Ben Ho Park, M.D., Ph.D.
Associate Professor of Oncology
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Joint Appointment, Whiting School of Engineering, Department of Chemical and Biomolecular Engineering
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Room 1M42, Cancer Research Building 1
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The ultimate research goal of the Park Laboratory is to discover and develop novel means for treating breast cancer. The lab is developing techniques to identify genes involved with hormonal and chemotherapeutic drug resistance, as well as analyzing the genetic effectors of growth and hormone receptor mediated breast carcinogenesis.
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Using powerful molecular genetic techniques, the lab is identifying genes whose biallelic inactivation leads to clinical drug resistance. It has been previously demonstrated that loss of tumor suppressor genes and/or their downstream effectors can confer resistance against certain chemotherapies. The lab hypothesizes that there are other genes whose inactivation in a recessive manner can also lead to clinically relevant drug resistance. This problem is of extreme importance to clinical oncology, as the emergence of drug resistant cancers is what limits the effectiveness of current therapies.
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The lab is also trying to understand pathogenic mechanisms of growth/hormone receptor signaling. The continuous exposure of breast tissue to estrogens and other growth factors likely plays a role in the carcinogenic process that transforms a normal breast epithelial cell into a cancer. The lab is trying to elucidate the molecular mechanisms of aberrant receptor signaling that contributes to this process.
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- Park BH, Vogelstein B, Kinzler K. Genetic Disruption of PPAR Delta Decreases the Tumorigenicity of Human Colon Cancer Cells. Proceedings of the National Academy of Science, U.S.A. 98:2598-2603, 2001.
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- Rhee I, Bachmann KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, Vogelstein B. DNMT1 and DNMT3B Cooperate to Silence Genes in Human Cancer Cells. Nature 416:552-556, 2002.
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- Bachman KE,* Park BH,* Rhee I, Rajagopalan H, Herman JG, Baylin SB, Kinzler KW and Vogelstein B. The role of histone codes and DNA methylation in silencing tumor suppressor genes, Cancer Cell 3:89-95, 2003. *Contributed equally to this work.
- Bachman KE, Blair BG, Brenner K, Bardelli A, Arena S, Zhou S, Hicks J, De Marzo AM, Argani P and Park BH. p21 mediates the growth response to TGF-beta in human epithelial cells, Cancer Biology and Therapy, 3:221-225, 2004
- Bachman KE , Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B, Blair BG, Lin C, Peters BA, Velculescu VE and Park BH. The PIK3CA gene is mutated with high frequency in human breast cancers, Cancer Biology and Therapy 3:772-775, 2004.
- Bachman KE, Sager J, Cheong I, Catto M, Bardelli A, Park BH, Vogelstein B, Carotti A, Kinzler KW and Lengauer C. Identification of compounds that inhibit growth of PhIP resistant cancer cells, Molecular Cancer Therapeutics, 4(6):1026-30, Jun 2005.
- Keen JC, Zhou Q, Park BH, Pettit C, Mack KM, Blair B, Brenner K and Davidson NE. Protein phosphatase 2A (PP2A) regulates estrogen receptor alpha (ER) expression through modulation of ER mRNA stability, J. Biol. Chem. 280(33):29519-24, Aug.19 2005.
- Huang Y, Keen JC, Pledgie A, Marton LJ, Zhu T, Sukumar S, Park BH, Blair B, Brenner K, Casero RA Jr, Davidson NE. Polyamine analogues down-regulate estrogen receptor alpha expression in human breast cancer cells. J. Biol. Chem. 281(28):19055-63, Jul 14, 2006.
- Abukhdeir AM, Blair BG, Brenner K, Karakas B, Konishi H, Lim J, Sahasranaman V, Huang Y, Keen J, Davidson N, Vitolo MI, Bachman KE, and Park BH. Physiologic Estrogen Receptor Alpha Signaling in Non-tumorigenic Human Mammary Epithelial Cells, Breast Cancer Res Treat, 99(1):23-33, Sept. 2006.
- Karakas B, Weeraratna A, Abukhdeir A, Blair BG, Konishi H, Arena S, Becker K, Wood W, Argani P, De Marzo AM, Bachman KE and Park BH. Interleukin-1 alpha mediates the growth proliferative effects of transforming growth factor-beta in p21 null MCF-10A human mammary epithelial cells, Oncogene, 25(40):5561-9, Sep 7, 2006.
- Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber T, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The Consensus Coding Sequences of Human Breast and Colorectal Cancers, Science, Oct 13;314(5797):268-74, 2006.
- Weiss M.B., Vitolo M.I., Baerenfaller K., Marra G., Park B.H., Bachman K.E. Persistent mismatch repair deficiency following targeted correction of hMLH1. Cancer Gene Therapy, Jan;14(1):98-104, 2007.
