DF/HCC Program Affiliation

Cancer Cell Biology
Prostate Cancer

Research Abstract

As a physician-scientist, my research interests focus on gaining a greater understanding of the fundamental mechanisms that change a normal cell into a malignant cancer. My laboratory has developed experimental cancer models of defined genetic constitution and genome scale tools to perform gain and loss of function genetics in human cells. We are using these systems to derive a global understanding of cancer vulnerabillities. My clinical interests are in genitourinary oncology (prostate, renal, and bladder cancers).

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 g
  16564017
• Chen W, Arroyo JD, Timmons JC, Possemato R, Hahn WC.Cancer-associated PP2A Aalpha subunits induce functional haploinsufficiency and tumorigenicity.Cancer Res 2005 Sep 15;65(18):8183-92.
  16166293
• Masutomi K, Possemato R, Wong JM, 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 Jun 7;102(23):8222-7.
  15928077
• Berger R, Febbo PG, Majumder PK, Zhao JJ, Mukherjee S, Signoretti S, Campbell KT, Sellers WR, Roberts TM, Loda M, Golub TR, Hahn WC.Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells.Cancer Res 2004 Dec 15;64(24):8867-7
  15604246
• Chen W, Possemato R, Campbell KT, Plattner CA, Pallas DC, Hahn WC.Identification of specific PP2A complexes involved in human cell transformation.Cancer Cell 2004 Feb;5(2):127-36.
  14998489
• Masutomi K, Yu EY, Khurts S, Ben-Porath I, Currier JL, Metz GB, Brooks MW, Kaneko S, Murakami S, DeCaprio JA, Weinberg RA, Stewart SA, Hahn WC.Telomerase maintains telomere structure in normal human cells.Cell 2003 Jul 25;114(2):241-53.
  12887925
• Zhao JJ, Gjoerup OV, Subramanian RR, Cheng Y, Chen W, Roberts TM, Hahn WC.Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase.Cancer Cell 2003 May;3(5):483-95.
  12781366
• Stewart SA, Dykxhoorn DM, Palliser D, Mizuno H, Yu EY, An DS, Sabatini DM, Chen IS, Hahn WC, Sharp PA, Weinberg RA, Novina CD.Lentivirus-delivered stable gene silencing by RNAi in primary cells.RNA 2003 Apr;9(4):493-501.
  12649500
• Stewart SA, Hahn WC, O'Connor BF, Banner EN, Lundberg AS, Modha P, Mizuno H, Brooks MW, Fleming M, Zimonjic DB, Popescu NC, Weinberg RA.Telomerase contributes to tumorigenesis by a telomere length-independent mechanism.Proc Natl Acad Sci U S A 2002 Oct 1;
  12193655
• Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA.Creation of human tumour cells with defined genetic elements.Nature 1999 Jul 29;400(6743):464-8.
  10440377
• Hu M, Yao J, Carroll DK, Weremowicz S, Chen H, Carrasco D, Richardson A, Violette S, Nikolskaya T, Nikolsky Y, Bauerlein EL, Hahn WC, Gelman RS, Allred C, Bissell MJ, Schnitt S, Polyak K.Regulation of in situ to invasive breast carcinoma transition.Cancer
  18455123
• Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, Bhimavarapu A, Luikenhuis S, de Cabo R, Fuchs C, Hahn WC, Guarente LP, Sinclair DA.The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.PLoS ONE 2008;3(4):
  18414679
• Wiedemeyer R, Brennan C, Heffernan TP, Xiao Y, Mahoney J, Protopopov A, Zheng H, Bignell G, Furnari F, Cavenee WK, Hahn WC, Ichimura K, Collins VP, Chu GC, Stratton MR, Ligon KL, Futreal PA, Chin L.Feedback circuit among INK4 tumor suppressors constrains
  18394558
• Westermarck J, Hahn WC.Multiple pathways regulated by the tumor suppressor PP2A in transformation.Trends Mol Med 2008 Apr;14(4):152-60.
  18329957
• Arroyo JD, Lee GM, Hahn WC.Liprin alpha1 interacts with PP2A B56gamma.Cell Cycle 2007 Nov 30;7(4).
