Trevor Shepherd obtained his undergraduate degree from The University of Western Ontario Honours Genetics Program in 1995 before going on to perform graduate studies with Dr. John Hassell at McMaster University. For his PhD, he studied the function of the PEA3 subfamily of Ets transcription factors in breast cancer using transgenic mouse models in collaboration with Dr. Bill Muller. After completing his PhD degree in 2002, he switched to studying ovarian cancer with Dr. Mark Nachtigal at Dalhousie University where he initiated his work with patient-derived primary cell culture techniques. He was recruited back to Southwestern Ontario in 2007 as an Assistant Professor in Ob/Gyn, Oncology and Anatomy & Cell Biology at Western University and a Translational Oncology Scientist at the London Regional Cancer Program. His work over the last several years has focused on developing an in vitro model of ovarian cancer metastasis to investigate altered pathobiology and how these malignant changes can be targeted therapeutically. His work has been supported by the US DOD, CRS, and CCSRI, and he currently holds a CIHR grant to investigate stress metabolism signalling in ovarian cancer metastasis and tumour dormancy.
Professional and Academic Experience
The focus of my research program has been to understand the mechanisms controlling ovarian cancer metastasis. Ovarian cancer spreads in a unique way compared with most other solid tumours, in that metastatic cells directly disseminate throughout the peritoneal cavity, oftentimes in the form of multicellular aggregates or spheroids within malignant ascites. As such, the majority of my translational research involves the direct culture and analysis of ovarian cancer cells and spheroids collected from ascites fluid of ovarian cancer patients [Shepherd et al. (2006) Nat Protocols]. Using these clinically-derived samples, I have identified a number of signalling pathways and pathobiological features of ascites-derived ovarian cancer cells and three-dimensional multicellular clusters called spheroids. Spheroids afford resident cancer cells the ability to evade chemotherapy, survive in suspension, and enhance their ability to form secondary tumours in the abdomen. Thus, understanding the mechanisms controlling spheroid formation and the cellular biology within these structures is critical to developing novel and effective strategies to treat recurrent late-stage, chemotherapy-resistant disease in patients. Importantly, I have also contributed to the development of novel histotype-specific cell lines generated from ovarian cancer ascites. This evolved from the biorepository that I helped to establish in the TOCRP.
Dept. of Obstetrics & Gynaecology Dept. of Oncology Dept. of Anatomy & Cell Biology Schulich School of Medicine & Dentistry Western University
|Senior Oncology Scientist||London Regional Cancer Program London Health Sciences Centre||July 2016-|
|Translational Oncology Scientist||London Regional Cancer Program London Health Sciences Centre||2007-present|
|Associate Scientist||Lawson Health Research Institute||2007-present|
Additional Research Activities
Transforming growth factor-beta and bone morphogenetic protein signalling: I was the first to discover that ovarian cancer cells possess intact bone morphogenetic protein (BMP) signalling that functions to promote cell spreading via cell-substratum adhesion [Shepherd and Nachtigal (2003) Endocrinology] as well as to upregulate the ID1 and ID3 proto-oncogene overexpression observed in ovarian tumours [Shepherd et al. (2008) Gene]. As an independent investigator, I have extended this work to show that BMP signalling was downregulated during spheroid formation to promote cell aggregation, and that ectopic expression of a constitutively-active BMP type I receptor negatively impacts spheroid formation [Peart et al. (2012) Clin Exp Metastasis].
Tumour spheroids as a model system for discovery research: An essential component of my laboratory’s research was the development and use of an in vitro experimentally-tractable model system that mimics ovarian cancer metastasis. I have developed a rapid, easy and reproducible cell culture system to establish spheroids in liquid suspension, where they can be visualized microscopically, treated with pharmacologic agents or viral vectors, and subsequently transferred to adherent culture as a model of secondary tumour formation.
Oncolytic viruses: A secondary objective for our spheroid culture system of ovarian cancer metastasis, particularly with ascites-derived clinical specimens, is to directly test the efficacy of novel therapeutics.