Research Department

Medical Oncology/Molecular and Cellular

Interest

Prostate cancer

Area of Research

Biography

Dr. 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.

Recent Awards

• Elected to the American Society of Clinical Investigation, 2005
• Kimmel Scholar Award, 2002
• Howard Temin Award, National Cancer Institute, 2001
• Doris Duke Charitable Foundation Clinical Scientist Development Award, 2000
• Wilson S. Stone Memorial Award, MD Anderson Cancer Center, 2000

Research

Our laboratory is interested in the cooperative interactions that conspire to transform human cells. Our prior work addressed the regulation of cellular lifespan in normal and malignant human cells. Both cell-cycle-regulatory proteins and telomerase 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.
We continue to characterize these model systems to understand the molecular interactions that lead to transformation. In particular, we have created new model systems that incorporate genes found mutated in specific human cancers (breast, prostate, lung) and have developed improved transplantation techniques that permit the recreation of a human microenvironment surrounding the tumor. We have also made immortalized, nontumorigenic epithelial cells that retain much of their epithelial markers and ability to differentiate; we will use these cells to investigate normal epithelial cell biology.
In parallel to these studies, we continue to investigate the pathways perturbed by telomerase and SV40 small t antigen in human cell transformation. Our recent work in telomere biology focuses on a new function of telomerase in transformation distinct from its role in immortalization. In addition, we have shown that SV40 small t antigen contributes to transformation by perturbing the serine-threonine phosphatase PP2A, and we are studying the consequences of this interaction for transformation. Finally, our lab is a founding member of a consortium dedicated to the production, validation, and use of genome-scale RNA interference reagents. Ultimately, these approaches will permit us to gain a greater understanding of the genetic changes that lead to cancer.

Select Publications

• 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;Mar 24;124(6):1283-98.
  
• 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.
• Scholl C, Frhling S, Dunn IF, Schinzel AC, Barbie DA, Kim SY, Silver SJ, Tamayo P, Wadlow RC, Ramaswamy S, Dhner K, Bullinger L, Sandy P, Boehm JS, Root DE, Jacks T, Hahn WC, Gilliland DG. Synthetic lethal interaction between oncogenic KRAS dependency and suppression of STK33 in human cancer cells. Cell. 2009; 137:821-34. Corresponding authors.
• 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.

Investigators

• Barbie, David, MD
• Xiang, Shi-Hua, Ph.D.
• Chheda, Milan, MD
• Boehm, Jesse, PhD (Scientist)
• Weir, Barbara, PhD (Scientist)

Trainees

• Cheung, Hiu Wing, PhD
• Schinzel, Anna, PhD
• Shen, Rhine, PhD
• Hagerstrand, Daniel, PhD
• Rosenbluh, Sefi, PhD
• Nguyen, Christine, PhD
• Nijhawan, Deepak, MD, PhD
• Choudhury, Atish, MD, PhD
• Moody, Susan, MD, PhD
• Dunn, Gavin, MD, PhD
• Wang, Xiaoxing, PhD
• Mashima, Tetsuo, PhD
• Shrestha, Yashaswi, BS (grad student)
• Zhou, Alicia, BS (grad student)
• Lee, Daniel, MD (grad student)
• Shao, Diane, BS (grad student)