Photo of David Pepin,  PhD

David Pepin, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 838-3810


dpepin@partners.org

David Pepin, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Surgery, Harvard Medical School
  • Assistant Molecular Biologist, Surgery, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

My laboratory is focused on developing translational approaches to the study of ovarian cancer, particularly for the treatment and prevention of chemoresistant recurrences. We have previously shown that the use of gene therapy vectors based on adeno-associated virus serotype 9 (AAV9) can be effective in delivering biologics for long term treatment of chemoresistant recurrences using patient-derived xenograft models developed in the laboratory. Those PDX models mimic the current standard of care by considering surgical debulking and chemotherapy, and allow us to infer the variability of patient responsiveness by personalizing to individual patient's tumors. One of the biologics we are evaluating, Mullerian Inhibiting Substance (MIS), was shown to be effective in inhibiting ovarian cancer growth. Additionally, we have shown that co-treatment with MIS during chemotherapy suppresses ovarian folliculogenesis, thus also preserving fertility during treatment. These applications are being pursued pre-clinically.

Publications

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  • Chauvin M, Garambois V, Choblet S, Colombo PE, Chentouf M, Gros L, De Brauwere DP, Duonor-Cerutti M, Dumas K, Robert B, Jarlier M, Martineau P, Navarro-Teulon I, Pépin D, Chardès T, Pèlegrin A. Anti-Müllerian hormone concentration regulates activin receptor-like kinase-2/3 expression levels with opposing effects on ovarian cancer cell survival. Int J Oncol 2021. PubMed
  • Meinsohn MC, Saatcioglu HD, Wei L, Li Y, Horn H, Chauvin M, Kano M, Nguyen NMP, Nagykery N, Kashiwagi A, Samore WR, Wang D, Oliva E, Gao G, Morris ME, Donahoe PK, Pépin D. Single-cell sequencing reveals suppressive transcriptional programs regulated by MIS/AMH in neonatal ovaries. Proc Natl Acad Sci U S A 2021. PubMed
  • Tanimoto R, Sekii K, Morohaku K, Li J, Pépin D, Obata Y. Blocking estrogen-induced AMH expression is crucial for normal follicle formation. Development 2021. PubMed
  • Alkailani M, Palidwor G, Poulin A, Mohan R, Pepin D, Vanderhyden B, Gibbings D. A genome-wide strategy to identify causes and consequences of retrotransposon expression finds activation by BRCA1 in ovarian cancer. NAR Cancer 2021; 3:zcaa040. PubMed
  • Iyer S, Zhang S, Yucel S, Horn H, Smith SG, Reinhardt F, Hoefsmit E, Assatova B, Casado J, Meinsohn MC, Barrasa MI, Bell GW, Pérez-Villatoro F, Huhtinen K, Hynninen J, Oikkonen J, Galhenage PM, Pathania S, Hammond PT, Neel BG, Farkkila A, Pépin D, Weinberg RA. Genetically Defined Syngeneic Mouse Models of Ovarian Cancer as Tools for the Discovery of Combination Immunotherapy. 2021; 11:384-407. PubMed
  • Chauvin M, Garambois V, Colombo PE, Chentouf M, Gros L, Brouillet JP, Robert B, Jarlier M, Dumas K, Martineau P, Navarro-Teulon I, Pépin D, Chardès T, Pèlegrin A. Anti-Müllerian hormone (AMH) autocrine signaling promotes survival and proliferation of ovarian cancer cells. Sci Rep 2021; 11:2231. PubMed
  • Meinsohn MC, Hughes CHK, Estienne A, Saatcioglu HD, Pépin D, Duggavathi R, Murphy BD. A role for orphan nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) in primordial follicle activation. Sci Rep 2021; 11:1079. PubMed
  • Hart KN, Pépin D, Czepnik M, Donahoe PK, Thompson TB. Mutational Analysis of the Putative Anti-Müllerian Hormone (AMH) Binding Interface on its Type II Receptor, AMHR2. Endocrinology 2020. PubMed
  • Pépin D, Sabatini ME, Donahoe PK. Müllerian inhibiting substance/anti-Müllerian hormone as a fertility preservation agent. Curr Opin Endocrinol Diabetes Obes 2018; 25:399-405. PubMed
  • Hsu JY, James KE, Bormann CL, Donahoe PK, Pépin D, Sabatini ME. Mullerian-inhibiting substance/anti-Mullerian hormone as a predictor of preterm birth in polycystic ovary syndrome. J Clin Endocrinol Metab 2018. PubMed
  • Qi R, Wang Y, Bruno PM, Xiao H, Yingjie Y, Li T, Lauffer S, Wei W, Chen Q, Kang X, Song H, Yang X, Huang X, Detappe A, Matulonis U, Pepin D, Hemann MT, Birrer MJ, Ghoroghchian PP. Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer. Nat Commun 2017; 8:2166. PubMed
  • Kano M, Sosulski AE, Zhang L, Saatcioglu HD, Wang D, Nagykery N, Sabatini ME, Gao G, Donahoe PK, Pépin D. AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy. Proc Natl Acad Sci U S A 2017. PubMed
  • Sosulski A, Horn H, Zhang L, Coletti C, Vathipadiekal V, Castro CM, Birrer MJ, Nagano O, Saya H, Lage K, Donahoe PK, Pépin D. CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis. PLoS ONE 2016; 11:e0156595. PubMed
  • Pépin D, Sosulski A, Zhang L, Wang D, Vathipadiekal V, Hendren K, Coletti CM, Yu A, Castro CM, Birrer MJ, Gao G, Donahoe PK. AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer. Proc Natl Acad Sci U S A 2015; 112:E4418-27. PubMed
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