Ben Ho Park, M.D., Ph.D
Genetic approaches to breast cancer therapy
The 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 genetic effectors of breast carcinogenesis. Using powerful genetic technologies, genes involved with drug resistance and carcinogenesis are identified and validated and then novel therapeutics are developed against these newly identified targets. The lab is also developing new methods to measure residual cancer burden in patients using plasma tumor DNA and droplet digital PCR technologies.
- 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.
- 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.
- 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, 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 May 1;69(6):603-9, 2009.
- 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.
- 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, Nov 1;69(21):8275-83, 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. Jan;119(1):249-51, 2010. *Co-corresponding author.
- Lauring J, Cosgrove DP, Fontana S, Gustin JP, Konishi H, Abukhdeir AM, Garay JP, Mohseni M, Wang GM, Higgins MJ, Gorkin D, Reis M, Vogelstein B, Polyak K, Buckhaltz P, Park BH. Knock in of the AKT1 E17K hotspot mutation in human breast epithelial cells does not recapitulate the phenotype of oncogenic PIK3CA mutations, Oncogene Apr 22;29(16):2337-45, 2010.
- Weiss MB, Vitolo MI, Mohseni M, Rosen DM, Denmeade SR, Park BH*, Weber DJ*, Bachman KE*. Deletion of p53 in human mammary epithelial cells causes chromosomal instability and altered therapeutic response, Oncogene, Aug 19;29(33):4715-24, 2010. *Co-corresponding author.
- Colak D, Chisti MA, Al-Bakheet A, Al-Qahtani A, Shoukri MM, Goyns MH, Ozand PT, Quackenbush J, Park BH, Kaya N. Integrative and Comparative Genomics Analysis of Early Hepatocellular Carcinoma Differentiated from Liver Regeneration in Young and Old, Molecular Cancer, Jun 12;9:146, 2010.
- Higgins MJ, Beaver JA, Wong HY, Gustin JP, Lauring J, Cosgrove DP, Garay JP, Konishi H, Tamaki A, Mohseni M, Wang GM, Cidado J, Jelovac D, Abukhdeir AM, Park BH. PIK3CA mutations and EGFR overexpression predict for lithium sensitivity in human breast epithelial cells, Cancer Biology and Therapy, Feb 1;11(3):35-44, 2011.
- Lewis GH, Subhawong AP, Nassar H, Vang R, Illei P, Park BH, and Argani P. Relationship between Molecular Subtype of Invasive Breast Carcinoma (IBC) and Expression of Gross Cystic Disease Fluid Protein 15 (GCDFP) and Mammaglobin (MGB), American Journal of Clinical Pathology, Apr;135(4):587-91, 2011.
- Li H, Keeton A, Maddox C, Rasmussen L, Hobrath J, White EL, Piazza GA, Kim JS, Vitolo M, Park BH, Waldman T. A High Throughput Screen with Isogenic PTEN+/+ and PTEN-/- Cells Identifies CID1340132 As a Novel Compound That Induces Apoptosis in PTEN and PIK3CA Mutant Human Cancer Cells, J Biomol Screen, Apr;16(4):383-93, 2011.
- Lotan TL, Gurel B, Sutcliffe S, Esopi D, Liu W, Xu J, Hicks JL, Park BH, Humphreys E, Partin AW, Han M, Netto GJ, Isaacs WB, De Marzo AM.PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients, Clin Cancer Res. Oct 15;17(20):6563-73, 2011.
- Konishi H, Mohseni M, Tamaki A, Garay JP, Croessmann S, Karnan S, Ota A, Wong HY, Konishi Y, Karakas B, Tahir, K, Abukhdeir AM, Gustin JP, Cidado J, Wang GM, Cosgrove D, Cochran R, Jelovac D, Higgins MJ, Arena S, Hawkins L, Lauring J, Gross AL, Heaphy C, Hosokawa Y, Gabrielson E, Meeker A, Visvanathan K, Argani P, Bachman KE, Park BH. Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cell, Proceedings of the National Academy of Science, U.S.A, Oct 25;108(43):17773-8, 2011.
- Kuo AJ, Cheung P, Chen K, Zee BM, Kioi M, Lauring J, Xi Y, Park BH, Shi X, Garcie BA, Li W, Gozani O. NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming, Molecular Cell, Nov 18;44(4):609-20, 2011.
- Cimino-Mathews A, Hicks JL, Illei PB, Halushka MK, Fetting JH, De Marzo AM, Park BH, Argani P. Androgen receptor expression is usually maintained in initial surgically resected breast cancer metastases but is often lost in end-stage metastases found at autopsy. Human Pathology, Jul;43(7):1003-11, 2012.