  18235218
• Lee J, Sung YH, Cheong C, Choi YS, Jeon HK, Sun W, Hahn WC, Ishikawa F, Lee HW.TERT promotes cellular and organismal survival independently of telomerase activity.Oncogene 2008 Jan 28.
  18223679
• Sablina AA, Hahn WC.SV40 small T antigen and PP2A phosphatase in cell transformation.Cancer Metastasis Rev 2008 Jan 23.
  18214640
• Pienta KJ, Abate-Shen C, Agus DB, Attar RM, Chung LW, Greenberg NM, Hahn WC, Isaacs JT, Navone NM, Peehl DM, Simons JW, Solit DB, Soule HR, Vandyke TA, Weber MJ, Wu L, Vessella RL.The current state of preclinical prostate cancer animal models.Prostate 200
  18213636
• Schinzel AC, Hahn WC.Oncogenic transformation and experimental models of human cancer.Front Biosci 2008;13:71-84.
  17981529
• Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK.Malignant astrocytic glioma: genetics, biology, and paths to treatment.Genes Dev 2007 Nov 1;21(21):2683-710.
  17974913
• Cho US, Morrone S, Sablina AA, Arroyo JD, Hahn WC, Xu W.Structural basis of PP2A inhibition by small t antigen.PLoS Biol 2007 Aug;5(8):e202.
  17608567
• 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, Rober
  17574021
• Sablina AA, Chen W, Arroyo JD, Corral L, Hector M, Bulmer SE, Decaprio JA, Hahn WC.The Tumor Suppressor PP2A Abeta Regulates the RalA GTPase.Cell 2007 Jun 1;129(5):969-982.
  17540176
• Park Y, Downing SR, Kim D, Hahn WC, Li C, Kantoff PW, Wei LJ.Simultaneous and exact interval estimates for the contrast of two groups based on an extremely high dimensional variable: Application to Mass Spec data.Bioinformatics 2007 Apr 25.
  17459967
• Kim SY, Hahn WC.Cancer Genomics: Integrating Form and Function.Carcinogenesis 2007 Apr 17.
  17434922
• Nieto M, Finn S, Loda M, Hahn WC.Prostate cancer: Re-focusing on androgen receptor signaling.Int J Biochem Cell Biol 2007 Jan 20.
  17321194
• Margolis SS, Perry JA, Forester CM, Nutt LK, Guo Y, Jardim MJ, Thomenius MJ, Freel CD, Darbandi R, Ahn JH, Arroyo JD, Wang XF, Shenolikar S, Nairn AC, Dunphy WG, Hahn WC, Virshup DM, Kornbluth S.Role for the PP2A/B56delta phosphatase in regulating 14-3-3
  17110335
• Hieronymus H, Lamb J, Ross KN, Peng XP, Clement C, Rodina A, Nieto M, Du J, Stegmaier K, Raj SM, Maloney KN, Clardy J, Hahn WC, Chiosis G, Golub TR.Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modul
  17010675
• Echeverri CJ, Beachy PA, Baum B, Boutros M, Buchholz F, Chanda SK, Downward J, Ellenberg J, Fraser AG, Hacohen N, Hahn WC, Jackson AL, Kiger A, Linsley PS, Lum L, Ma Y, Mathey-Prévôt B, Root DE, Sabatini DM, Taipale J, Perrimon N, Bernards R.Minimizing th
  16990807
• Root DE, Hacohen N, Hahn WC, Lander ES, Sabatini DM.Genome-scale loss-of-function screening with a lentiviral RNAi library.Nat Methods 2006 Sep;3(9):715-9.
  16929317
• Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG, Golub TR, Armstrong SA.Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9.Nature 2006 Jul 16.
  16862118
• Kim M, Gans JD, Nogueira C, Wang A, Paik JH, Feng B, Brennan C, Hahn WC, Cordon-Cardo C, Wagner SN, Flotte TJ, Duncan LM, Granter SR, Chin L.Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene.Cell 2006 Jun 30;125(7):1269-81.
  16814714
• Berger R, Lin DI, Nieto M, Sicinska E, Garraway LA, Adams H, Signoretti S, Hahn WC, Loda M.Androgen-dependent regulation of Her-2/neu in prostate cancer cells.Cancer Res 2006 Jun 1;66(11):5723-8.
