• Researcher Profile

    Ronny I. Drapkin, MD, PhD

     
    Ronny I. Drapkin, MD, PhD
     
    Assistant Professor of Pathology, Harvard Medical School

    Office phone: 617-632-4380
    Fax: 617-582-8761
    Email: ronny_drapkin@dfci.harvard.edu
    Website: The Drapkin Lab

    Preferred contact method: email
     
     

    Research Department

    Medical Oncology/Molecular and Cellular

    Area of Research

    Biology and Genetics of Ovarian Cancer


    Dana-Farber Cancer Institute
    450 Brookline Avenue
    JFB 215D
    Boston, MA 02215

    Biography

    Dr. Drapkin received his PhD in 1996 and his MD in 1998 from the University of Medicine and Dentistry of New Jersey, followed by postgraduate training in anatomic pathology at Brigham and Womens Hospital. He completed a research fellowship with Dr. David Livingston at Dana-Farber, where he developed a keen interest in the pathogenesis and genetics of womens cancers. He joined the Dana-Farber faculty in 2005.

    Recent Awards

    • Helene Harris Memorial Trust Traveling Fellowship, 2011
    • Mary Kay Foundation Research Award, 2010
    • Distinguished Alumnus Award, Rutgers Graduate School of Biomedical Sciences, 2008
    • Lynne Cohen Foundation for Ovarian Cancer Research, Best Research Prize, 2006
    • Dunkin Donuts Rising Stars Award, 2005

    Research

    Biology and Genetics of Ovarian Cancer

    Research in the Drapkin laboratory focuses on developing a comprehensive understanding of cancer pathogenesis, DNA repair mechanisms, and genomics of women’s cancers with a special focus on ovarian and breast carcinomas. The ultimate goal is to translate important principles discovered in the laboratory into clinical useful diagnostic and therapeutic tools.

    To accomplish these goals, the laboratory has developed a number of enabling platforms, including robust in vitro and in vivo tools which allow us to interrogate the role of any given genetic alteration in tumor development. These model systems also allow us to evaluate changes associate with chemotherapeutic response, and to identify companion diagnostics and biomarkers for early detection.

    These tools are deployed to study pathogenesis, genetics, and methods of early detection.

    Pathogenesis: While there are many types of ovarian malignancies, high-grade serous carcinoma (HGSC) is the most common, aggressive, and lethal form. Recent work from our group and others suggests that a significant proportion of HGSCs arise from the fallopian tube epithelium (FTE) rather than from the surface of the ovary as previously thought. This new concept for serous tumorigenesis has led us to develop a number of novel model systems, including the ex-vivo model of benign FTE, the in-vitro fallopian tube secretory cell transformation model, a genetically-engineered mouse model that targets the FTE, and a series of primary patient-derived tumor xenograft models that retain the phenotypic and genotypic properties of the original patient tumors. By integrating findings from genomic studies into these model systems, we aim to define key factors that can lead to new therapeutics and methods of early detection. 

    Cancer Genetics: The post-TCGA (The Cancer Genome Atlas) landscape for high-grade serous ovarian carcinoma is marked by surprisingly few recurrent somatic mutations. Instead, this disease exhibits a complex genomic terrain marked by copy number alterations that are so widespread that few other cancer types mirror its complexity. The challenge now is to elucidate the alterations that are key players in tumorigenesis, tumor viability and chemotherapy resistance. Although mutations in the BRCA genes account for less than 10% of all HGSCs, dysfunction in the BRCA network and homologous recombination appears to be more widespread. Intriguingly, the TCGA analysis found that BRCA mutation and Cyclin E (CCNE1) gain are largely mutually exclusive, yet both BRCA1/2 dysfunction and CCNE1 amplification lead to wide-spread genomic instability and tumor progression. PARP inhibition has been shown to be synthetically lethal with BRCA1, while CCNE1 amplification is associated with primary treatment failure and poor outcome. We are now deploying whole genome screens in our in vitro and in vivo platforms to investigate the role of CCNE1 in early tumor progression and to define the circuitry of these tumors that might reveal new avenues for therapeutic intervention. 