- Garay JP, Karakas B, Abukhdeir AM, Cosgrove DP, Gustin JP, Higgins MJ, Konishi H, Konishi Y, Lauring J, Mohseni M, Wang GM, Jelovac D, Weeraratna A, Sherman Baust CA, Morin PJ, Toubaji A, Meeker A, De Marzo AM, Lewis G, Subhawong A, Argani P, Park BH. The growth response to androgen receptor signaling in ER negative human breast cells is dependent on p21 and mediated by MAP kinase activation, Breast Cancer Research, Feb 9;14(1):R27, 2012.
- Higgins MJ, Jelovac D, Barnathan E, Blair B, Slater S, Powers P, Zorzi J, Jeter SC, Oliver GR, Diehl F, Angenendt P, Huang P, Cope L, Argani P, Murphy KM, Bachman KE, Greshock J, Wolff AC, Park BH. Detection of tumor PIK3CA status in Metastatic Breast Cancer using Peripheral Blood and Implications for Targeted Therapy, Clinical Cancer Research, Jun 15;18(12):3462-9, 2012.
- Hurley PJ, Marchionni L, Simons BW, Ross AE, Peskoe SB, Miller RM, Erho N, Vergara IA, Ghadessi M, Huang Z, Gurel B, Park BH, Davicioni E, Jenkins RB, Platz EA, Berman DM, Schaeffer EM. Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome, Proceedings of the National Academy of Science, U.S.A, Sep 11;109(37):14977-82, 2012.
- Cimino-Mathews A, Subhawong AP, Elwood H, Nassar H, Sharma R, Park BH, Taube J, Illei PB, Argani P. Neural crest transcription factor Sox10 is preferentially expressed in triple negative and metaplastic breast carcinomas, Human Pathology, Jun;44(6):959-65, 2013.
- Jin L, Hanigan CL, Wu Y, Wang W, Park BH, Woster PM, Casero RC. Loss of LSD1 (lysine-specific demethylase 1) suppresses growth and alters gene expression of human colon cancer cells in a p53- and DNMT1(DNA methyltransferase 1)-independent manner.Biochemical Journal, Jan 15;449(2):459-68, 2013.
- Cimino-Mathews A, Subhawong AP, Elwood H, Nassar H, Sharma R, Park BH, Taube J, Illei PB, Argani P. GATA3 Expression in Breast Carcinoma: Utility in Triple Negative, Sarcomatoid and Metastatic Carcinomas, Human Pathology, Jul;44(7):1341-9, 2013.
- Wang GM, Wong HY, Konishi H, Abukhdeir A, Gustin JP, Rosen M, Denmeade S, Rasheed Z, Matsui W, Garay JP, Mohseni M, Higgins MJ, Cidado J, Jelovac D, Croessmann S, Cochran R, Karnan S, Hosokawa Y, Argani P, Lauring J, Park BH. A single mutant KRAS allele cooperates with mutant PIK3CA in human epithelial cells to induce transformation, Cancer Research, Jun 1;73(11):3248-61, 2013.
- Colak D, Nofal A, Nirmal M, Jeprel H, AlBakheet A, Eldali A, AL-Tweigeri T, Tulbah A, Ajarim D, Al Malik O, Inan MS , Kaya N, Park BH, Bin Amer SM. Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women , PLOS One, May 21;8(5):e63204, 2013.
- Ghosh S, Varela L, Sood A, Park BH, and Lotan T. mTOR Signaling Feedback Modulates Mammary Epithelial Differentiation and Restrains Invasion Downstream of PTEN Loss, Cancer Research, 2013 in press.
- Beaver JA, Gustin JP, Yi KH, Rajpurohit A, Thomas M, Gilbert SF, Rosen DM, Park BH, Lauring J. PIK3CA and AKT1 mutations have distinct effects on sensitivity to targeted pathway inhibitors in an isogenic luminal breast cancer model system, Clin Cancer Res. 2013 in press.
- Forde PM, MD1, Cochran RL, Boikos SA, Zabransky DJ, Beaver JA, MeyerCF, Thornton KA, Montgomery EA, Lidor AO, Donehower RC and Park BH. Familial Gastrointestinal Stromal Tumor with Loss-of-Heterozygosity and Amplification of Mutant KIT, J.Clin.Oncol. 2013, in press.
- Karakas B, Colak D, Kaya N, Ghebeh H, Al-Qasem A, Hendrayan F, Toulimat M, Al-Tweigeri T, Park BH, Aboussekhra A. Prevalence of PIK3CA Mutations and the SNP rs17849079 in Arab Breast Cancer Patients, Cancer Biology and Therapy, 2013, in press.