  16740710
• Lin SS, Bassik MC, Suh H, Nishino M, Arroyo JD, Hahn WC, Korsmeyer SJ, Roberts TM.PP2A regulates BCL-2 phosphorylation and proteasome-mediated degradation at the endoplasmic reticulum.J Biol Chem 2006 May 22.
  16717086
• Polyak K, Hahn WC.Roots and stems: stem cells in cancer.Nat Med 2006 Mar;12(3):296-300.
  16520777
• Arroyo JD, Hahn WC.Involvement of PP2A in viral and cellular transformation.Oncogene 2005 Nov 21;24(52):7746-55.
  16299534
• Goessel G, Quante M, Hahn WC, Harada H, Heeg S, Suliman Y, Doebele M, von Werder A, Fulda C, Nakagawa H, Rustgi AK, Blum HE, Opitz OG.Creating oral squamous cancer cells: a cellular model of oral-esophageal carcinogenesis.Proc Natl Acad Sci U S A 2005 Oct
  16239349
• Yu EY, Hahn WC.The origin of cancer.Cancer Treat Res 2004;122:1-22.
  16209036
• Greulich H, Chen TH, Feng W, Jänne PA, Alvarez JV, Zappaterra M, Bulmer SE, Frank DA, Hahn WC, Sellers WR, Meyerson M.Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants.PLoS Med 2005 Oct 4;2(11):e313.
  16187797
• Sjostrom SK, Finn G, Hahn WC, Rowitch DH, Kenney AM.The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors.Dev Cell 2005 Sep;9(3):327-38.
  16139224
• Boehm JS, Hahn WC.Cancer genetics: Finding the right mix.Eur J Hum Genet 2005 Oct;13(10):1099-100.
  16077731
• Boehm JS, Hession MT, Bulmer SE, Hahn WC.Transformation of human and murine fibroblasts without viral oncoproteins.Mol Cell Biol 2005 Aug;25(15):6464-74.
  16024784
• Nakamura M, Masutomi K, Kyo S, Hashimoto M, Maida Y, Kanaya T, Tanaka M, Hahn WC, Inoue M.Efficient inhibition of human telomerase reverse transcriptase expression by RNA interference sensitizes cancer cells to ionizing radiation and chemotherapy.Hum Gene
  16000067
• Hahn WC.Telomere and telomerase dynamics in human cells.Curr Mol Med 2005 Mar;5(2):227-31.
  15974877
• Hashimoto M, Kyo S, Masutomi K, Maida Y, Sakaguchi J, Mizumoto Y, Nakamura M, Hahn WC, Inoue M.Analysis of telomeric single-strand overhang length in human endometrial cancers.FEBS Lett 2005 May 23;579(13):2959-64.
  15893755
• Yu EY, Hahn WC.Genetic alterations in prostate cancer.Clin Prostate Cancer 2005 Mar;3(4):220-9.
  15882478
• Dong CK, Masutomi K, Hahn WC.Telomerase: regulation, function and transformation.Crit Rev Oncol Hematol 2005 May;54(2):85-93.
  15843091
• Boehm JS, Hahn WC.Understanding transformation: progress and gaps.Curr Opin Genet Dev 2005 Feb;15(1):13-7.
  15661528
• Moreno CS, Ramachandran S, Ashby DG, Laycock N, Plattner CA, Chen W, Hahn WC, Pallas DC.Signaling and transcriptional changes critical for transformation of human cells by simian virus 40 small tumor antigen or protein phosphatase 2A B56gamma knockdown.Ca
  15466190
• Hahn WC.Cancer: surviving on the edge.Cancer Cell 2004 Sep;6(3):215-22.
  15380512
• Chiang YJ, Hemann MT, Hathcock KS, Tessarollo L, Feigenbaum L, Hahn WC, Hodes RJ.Expression of telomerase RNA template, but not telomerase reverse transcriptase, is limiting for telomere length maintenance in vivo.Mol Cell Biol 2004 Aug;24(16):7024-31.
  15282303
• Zhao JJ, Roberts TM, Hahn WC.Functional genetics and experimental models of human cancer.Trends Mol Med 2004 Jul;10(7):344-50.