- Karakas B, Weeraratna A, Abukhdeir A, Konishi H, Gustin J, Vitolo MI, Bachman KE, Park BH. p21 gene knock down does not identify genetic effectors seen with gene knock out, Cancer Biology and Therapy, Mar 26;6(7) 2007.
- Sui M, Huang Y, Park BH, Davidson NE, Fan W. Estrogen Receptor α Mediates Breast Cancer Cells Resistance to Paclitaxel through Inhibition of Apoptotic Cell Death, Cancer Research, Jun 1;67(11):5337-44, 2007.
- Konishi H, Karakas B, Abukhdeir AM, Lauring J, Gustin JP, Garay JP, Konishi Y, Gallmeier Y, Bachman KE, Park BH. Knock in of mutant K-ras in non-tumorigenic human epithelial cells as a new model for studying K-ras mediated transformation, Cancer Research Sep15;67(18):8460-7, 2007.
- Konishi H, Lauring J, Garay JP, Karakas B, Abukhdeir AM, Gustin JP, Konishi Y, Park BH. A PCR-based high-throughput screen with multi-round sample pooling: application to somatic cell gene targeting, Nature Protocols 2(11):2865-74, 2007.
- Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J, Silliman N, Szabo S, Dezso Z, Ustyanksky V, Nikolskaya T, Nikolsky Y, Karchin R, Wilson PA, Kaminker JS, Zhang Z, Croshaw R, Willis J, Dawson D, Shipitsin M, Willson JK, Sukumar S, Polyak K, Park BH, Pethiyagoda CL, Pant PV, Ballinger DG, Sparks AB, Hartigan J, Smith DR, Suh E, Papadopoulos N, Buckhaults P, Markowitz SD, Parmigiani G, Kinzler KW, Velculescu VE, Vogelstein B. The genomic landscapes of human breast and colorectal cancers, Science Nov 16;318(5853):1108-13, 2007.
- Lauring J, Abukhdeir AM, Konishi H, Garay JP, Gustin JP, Wang Q, Arceci RJ, Matsui M and Park BH. The multiple myeloma-associated MMSET gene contributes to cellular adhesion, clonogenic growth, and tumorigenicity, Blood Jan 15;111(2):856-64, 2008.
- Abukhdeir A, Vitolo M, Argani P, De Marzo AM, Karakas B, Konishi H, Gustin J, Lauring J, Garay J, Pendleton C, Konishi Y, Blair BG, Brenner K, Garrett-Mayer E, Carraway H, Bachman KE, Park BH. Tamoxifen stimulated growth of breast cancer due to p21 loss, Proceedings of the National Academy of Science, U.S.A. Jan 8;105(1):288-93, 2008.
- Leary R, Lin J, Cummins J, Boca S, Wood L, Parsons D, Jones S, Sjoblom T, Park BH, Parsons R, Willis J, Dawson D, Willson J, Nikolskaya T ,Nikolsky Y, Kopelovich L, Papadopoulos N, Pennacchio L, Wang TL, Markowitz S, Parmigiani G, Kinzler K, Vogelstein B and Velculescu V. Dramatic changes in copy number are a major mechanism for gene activation and inactivation in breast and colorectal cancers, Proceedings of the National Academy of Science, U.S.A. Oct 21;105(42):16224-9, 2008.
- Hansel DE, Nakayama M, Luo J, Abukhdeir AM, Park BH, Bieberich CJ, Hicks JL, Eisenberger M, Nelson WG, Mostwin JL, De Marzo AM. Shared TP53 gene mutation in morphologically and phenotypically distinct concurrent primary small cell neuroendocrine carcinoma and adenocarcinoma of the prostate. Prostate 2009 Jan 5. [Epub ahead of print]
- Gustin JP, Karakas B, Weiss MB, Abukhdeir AM, Lauring J, Garay JP, Cosgrove D, Tamaki A, Konishi H, Konishi Y, Mohseni M, Wang G, Rosen DM, Denmeade SR, Higgins MJ, Vitolo MI, Bachman KE, Park BH. Knock in of mutant PIK3CA activates multiple oncogenic pathways. Proceedings of the National Academy of Science, U.S.A, Feb 24;106(8):2835-40, 2009.
- Karnan S, Mohseni M, Konishi Y, Tamaki A, Hosokawa Y, Park BH*, Konishi H*. Controversial BRCA1 allelotypes in commonly used breast cancer cell lines. Breast Cancer Res Treat. 2009 Jul 8. [Epub ahead of print]. *Co-corresponding author.
- Vitolo MI, Weiss MB, Szmacinski M, Tahir K, Waldman T, Park BH, Martin SS, Weber DJ, Bachman KE. Deletion of PTEN promotes tumorigenic signaling, resistance to anoikis, and altered response to chemotherapeutic agents in Human Mammary Epithelial Cells. Cancer Research, in press 2009.