Translational Ovarian Cancer Research Program

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Welcome to the Shepherd Laboratory

Trevor G. Shepherd, PhD

Translational Oncology Scientist
Cancer Research Laboratories
London Regional Cancer Program

Assistant Professor
Departments of Obstetrics & Gynaecology, Oncology, and Anatomy & Cell Biology
Schulich School of Medicine & Dentistry
The University of Western Ontario

 

Exciting research projects currently available for Graduate students, Residents, and Honours students

I began on my path towards becoming a scientist by obtaining an undergraduate degree from the Honours Genetics program at the University of Western Ontario in 1995. Subsequently, I went on to graduate school in the Department of Medical Sciences at McMaster University and trained in the field of the molecular and cellular biology of breast cancer by studying transgenic and knockout mouse models of the disease. After successfully completing my PhD studies in 2002, I went to Dalhousie University in the Department of Pharmacology to initiate a new research direction into the poorly-understood yet devastating cancer in women, ovarian cancer. Supported by the NCIC with a Terry Fox Foundation Post PhD Fellowship, I developed techniques to isolate and culture normal human ovarian surface epithelial cells and ovarian cancer cells derived from patient ascites. With these cell cultures I was the first to identify and characterize BMP signalling and ID target gene regulation in ovarian cancer. I received additional technical training from laboratories at the Ottawa Regional Cancer Centre and the Massachusetts Institute of Technology to develop new mouse models of ovarian cancer. Taken together, these technologies involving the direct analysis of primary cells and tissues from patients and generation of accurate animal models for ovarian cancer will form the foundation for the Translational Ovarian Cancer Research Program at the London Health Sciences Centre.

Current Research Endeavours:

Translational Ovarian Cancer Research Program Ovarian cancer is the most lethal of the gynaecological cancers, yet over the last decade very little progress has been made to improve the overall survival of women with this disease. To try to buck this current trend, we at the LRCP are using an integrated, multidisciplinary team approach to quickly develop focused, clinically-relevant research endeavours.

Id genes in ovarian cancer The Inhibitors of DNA-binding (ID) genes encode negative-regulatory helix-loop-helix transcription factors. Id proteins typically act to block cell differentiation, and if overexpressed in cancer cells may help to promote tumorigenesis. In fact, ID1 and ID3 genes are overexpressed in epithelial ovarian cancer cells compared to normal ovarian surface epithelial cells. Thus, a major research focus of my laboratory is to uncover the functional implications of Id1 and Id3 expression in ovarian cancer cells.

Mouse models of ovarian cancer Great strides have been made in our understanding of initiation and progression of specific cancers through the development of accurate mouse models of the human disease. Up until very recently, however, there have not been any transgenic or knockout mice that heritably develop ovarian cancer. In close collaboration with Dr. Gabriel DiMattia, we are rapidly developing multiple novel strains of transgenic mice to better understand the initiating genetic events of epithelial ovarian cancer.

BMP signalling in ovarian cancer Bone morphogenetic protein (BMP) signalling is critically implicated very early in embryonic development to control the fate of cells and tissues. There is growing evidence that BMP signalling may be involved in several human cancers. We have demonstrated that epithelial ovarian cancer cells possess an intact autocrine BMP4 signalling pathway which influences the metastatic phenotype.

Modeling ovarian cancer metastasis The majority of ovarian cancer patients are first diagnosed with the disease when it has already spread from the primary site, or metastasized. Ovarian cancer is quite unique among the different types of carcinomas in that it very rarely leads to blood-borne metastasis; rather, ovarian cancer cells likely utilize alternative mechanisms to disseminate directly throughout the peritoneal cavity. Since most post-surgical treatment stratagies are to target and kill metastatic ovarian cancer cells hidden within the abdominal cavity, my laboratory is developing a cell culture and xenograft model system to dissect the underlying mechanisms controlling ovarian cancer metastasis.

Recent favourite papers Szotek PP et al (2008) Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics. Proc Natl Acad Sci USA Link

Woo MMM et al (2008) Serous borderline ovarian tumors in long-term culture: phenotypic and genotypic distinction from invasive ovarian carcinomas. Int J Gynecol Cancer Link

Jarboe E et al (2007) Serous carcinogenesis in the fallopian tube: a descriptive classification. Int J Gynecol Pathol 27: 1-9 Link

©2008 Trevor G. Shepherd PhD