Photo of Patricia K. Donahoe, MD

Patricia K. Donahoe, MD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-1600
Fax: (617) 726-5057


pdonahoe@partners.org

Photo of Patricia K. Donahoe, MD

Massachusetts General Hospital
Phone: (617) 724-1600
Fax: (617) 726-5057


pdonahoe@partners.org

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Patricia K. Donahoe, MD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Marshall K. Bartlett Distinguished Professor of Surgery, Surgery, Harvard Medical School
  • Director, Pediatric Surgical Research Laboratories, Pediatric Surgical Services, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our laboratory studies the molecular mechanisms by which TGFB family proteins suppress growth, focusing on Mullerian Inhibiting Substance (MIS) as a model. After purifying MIS protein and cloning its gene, we cloned the genes for its type I and type II receptors and a number of other receptors of this transmembrane serine/threonine kinase family, and used homologous recombination to uncover their early embryonic function using human ovarian and breast carcinomas as targets for MIS, the laboratory discovered that MIS produced G1 arrest and apoptosis by inducing p16 in ovarian cancer, and by inducing NFKB and regulating the specific IEX-1S isoform in breast cancer cell lines. Preclinical trials of MIS are underway in preparation for phase I clinical trials in human ovarian cancer patients.

We also study the molecular mechanisms of sex differentiation and of foregut development to correct congenital anomalies of the trachea and esophagus. As she and her colleagues search for gene defects causing congenital anomalies, they hope to design in utero pharmacologic therapies to reduce the severity of the abnormalities at birth.

