Explore These Labs


The Pediatric Surgical Research Laboratories were established in 1973 under the directorship of Patricia K. Donahoe, MD, Chief Emeritus of the Pediatric Surgical Services.

The Pediatric Surgical Research Laboratories focus on areas of Developmental Biology which hold promise for clinical application. Patricia Donahoe, MD, 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 duct. 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-up rhMIS production in mammalian cells with an industrial partner, for use in preclinical and clinical trials against human tumors of Mullerian Duct origin. The first target will be ovarian cancers, followed by endometrial and cervical cancers. The laboratory has recently detected a stem cell enriched population in both the normal surface epithelium of the ovary, the site of origin of most human ovarian cancers, and in ovarian cancer primary and established cell lines where the stem cell enriched population was shown to be remarkably responsive to MIS but paradoxically stimulated by Doxorubin and other chemotherapeutic agents. Studies are underway to target these cancer stem cells selectively. Stem cell markers and functional studies will be used to select patients for inclusion in clinical trials using recombinant human MIS.

The laboratory also focuses on using array comparative genomic hybridization (aCGH) to elucidate disruptive single nucleotide polymorphisms and micro-deletions and duplications using whole exomic sequencing and array comparative genomic hybridization (CGH) to select candidate genes contributing to Congenital Diaphragmatic Hernia (CDH). Dr. Donahoe and our surgical colleagues at Massachusetts General Hospital and at Children’s Hospital of Boston along with collaborators from this country and abroad have enrolled over 400 patients in the study of the genetics of CDH and have established cell lines from patients, parents, and siblings. Mauro Longoni, MD, Meaghan Russell, PhD and Frances High, MD, PhD are using 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, Ph.D. to integrate this data. This entire program is coordinated between the Mass General for Children, Childrens Hospital, Brigham and Women's Hospital, and the Broad Institute. Transcriptome arrays have been done in collaboration with the Jackson Laboratory, and developmental studies and analyses have been done in collaboration with the University of Rochester. All of these studies are supported by NICHD. Using the study of CDH as a template, it is the aim of the laboratory to apply the tools and algorithms devised herein to study the genetics of a number of other congenital abnormalities that affect the infants and children for whom we care in the Pediatric Surgical Department at the Mass General for Children, since here and in other children’s hospitals, children with birth defects fill one third of the hospital beds in the US.

Ongoing Research

Pépin Laboratory

The Pépin Laboratory in the Department of Surgery at Massachusetts General Hospital is exploring the basic biology of how hormones regulate female reproductive development with the goal of translating curiosity-driven research to the clinic to benefit women’s health. In addition to sex steroids, the ovary produces a number of other less understood reproductive hormones such as Mullerian inhibiting substance (MIS or AMH) and follistatin (FST), which are necessary for female health. While we continue to apply novel technologies to pursue all aspects of reproduction, contraception, oncofertility, reproductive aging, and oncology, our ultimate goal is to develop therapeutics capable of modulating the MIS and FST pathways and evaluate them in our fertility and ovarian cancer models to develop new treatments that address unmet clinical needs in women’s health and beyond.

Learn more about the Pépin Laboratory

Congenital Diaphragmatic Hernia (CDH) Study

For over 10 years, a dedicated team of clinicians at Mass General for Children and Children’s Hospital Boston, scientists, and collaborators world-wide have been working together to better understand the genetic mechanisms underlying congenital diaphragmatic hernia (CDH) and abnormally small lungs (pulmonary hypoplasia). The cornerstones of this project are the individualized assessment of CDH patients, state-of-the-art genetic screening, and integration of data from animal models (i.e. mice, chicks and flies) to identify new genes and molecular pathways necessary for diaphragm and lung development. We hope to harness the benefit of genetic analyses/testing to find potential treatment strategies that may prevent or alleviate CDH and pulmonary hypoplasia in the future.

We are particularly interested in finding a non-invasive pharmacologic approach to enhance maturation of hypoplastic lungs in utero. It is our estimation that even a small improvement of lung function prenatally, would have a profound effect on improving survival and reducing long term complications.

The CDH study, which is funded by the National Institutes of Health, has recently expanded to include several additional research centers, which have world-renowned expertise in analyses of whole-genomic variation, mutant mouse model development and embryonic characterization, and bioinformatic assessment of complex anomalies. It is with great hope that our strategy will serve as a model for studies of other genetically complex congenital malformations.

Participate in the CDH Study