Patricia K. Donahoe

Patricia K. Donahoe, MD directs the Pediatric Surgical Research Laboratories at the Massachusetts General Hospital where her research in Developmental Biology and Genetics focuses on areas of which hold promise for clinical application for birth defects, contraception, and ovarian cancer.

The Pediatric Surgical Research Laboratories were established in 1973 under the directorship of Patricia K. Donahoe, MD, now Chief Emerita of the Pediatric Surgical Services at the Massachusetts General Hospital and Marshall K. Bartlett Professor of Surgery at the Harvard Medical School.  Dr. Donahoe and her colleagues have purified recombinant human Mullerian Inhibiting Substance (rhMIS) which directs normal male phenotypic development in the fetus by causing regression of the female reproductive ducts.  This fetal regressor, MIS, is now being developed as a novel treatment for cancers arising in the female reproductive tracts of adults; work is underway to scale recombinant human MIS production for use in preclinical and clinical trials against such tumors.  The laboratory has recently detected a stem cell enriched population in both the normal surface epithelium of the ovary, a site of origin of human ovarian cancers, and in ovarian cancer primary cell lines where stem cell enriched populations were shown to be remarkably responsive to MIS but paradoxically stimulated by Doxorubin and other chemotherapeutic agents presently used to treat these cancers.  Studies are underway to target these cancer stem cells selectively.   Recent studies by David Pepin, PhD also aim to develop MIS as a contraceptive agent and as a germ cell protectant during chemotherapy.

The laboratory also focuses on using array comparative genomic hybridization (cCGH) and whole exomic sequencing to elucidate disruptive single nucleotide polymorphisms and micro-deletions and duplications to uncover promising candidate genes contributing to Congenital Diaphragmatic Hernia (CDH).  Dr. Donahoe and her surgical colleagues at Massachusetts General Hospital and at Children’s Hospital of Boston along with collaborators from this country and abroad have enrolled over 500 patients in an NICHD supported program project to study of the genetics of CDH and have established cell lines from patients, parents, and siblings.  Mauro Longoni, MD and Frances High, MD, PhD have used next generation whole exomic sequencing, array CGH, single-nucleotide polymorphism (SNP) arrays, and embryonic diaphragm expression arrays followed by novel bioinformatics algorithms designed by Kasper Lage, PhD to integrate and prioritize this data.  Using the study of CDH as a template, it is the aim of the laboratory to apply the tools and algorithms devised to study the genetics of a number of other congenital abnormalities that affect the infants and children cared for in the Pediatric Surgical Department at the MassGeneral Hospital for Children, since here and in other children’s hospitals in the US, children with birth defects fill one third of the hospital beds.  The greatest legacy of the laboratory and Dr. Donahoe’s greatest joy has been the laboratory’s record training over a hundred Research Fellows and graduate students who have gone on to lead laboratories and services around the globe.