  15242683
• Satyanarayana A, Greenberg RA, Schaetzlein S, Buer J, Masutomi K, Hahn WC, Zimmermann S, Martens U, Manns MP, Rudolph KL.Mitogen stimulation cooperates with telomere shortening to activate DNA damage responses and senescence signaling.Mol Cell Biol 2004 J
  15169907
• Yeh E, Cunningham M, Arnold H, Chasse D, Monteith T, Ivaldi G, Hahn WC, Stukenberg PT, Shenolikar S, Uchida T, Counter CM, Nevins JR, Means AR, Sears R.A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells
  15048125
• Liu J, Yang G, Thompson-Lanza JA, Glassman A, Hayes K, Patterson A, Marquez RT, Auersperg N, Yu Y, Hahn WC, Mills GB, Bast RC.A genetically defined model for human ovarian cancer.Cancer Res 2004 Mar 1;64(5):1655-63.
  14996724
• Vonderheide RH, Domchek SM, Schultze JL, George DJ, Hoar KM, Chen DY, Stephans KF, Masutomi K, Loda M, Xia Z, Anderson KS, Hahn WC, Nadler LM.Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes.Clin Cancer Res
  14871958
• Baykal A, Thompson JA, Xu XC, Hahn WC, Deavers MT, Malpica A, Gershenson DM, Silva EG, Liu J.In situ human telomerase reverse transcriptase expression pattern in normal and neoplastic ovarian tissues.Oncol Rep 2004 Feb;11(2):297-302.
  14719058
• Blasco MA, Hahn WC.Evolving views of telomerase and cancer.Trends Cell Biol 2003 Jun;13(6):289-94.
  12791294
• Hahn WC.Role of telomeres and telomerase in the pathogenesis of human cancer.J Clin Oncol 2003 May 15;21(10):2034-43.
  12743159
• Irwin MS, Kondo K, Marin MC, Cheng LS, Hahn WC, Kaelin WG.Chemosensitivity linked to p73 function.Cancer Cell 2003 Apr;3(4):403-10.
  12726865
• Dolma S, Lessnick SL, Hahn WC, Stockwell BR.Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.Cancer Cell 2003 Mar;3(3):285-96.
  12676586
• Wei W, Jobling WA, Chen W, Hahn WC, Sedivy JM.Abolition of cyclin-dependent kinase inhibitor p16Ink4a and p21Cip1/Waf1 functions permits Ras-induced anchorage-independent growth in telomerase-immortalized human fibroblasts.Mol Cell Biol 2003 Apr;23(8):285
  12665584
• Stewart SA, Ben-Porath I, Carey VJ, O'Connor BF, Hahn WC, Weinberg RA.Erosion of the telomeric single-strand overhang at replicative senescence.Nat Genet 2003 Apr;33(4):492-6.
  12652299
• Hahn WC, Weinberg RA.Rules for making human tumor cells.N Engl J Med 2002 Nov 14;347(20):1593-603.
  12432047
• Lundberg AS, Randell SH, Stewart SA, Elenbaas B, Hartwell KA, Brooks MW, Fleming MD, Olsen JC, Miller SW, Weinberg RA, Hahn WC.Immortalization and transformation of primary human airway epithelial cells by gene transfer.Oncogene 2002 Jul 4;21(29):4577-86.
  12085236
• Hahn WC, Dessain SK, Brooks MW, King JE, Elenbaas B, Sabatini DM, DeCaprio JA, Weinberg RA.Enumeration of the simian virus 40 early region elements necessary for human cell transformation.Mol Cell Biol 2002 Apr;22(7):2111-23.
  11884599
• Zimonjic D, Brooks MW, Popescu N, Weinberg RA, Hahn WC.Derivation of human tumor cells in vitro without widespread genomic instability.Cancer Res 2001 Dec 15;61(24):8838-44.
  11751406
• Vonderheide RH, Schultze JL, Anderson KS, Maecker B, Butler MO, Xia Z, Kuroda MJ, von Bergwelt-Baildon MS, Bedor MM, Hoar KM, Schnipper DR, Brooks MW, Letvin NL, Stephans KF, Wucherpfennig KW, Hahn WC, Nadler LM.Equivalent induction of telomerase-specific
  11731409
• Vonderheide RH, Anderson KS, Hahn WC, Butler MO, Schultze JL, Nadler LM.Characterization of HLA-A3-restricted cytotoxic T lymphocytes reactive against the widely expressed tumor antigen telomerase.Clin Cancer Res 2001 Nov;7(11):3343-8.
