Translational Oncology Scientist,
London Regional Cancer Program
Associate Professor, Department of Obstetrics & Gynecology
Cross Appointments: Department of Oncology &
Department of Anatomy & Cell Biology
Ovarian cancer is a devastating malignancy since in many cases women are first diagnosed after the disease has already spread, or metastasized. Even after aggressive surgery and combination cytotoxic chemotherapy, very often this relentless disease returns quickly with evolved chemotherapy-resistance. Therefore, the overarching theme of the Shepherd lab, within the Translational Ovarian Cancer Research Program (TOCRP) is to elucidate the molecular and cellular mechanisms involved in ovarian cancer metastasis and test new therapeutic strategies to target and alleviate late-stage disease and chemo-resistance.
The TOCRP represents fundamental and translational research activities co-led by scientists Drs. Shepherd and Gabriel DiMattia (Depts. of Oncology & Biochemistry), and in close collaboration with gynaecologic oncology surgeons and other members of the Gynaecologic Oncology Multidisciplinary Disease Site Team at the London Regional Cancer Program. Together, the TOCRP team has made significant discoveries through the novel development and use of ovarian cancer patient ascites-derived cell lines representing disease diversity and their application of an in vitro three-dimensional spheroid culture model of metastasis and tumour biology. The continued objective of the TOCRP is to ultimately apply new research discoveries to impact the lives of ovarian cancer patients with improved therapies to prolong disease-free survival and improve overall quality-of-life.
1. Bioenergetic stress signalling mediated by Liver kinase B1 and its downstream kinase substrates in ovarian cancer spheroids and metastasis.
2. Therapeutic targeting of autophagy as an integral survival mechanism in ovarian cancer metastasis.
3. Regulatory mechanisms underlying epithelial-mesenchymal transition in the pathogenesis of ovarian cancer spheroids and metastasis.
4. Impact of interpatient and intratumoral heterogeneity in ovarian cancer on efficacy of oncolytic virus infection and cell killing.
Go to www.theshepherdlab.com for more details.
Samah Rafehi, Yudith Ramos Valdes, Jessica Tong, Monique Bertrand, Jacob McGee, Michel Préfontaine, Akira Sugimoto, Gabriel E. DiMattia, Trevor G. Shepherd (2016) Transforming growth factor-beta signalling regulates epithelial-mesenchymal transition in ascites-derived epithelial ovarian cancer spheroids. Endocrine-related Cancer 23: 147-59. [Pubmed]
Rohann J.M. Correa, Yudith R. Valdes, Trevor G. Shepherd and Gabriel E. DiMattia (2015) Beclin-1 expression is retained in high-grade serous ovarian cancer yet is not essential for autophagy induction in vitro. Journal of Ovarian Research 8:52. [Pubmed]
Jessica G. Tong, Yudith R. Valdes, John W. Barrett, John C. Bell, David Stojdl, Grant McFadden, J. Andrea McCart, Gabriel E. DiMattia, Trevor G. Shepherd (2015) Evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis. Molecular Therapy – Oncolytics 2: 15013 [Pubmed]
Teresa M. Peart, Yudith R. Valdes, Rohann J.M. Correa, Elena Fazio, Monique Bertrand, Jacob McGee, Michel Prefontaine, Akira Sugimoto, Gabriel E. DiMattia, Trevor G. Shepherd (2015) Intact LKB1 activity is required for survival of dormant ovarian cancer spheroids. Oncotarget 6: 22424-38. [Pubmed]
Rohann J.M. Correa, Yudith R. Valdes, Teresa M. Peart, Monique Bertrand, Jacob McGee, Michel Prefontaine, Akira Sugimoto, Gabriel E. DiMattia, and Trevor G. Shepherd (2014) Combination of AKT inhibition with autophagy blockade effectively reduces ascites-derived ovarian cancer cell viability. Carcinogenesis 35:1951-61. [Pubmed]
Shoudong Li, Jessica Tong, Masmudur M. Rahman, Trevor G. Shepherd, Grant McFadden (2012) Oncolytic virotherapy of ovarian cancer. Oncolytic Virotherapy 1:1-21. [Pubmed]
Rohann J. M. Correa, Monica Komar, Jessica Tong, Milani Sivapragasam, Masmudur M. Rahman, Grant McFadden, Gabriel E. DiMattia, Trevor G. Shepherd (2012) Myxoma virus-mediated oncolysis of ascites-derived human ovarian cancer cells and spheroids is impacted by differential AKT activity. Gynecol Oncol 125: 441-450. [Pubmed]
Teresa M. Peart, Rohann J.M. Correa, Yudith R. Valdes, Gabriel E. DiMattia and Trevor G. Shepherd (2012) BMP signalling controls the malignant potential of ascites-derived human epithelial ovarian cancer spheroids via AKT kinase activation. Clin Exp Metastasis 29: 293-313. [Pubmed]
Rohann J.M. Correa, Teresa M. Peart, Yudith R. Valdes, Gabriel E. DiMattia and Trevor G. Shepherd (2011) Modulation of AKT activity is associated with reversible dormancy in ascites-derived epithelial ovarian cancer spheroids. Carcinogenesis 33: 49-58. [Pubmed]