William C. Hahn
Department of Medicine
Dana-Farber Cancer Institute
Department of Medical Oncology
Dana 1538
44 Binney Street
Boston, MA 02115
Tel: (617) 632-2641
Fax: (617) 632-4005
Email: William_Hahn@dfci.harvard.edu
Web Page: The Hahn Lab Page
12 postdoctoral fellows, 4 graduate students
Our research interests focus on understanding the cooperative interactions that transform normal human epithelial cells to cancer cells. Our prior work has addressed the regulation of cellular lifespan in both normal and malignant human cells. Cell cycle regulatory proteins and telomerase each regulate replicative lifespan, and alterations in each of these mechanisms are commonly found in human cancers. Telomerase plays a key role in cellular immortalization; expression of telomerase in many cells is sufficient to achieve immortalization, a hallmark of cancer. Using telomerase to immortalize human cells, we have shown that such immortalized cells are now susceptible to transformation by the combination of oncogene activation and inactivation of tumor suppressor pathways in vitro. Using oncogenes, dominant inhibitors of tumor suppressor proteins, and telomerase, we have created models of human breast, lung, prostate, and ovarian epithelial cancers of defined genetic constitution and have used these cell lines to study the roles of specific molecules and pathways in cell transformation. In particular, we have been studying non-telomeric functions of telomerase and the function of the serine-threonine phosphatase PP2A.
More recently, we have developed a series of new genetic tools to allow us to readily manipulate genes in mammalian cells. Using large-scale functional approaches including RNAi and ORF expression studies, we are engaged in studies to discover and validate new oncogenes and tumor suppressor genes that contribute to cancer initiation and maintenance. Ultimately, by combining these approaches will permit us to gain a deeper understanding of the networks that drive malignant transformation.
References:
- Masutomi K, Possemato R, Wong JMY, Currier JL, Tothova Z, Manola JB, Ganesan S, Lansdorp PM, Collins K, Hahn WC. The telomerase reverse transcriptase regulates chromatin state and DNA damage responses. Proc Natl Acad Sci. U.S.A. 2005, 102:8222-8227.
- Moffat J, Grueneberg DA, Yang X, Kim SY, Kloepfer AM, Hinkle G, Piqani B, Eisenhaure TM, Luo B, Grenier JK, Carpenter AE, Foo SY, Stewart SA, Stockwell BR, *Hacohen N, *Hahn WC, *Lander ES, *Sabatini DM, *Root DE. A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 2006, 124:1283-1298. *These authors contributed equally as senior authors.
- Sablina AA, Chen W, Arroyo JD, Corral L, Hector M, Bulmer SE, DeCaprio JA, Hahn WC. The tumor suppressor PP2A Ab regulates the RalA GTPase. Cell. 2007, 129(5):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(6):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, 455:547-557.
BBS webpage updated 12/02/2009