Description of Research Expertise:
The Drapkin laboratory focuses on developing a comprehensive understanding of the genetic, molecular and physiological factors that drive the development of cancer, with a special focus on gynecologic malignancies. Recent work from our group and others has implicated the fallopian tube (FT) secretory cell as the likely cell-of-origin for a majority of high-grade serous ovarian carcinomas. This new concept of ovarian tumorigenesis has been a paradigm shift in the field and the Drapkin lab has been at the forefront in developing novel experimental platforms that address the role of the FT epithelium and its susceptibility to neoplastic transformation. These platforms include genetically engineered mouse (GEM) models, fallopian tube-derived cell lines, and patient-derived tumor xenografts. The lab is currently focused on utilizing these models to interrogate how genetic and epigenetic alterations influence lineage dependencies, genomic instability, DNA repair, replicative stress, and metabolism. The goal is to define selective vulnerabilities that can guide novel therapeutic approaches and biomarker development.
KEYWORDS: Ovarian cancer, Genomics/Epigenomics of precursor lesions, Cyclin E, Replication Stress, BRCA1/2, DNA Repair, Protein complexes, Biomarkers, Animal models.
Rotation projects are open to students in each of the areas the lab focuses on. Please see Ronny Drapkin to discuss potential rotation projects.
Marilyn Mitchell, Lab Manager
Kai Doberstein, PhD, Postdoctoral Researcher
Jagmohan Hooda, PhD, Postdoctoral Researcher
Sarah Stuckelberger, MD, Postdoctoral Researcher
Daniele Moreira, Pharm PhD, Postdoctoral Researcher
Paul Kroeger Jr, PhD, Postdoctoral Researcher
Yasuko Kinose, MD, PhD, Visiting Assistant Professor
Sho Sato, MD, Postdoctoral Researcher
Yi Feng, Graduate Student
Andrea Klein, Undergraduate Student
Cristina Arruza, Undergraduate Student
Melissa Song, Undergraduate Student
Labidi-Galy SI, Papp E, Hallberg D, Niknafs N, Adleff V, Noe M, Bhattacharya R, Novak M, Jones S, Phallen J, Hruban CA, Hirsch MS, Lin DI, Schwartz L, Maire CL, Tille JC, Bowden M, Ayhan A, Wood LD, Scharpf RB, Kurman R, Wang TL, Shih IM, Karchin R, Drapkin R*: High grade serous ovarian carcinomas originate in the fallopian tube. Nature Communications 8 (1): 1093,2017.
Liu JF, Palakurthi S, Zeng Q, Zhou S, Ivanova E, Huang W, Zervantonakis IK, Selfors LM, Shen Y, Pritchard CC, Zheng M, Adleff V, Papp E, Piao H, Novak M, Fotheringham S, Wulf G, English J, Kirschmeier PT, Velculescu VE, Paweletz CP, Mills GB, Livingston DM, Brugge JS, Matulonis UA: Establishment of patient-derived tumor xenograft models of epithelial ovarian cancer for pre-clinical evaluation of novel therapeutics. Clin Can Res 23 (5): 1263-1273,2017.
Kroeger PT Jr: Pathogenesis and heterogeneity of ovarian cancer. Curr Opin Obstet Gynecol 29 (1): 26-34,2017.
Au-Yeung G, Lang F, Azar WJ, Mitchell C, Jarman KE, Lackovic K, Aziz D, Cullinane C, Pearson RB, Mileshkin L, Rischin D, Karst AM, Drapkin R, Etemadmoghadam D: Selective targeting of Cyclin E1 amplified high grade serous ovarian cancer by cyclin-dependent kinase 2 and AKT inhibition. Clin Can Res 23 (7): 1862-1874,2017.
Elias KM, Emori MM, Westerling T, Long H, Budina-Kolomets A, Li F, MacDuffie E, Davis MR, Holman A, Lawney B, Freedman ML, Quackenbush J, Brown M: Epigenetic remodeling regulates transcriptional changes between ovarian cancer and benign precursors. JCI Insight 1 (13): e87988,2016.
Elias KM, Emori MM, Papp E, MacDuffie E, Konecny GE, Velculescu VE: Beyond genomics: critical evaluation of cell line utility for ovarian cancer research. Gynecol Oncol 139 (1): 97-103,2015.
Davidowitz RA, Selfors LM, Iwanicki MP, Karst AM, Piao HY, Ince TA, Dering J, Konecny GE, Matulonis U, Mills GB, Slamon DJ, Drapkin R*: Mesenchymal gene program-expressing ovarian cancer spheroids exhibit enhanced mesothelial clearance. J Clin Invest 124(6):2611-25 : 2014.
Karst AM, Jones PM, Vena N, Ligon AH, Liu JF, Hirsch MS, Etemadmoghadam D, Bowtell DD: Cyclin E1 deregulation occurs early in secretory cell transformation to promote formation of fallopian tube-derived high-grade serous ovarian cancers. Cancer Res 74 (4): 1141-52,2014.
Perets R, Muto KW, Bijron JG, Poole BB, Chin KT, Kwak S, Chen JYH, Karst AM, Setlur SR, Hirsch MS, Crum CP, Dinulescu DM: Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models. *Highlighted in Nature Reviews Cancer, Cancer Discovery, and Cancer Research. Cancer Cell 24: 751-65 : 2013.
Karst AM, Levanon K: Modeling high-grade serous ovarian carcinogenesis from the fallopian tube. *Highlighted in Nature Reviews Cancer and JNCI Proc Natl Acad Sci 108: 7547-7552 : 2011.
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