patients and biomedical research directed toward a greater understanding of the mechanisms involved in malignant transformation. My laboratory 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 methods to perform systematic interrogation of gene function in mammalian cells and tissues and help optimize new approaches to integrate genome scale data. Using these approaches, we have identified and credential new oncogenes and tumor suppressor genes and have performed preclinical studies that will form the foundation necessary for translational studies in patients.
Specifically, we have developed genetic methods that permit the construction of genetically defined, experimental models of the major human epithelial cancers from primary human cells through the manipulation of oncogenes, tumor suppressor genes and telomerase. These model systems have permitted us to study the molecular interactions that lead to cancer. In addition, we have performed proof-of-principle experiments that such experimental models will prove useful in the discovery and validation of molecularly targeted therapies. Indeed, these experimental models have allowed us to investigate the mechanisms by which EGFR and other oncogenes and tumor suppressors contribute to cancer initiation. In particular, we have elucidated the role of the PP2A family of serine-threonine phosphatases as tumor suppressor genes.
As a Senior Associate Member of the Broad Institute, I lead efforts to apply functional genomic approaches to cancer. Specifically, I serve as one of the co-principal investigators for the RNAi Consortium (TRC), which has created a genome scale RNA interference library, and have established RNAi screening facilities at both the Broad Institute and the Dana-Farber Cancer Institute (DFCI). In my own laboratory, we are engaged in using these RNAi libraries to apply a comprehensive program to identify cancer vulnerabilities. Using these approaches, we have already discovered several new oncogenes including IKBKE, CDK8, CRKL, CDK6, and PAK1. I also co-direct the Center for Cancer Genome Discovery, which is committed to the development and implementation of technologies that permit the interrogation of cancer-associated mutations at genome scale and to implement these technologies prospectively in newly diagnosed patients.
- Sablina AA, Chen W, Arroyo JD, Corral L, Hector M, Bulmer SE, DeCaprio JA, Hahn WC. The tumor suppressor PP2A Aβ regulates the RalA GTPase. Cell. 2007; 129:969-82.
- 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; 129:1065-1079.
- Firestein R, Bass AJ, Kim SY, Dunn IF, Silver SJ, Guney I, Freed E, Ligon AH, Vena N, Ogino SJ, Chheda MG, Tamayo P, Finn S, Shrestha Y, Boehm JS, Jain S, Bojarski E, Mermel C, Barretina J, Chan JA, Baselga J, Tabernero J, Root DE, Fuchs CS, Loda M, Shivdasani RA, Meyerson M, Hahn WC. CDK8 is a colorectal cancer oncogene that regulates β-catenin activity. Nature. 2008; 455:547-51.
- Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C, Frhling S, Chan EM, Sos ML, Michel K, Mermel C, Silver SJ, Weir BA, Reiling JH, Sheng Q, Gupta PB, Wadlow RC, Le H, Hoersch S, Wittner BS, Ramaswamy S, Livingston DM, Sabatini DM, Meyerson M, Thomas RK, Lander ES, Mesirov JP, Root DE, Gilliland DG, Jacks T, Hahn WC. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009 462:108-12.
- Nijhawan D, Zack TI, Ren Y, Strickland MR, Lamothe R, Schumacher SE, Tsherniak A, Besche, HC, Rosenbluh J, Shehata S, Cowley GS, Weir BA, Goldberg AL, Mesirov JP, Root DE, Bhatia SN, Beroukhim R, Hahn WC. Cancer vulnerabilities unveiled by genomic loss. Cell. 2012; 150:842-54.
- Rosenbluh J, Nijhawan D, Cox AG, Li X, Neal JT, Schafer EJ, Zack TI, Wang X, Tsherniak A, Schinzel AC, Shao DD, Schumacher SE, Weir BA, Vazquez F, Cowley GS, Root DE, Mesirov JP, Beroukhim R, Kuo CJ, Goessling W, Hahn WC. β-catenin driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell. 2012; 151:1457–73.
- Rosenbluh, Sefi, PhD
- Takeda, David, MD, PhD
- Schinzel, Anna C, PhD
- Vazquez, Francesca, PhD
- Brastianos, Priscilla, MD
- Rinne, Mikael, MD, PhD
- Moody, Susan E., MD, PhD
- Choudhury, Atish D., MD, PhD
- Chheda, Milan, MD
- Boehm, Jesse, PhD (Scientist)
- Weir, Barbara, PhD (Scientist)
- Hagerstrand, Daniel, PhD
- Wang, Xiaoxing, PhD
- Shao, Diane, BS (MD-PhD student)
- O'Connell, Joyce T, PhD
- Ilic, Nina, PhD
- Hong, Andrew, MD
- Spardy, Nicole, PhD
- Aguirre, Andrew, MD, PhD
- Zwang, Yaara, PhD
- Krall, Elsa B, PhD
- Giacomelli, Andrew, MS (grad student)
- Wang, Belinda, BS (MD-PhD student)
- Kim, Eejung, MD (grad student)
- Abudayyeh, Omar, BS (MD-PhD student)
- Li, Ji, PhD