  11705846
• Johnson FB, Marciniak RA, McVey M, Stewart SA, Hahn WC, Guarente L.The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase.EMBO J 2001 Feb 15;20(4):905-13.
  11179234
• Elenbaas B, Spirio L, Koerner F, Fleming MD, Zimonjic DB, Donaher JL, Popescu NC, Hahn WC, Weinberg RA.Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells.Genes Dev 2001 Jan 1;15(1):50-65.
  11156605
• Lundberg AS, Hahn WC, Gupta P, Weinberg RA.Genes involved in senescence and immortalization.Curr Opin Cell Biol 2000 Dec;12(6):705-9.
  11063935
• Dickson MA, Hahn WC, Ino Y, Ronfard V, Wu JY, Weinberg RA, Louis DN, Li FP, Rheinwald JG.Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiat
  10648628
• Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen RL, Knoll JH, Meyerson M, Weinberg RA.Inhibition of telomerase limits the growth of human cancer cells.Nat Med 1999 Oct;5(10):1164-70.
  10502820
• Vonderheide RH, Hahn WC, Schultze JL, Nadler LM.The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes.Immunity 1999 Jun;10(6):673-9.
  10403642
• Counter CM, Hahn WC, Wei W, Caddle SD, Beijersbergen RL, Lansdorp PM, Sedivy JM, Weinberg RA.Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization.Proc Natl Acad Sci U S A 1998 Dec 8;95(25):14723-8.
  9843956
• Liu SJ, Hahn WC, Bierer BE, Golan DE.Intracellular mediators regulate CD2 lateral diffusion and cytoplasmic Ca2+ mobilization upon CD2-mediated T cell activation.Biophys J 1995 Feb;68(2):459-70.
  7696499
• Hahn WC, Bierer BE.Separable portions of the CD2 cytoplasmic domain involved in signaling and ligand avidity regulation.J Exp Med 1993 Nov 1;178(5):1831-6.
  7901319
• Hahn WC, Menzin E, Saito T, Germain RN, Bierer BE.The complete sequences of plasmids pFNeo and pMH-Neo: convenient expression vectors for high-level expression of eukaryotic genes in hematopoietic cell lines.Gene 1993 May 30;127(2):267-8.
  8500769
• Hahn WC, Burakoff SJ, Bierer BE.Signal transduction pathways involved in T cell receptor-induced regulation of CD2 avidity for CD58.J Immunol 1993 Apr 1;150(7):2607-19.
  7681075
• Hahn WC, Rosenstein Y, Calvo V, Burakoff SJ, Bierer BE.A distinct cytoplasmic domain of CD2 regulates ligand avidity and T-cell responsiveness to antigen.Proc Natl Acad Sci U S A 1992 Aug 1;89(15):7179-83.
  1353888
• Hahn WC, Menu E, Bothwell AL, Sims PJ, Bierer BE.Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59.Science 1992 Jun 26;256(5065):1805-7.
  1377404
• Rosenstein Y, Park JK, Hahn WC, Rosen FS, Bierer BE, Burakoff SJ.CD43, a molecule defective in Wiskott-Aldrich syndrome, binds ICAM-1.Nature 1991 Nov 21;354(6350):233-5.
  1683685
• Hahn WC, Rosenstein Y, Burakoff SJ, Bierer BE.Interaction of CD2 with its ligand lymphocyte function-associated antigen-3 induces adenosine 3',5'-cyclic monophosphate production in T lymphocytes.J Immunol 1991 Jul 1;147(1):14-21.
  1711070
• Cicila GT, O'Connell TM, Hahn WC, Rheinwald JG.Cloned cDNA sequence for the human mesothelial protein 'mesosecrin' discloses its identity as a plasminogen activator inhibitor (PAI-1) and a recent evolutionary change in transcript processing.J Cell Sci 198
  2613765
• Rheinwald JG, Jorgensen JL, Hahn WC, Terpstra AJ, O'Connell TM, Plummer KK.Mesosecrin: a secreted glycoprotein produced in abundance by human mesothelial, endothelial, and kidney epithelial cells in culture.J Cell Biol 1987 Feb;104(2):263-75.
  3543023