Publications

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  • 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
  • Park SH, Chung YJ, Song JY, Kim SI, Pépin D, MacLaughlin DT, Donahoe PK, Kim JH. Müllerian inhibiting substance inhibits an ovarian cancer cell line via β-catenin interacting protein deregulation of the Wnt signal pathway. Int J Oncol 2017; 50:1022-1028. 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
  • Beck TN, Korobeynikov VA, Kudinov AE, Georgopoulos R, Solanki NR, Andrews-Hoke M, Kistner TM, Pépin D, Donahoe PK, Nicolas E, Einarson MB, Zhou Y, Boumber Y, Proia DA, Serebriiskii IG, Golemis EA. Anti-Müllerian Hormone Signaling Regulates Epithelial Plasticity and Chemoresistance in Lung Cancer. Cell Rep 2016; 16:657-71. 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
  • Chung YJ, Kim HJ, Park SH, Yoon JH, Kim MR, Nam SW, MacLaughlin DT, Donahoe PK, Kim JH. Transcriptome analysis reveals that Müllerian inhibiting substance regulates signaling pathways that contribute to endometrial carcinogenesis. Int J Oncol 2015; 46:2039-46. PubMed
  • Park JH, Tanaka Y, Arango NA, Zhang L, Benedict LA, Roh MI, Donahoe PK, Teixeira JM. Induction of WNT inhibitory factor 1 expression by Müllerian inhibiting substance/antiMullerian hormone in the Müllerian duct mesenchyme is linked to Müllerian duct regression. Dev Biol 2014; 386:227-36. PubMed
  • Namkung J, Song JY, Jo HH, Kim MR, Lew YO, Donahoe PK, MacLaughlin DT, Kim JH. Mullerian inhibiting substance induces apoptosis of human endometrial stromal cells in endometriosis. J Clin Endocrinol Metab 2012; 97:3224-30. PubMed
  • Chang HL, Pieretti-Vanmarcke R, Nicolaou F, Li X, Wei X, MacLaughlin DT, Donahoe PK. Mullerian inhibiting substance inhibits invasion and migration of epithelial cancer cell lines. Gynecol Oncol 2010; 120:128-34. PubMed
  • Wei X, Dombkowski D, Meirelles K, Pieretti-Vanmarcke R, Szotek PP, Chang HL, Preffer FI, Mueller PR, Teixeira J, Maclaughlin DT, Donahoe PK. Mullerian inhibiting substance preferentially inhibits stem/progenitors in human ovarian cancer cell lines compared with chemotherapeutics. Proc Natl Acad Sci U S A 2010; 107:18874-9. PubMed
  • Papakostas TD, Pieretti-Vanmarcke R, Nicolaou F, Thanos A, Trichonas G, Koufomichali X, Anago K, Donahoe PK, Teixeira J, MacLaughlin DT, Vavvas D. Development of an efficiently cleaved, bioactive, highly pure FLAG-tagged recombinant human Mullerian Inhibiting Substance. Protein Expr Purif 2010; 70:32-8. PubMed
  • MacLaughlin DT, Donahoe PK. Müllerian inhibiting substance/anti-Müllerian hormone: a potential therapeutic agent for human ovarian and other cancers. Future Oncol 2010; 6:391-405. PubMed
  • Chang HL, Senaratne TN, Zhang L, Szotek PP, Stewart E, Dombkowski D, Preffer F, Donahoe PK, Teixeira J. Uterine leiomyomas exhibit fewer stem/progenitor cell characteristics when compared with corresponding normal myometrium. Reprod Sci 2010; 17:158-67. PubMed
  • Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco MM, Wijendran V, Shioda T, Sgroi D, Donahoe PK, Maheswaran S. HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci U S A 2010; 107:1100-5. PubMed
  • Fujino A,Arango NA,Zhan Y,Manganaro TF,Li X,MacLaughlin DT,Donahoe PK. Cell migration and activated PI3K/AKT-directed elongation in the developing rat Mullerian duct. Dev Biol 2008; 325:351-62. PubMed
  • Lage K,Hansen NT,Karlberg EO,Eklund AC,Roque FS,Donahoe PK,Szallasi Z,Jensen TS,Brunak S. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes. Proc Natl Acad Sci U S A 2008; 105:20870-5. PubMed
  • Szotek PP,Chang HL,Brennand K,Fujino A,Pieretti-Vanmarcke R,Lo Celso C,Dombkowski D,Preffer F,Cohen KS,Teixeira J,Donahoe PK. Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics. Proc Natl Acad Sci U S A 2008; 105:12469-73. PubMed
  • Kantarci S,Ragge NK,Thomas NS,Robinson DO,Noonan KM,Russell MK,Donnai D,Raymond FL,Walsh CA,Donahoe PK,Pober BR. Donnai-Barrow syndrome (DBS/FOAR) in a child with a homozygous LRP2 mutation due to complete chromosome 2 paternal isodisomy. Am J Med Genet A 2008; 146A:1842-7. PubMed
  • Renlund N, Pieretti-Vanmarcke R, O'Neill FH, Zhang L, Donahoe PK, Teixeira J. c-Jun N-terminal kinase inhibitor II (SP600125) activates Mullerian inhibiting substance type II receptor-mediated signal transduction. Endocrinology 2007; 149:108-15. PubMed
  • Kantarci S, Donahoe PK. Congenital diaphragmatic hernia (CDH) etiology as revealed by pathway genetics. Am J Med Genet C Semin Med Genet 2007; 145:217-26. PubMed
  • Szotek PP, Chang HL, Zhang L, Preffer F, Dombkowski D, Donahoe PK, Teixeira J. Adult mouse myometrial label-retaining cells divide in response to gonadotropin stimulation. Stem Cells 2007; 25:1317-25. PubMed
  • Gupta V, Yeo G, Kawakubo H, Rangnekar V, Ramaswamy P, Hayashida T, MacLaughlin DT, Donahoe PK, Maheswaran S. Mullerian-inhibiting substance induces Gro-beta expression in breast cancer cells through a nuclear factor-kappaB-dependent and Smad1-dependent mechanism. Cancer Res 2007; 67:2747-56. PubMed
  • Pieretti-Vanmarcke R, Donahoe PK, Pearsall LA, Dinulescu DM, Connolly DC, Halpern EF, Seiden MV, MacLaughlin DT. Mullerian Inhibiting Substance enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer. Proc Natl Acad Sci U S A 2006; 103:17426-31. PubMed
  • Arango NA, Huang TT, Fujino A, Pieretti-Vanmarcke R, Donahoe PK. Expression analysis and evolutionary conservation of the mouse germ cell-specific D6Mm5e gene. Dev Dyn 2006; 235:2613-9. PubMed
  • Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, Maclaughlin DT, Donahoe PK. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A 2006; 103:11154-9. PubMed
  • Zhan Y, Fujino A, MacLaughlin DT, Manganaro TF, Szotek PP, Arango NA, Teixeira J, Donahoe PK. Müllerian inhibiting substance regulates its receptor/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Müllerian duct regression. Development 2006; 133:2359-69. PubMed
  • Donahoe PK. Genomic approaches to surgical diseases: 21st annual Samuel Jason Mixter lecture. Arch Surg 2006; 141:409-13. PubMed
  • Pieretti-Vanmarcke R, Donahoe PK, Szotek P, Manganaro T, Lorenzen MK, Lorenzen J, Connolly DC, Halpern EF, MacLaughlin DT. Recombinant human Mullerian inhibiting substance inhibits long-term growth of MIS type II receptor-directed transgenic mouse ovarian cancers in vivo. Clin Cancer Res 2006; 12:1593-8. PubMed
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DF/HCC members that share similar concepts* with Patricia K. Donahoe, MD but have yet to coauthor a publication with this researcher.

* Concepts are MeSH terms, automatically derived from member publications

Similar Members