    Early Detection: There are currently no tools available for the early detection of ovarian cancer. Using a combination of FTE-derived ex-vivo models and highly refined mass spectrometry we are interrogating the secretome of malignant cells versus benign FTE cells. We have identified a number of candidate biomarkers, including HE4 and Elafin. Our prior work on HE4 showed that it was expressed and secreted as a glycoprotein by HGSCs. It was recently approved by the FDA for monitoring patients with HGSCs. Expression of Elafin is associated with poor overall survival and the protein exhibits mitogenic properties that likely underlie its association with poor outcome. Work in progress is aimed at defining the underlying mechanism of these effects.

    Select Publications

    • Levanon K, Ng V, Piao HY, Zhang Y, Chang MC, Roh MH, Kindelberger DW, Hirsch MS, Crum CP, Marto JA, Drapkin R (2010).  Primary ex vivo cultures of human fallopian tube epithelium as a model for serous ovarian carcinogenesis.  Oncogene 29: 1103-1113.
    • Clauss A, Ng V, Liu J, Piao HY, Russo M, Vena N, Sheng Q, Hirsch MS, Bonome T, Matulonis U, Ligon AH, Birrer MJ, Drapkin R (2010).  Overexpression of Elafin in ovarian carcinoma is driven by genomic gains and activation of the NF-kB pathway and is associated with poor overall survival.  Neoplasia 12: 161-172.
    • Cheung HW, Cowley GS, Weir BA, Boehm JS, Rusin S, Scott JA, East A, Ali LD, Lizotte PH, Wong TC, Jiang G, Hsiao J, Mermel CH, Getz G, Barretina J, Gopal S, Tamayo P, Gould J, Tsherniak A, Stransky N, Luo B, Ren Y, Drapkin R, Bhatia SN, Mesirov JP, Garraway LA, Meyerson M, Lander ES, Root DE, Hahn WC (2011).  Systematic investigation of genetic vulnerabilities across cancer cell lines reveals lineage-specific dependencies in ovarian cancer.  Proc Natl Acad Sci 108: 12372-7.
    • Karst AM, Levanon K, Duraisamy S, Liu JF, Hirsch MS, Hecht J, Drapkin R (2011).  Stathmin 1, a marker of PI3K pathway activation and regulator of microtubule dynamics, is expressed in early serous carcinomas.  Gyn Oncol 123: 5-12.
    • Karst AM, Levanon K, Drapkin R (2011).  Modeling high-grade serous ovarian carcinogenesis from the fallopian tube.  Proc Natl Acad Sci 108: 7547-7552.
    • Karst AM, Drapkin (2012).  Primary culture and immortalization of human fallopian tube secretory epithelial cells.  Nature Protocols 7: 1755-64.
    • Ren Y, Cheung HW, von Maltzhan G, Agrawal A, Cowley GS, Weir BA, Boehm JS, Tamayo P, Karst AM, Liu JF, Hirsch MS, Mesirov JP, Drapkin R, Root DE, Lo J, Fogal V, Ruoslahti E, Hahn WC, Bhatia SN (2012).  Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer oncogene ID4.  Sci Transl Med 4: 147ra112.
    • Verhaak RG, Tamayo P, Yang JY, Hubbard D, Zhang H, Creighton CJ, Fereday S, Lawrence M, Carter SL, Mermel CH, Kostic AD, Etemadmoghadam D, Saksena G, Cibulskis K, Duraisamy S, Levanon K, Sougnez C, Tsherniak A, Gomez S, Onofrio R, Gabriel S, Chin L, Zhang N, Spellman PT, Zhang Y, Akbani R, Hoadley KA, Kahn A, Kobel M, Huntsman D, Soslow RA, Defazio A, Birrer MJ, Gray JW, Weinstein JN, Bowtell DD, Drapkin R, Mesirov JP, Getz G, Levine DA, Meyerson M; Cancer Genome Atlas Research Network (2013).  Prognostically relevant gene signatures of high-grade serous ovarian carcinoma.  J Clin Invest 123: 517-25.
    • Levanon K, Sapoznik S, Bahar-Shany K, Brand H, Shapira-Frommer R, Korach J, Hirsch MS, Roh MH, Miron A, Liu JF, Vena N, Ligon AH, Fotheringham S, Bailey D, Flavin RJ, Birrer MJ, Drapkin RI (2013).  FOXO3a loss is a frequent early event in high-grade pelvic serous carcinogenesis.  Oncogene [Epub ahead of print].

    Trainees

    • Karst, Alison, PhD
    • Duraisamy, Sekhar, PhD
    • Elias, Kevin, MD
    • Novak, Marian, PhD
    • Emori, Megan, Graduate Student
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