Angela Tonary, Ph.D.
Expression, regulation and function of the Kit tyrosine kinase receptor and its ligand in human epithelial ovarian cancer.
I was Barb’s second Ph.D. student. I officially started my Ph.D. with Barb in May 1994, and my studies looked at the expression, regulation, and function of the Kit tyrosine kinase and its ligand, stem cell factor, in epithelial ovarian cancer. In November 1999, I joined Adherex Technologies, Inc. as a Research Scientist and I developed cell lines and cell-based assays for the screening of drug candidates, targeting the cadherin class of proteins, for the Cancer and Transdermal Programs. I wrote and defended my Ph.D. thesis during my first year with Adherex. In January 2003, I joined Dr. John P. Pezacki’s lab at the Steacie Institute for Molecular Sciences (SIMS), one of the institutes of the National Research Council Canada, and over the next four years I worked in the areas of liver tissue engineering, activity-based protein profiling of host-HCV interactions, and developing novel intracellular imaging methods (the latter with colleagues at Harvard University). Since April 2007, I have been working as a Scientific Evaluator at Health Canada, in the Natural Health Products Section of the Marketed Health Products Directorate. Our Section investigates post-market safety issues associated with natural health products (NHPs). I can be reached at Angela_Tonary@hc-sc.gc.ca or at 613-957-3571 .
Behnam Azadi, M.Sc. Candidate
Investigation of synergistic effect of soy milk components and fenretinide on ovarian cancer cells.
The use of herbal or natural products is growing significantly worldwide. These products can interact with synthetic drugs, but the particular interactions between natural anti-cancer drugs derived from soy milk and fenretinide against ovarian cancer have not yet been tested. Fenretinide is a synthetic retinoid derived from vitamin A that is currently undergoing testing as a chemopreventive and chemotherapeutic agent and is therefore a promising agent for ovarian cancer therapy in the near future. Evidence from recent studies demonstrate that bioactive compounds from soy milk in physiologic concentrations can kill cancer cells. My M.Sc. thesis project involved understanding the interaction between natural drugs from soy milk and fenretinide. The goal of my project was to optimize the combination of natural and synthetic drug to cause the strongest effects on the cancer cells. Identification of any synergistic effects may reduce the dose of fenretinide needed to achieve maximum effect and consequently minimize its side effects. In my research project I used in vitro cell culture models and evaluated the cytotoxicity of drugs on ovarian cancer cell lines. I previously obtained a B.Sc. degree in biomedical sciences from Iran Azad University. I am currently working as a Research Technician at McGill University.
Catia Céméus, M.Sc., Research Technician
Identifying and characterizing potential adult stem cells on the surface of the ovary.
Catia joined the ovarian cancer group to work with Dr Ethier on a project investigating the roles of activin and inhibin in ovarian cancer. Catia received a B.Sc diploma from the Université du Québec à Montréal and a M.Sc diploma in Pharmaceutical Sciences from the University of Montreal. She has expertise in animal handling, cell culture and molecular biology techniques, and is currently working as a Research Technician with Dr. Jim Dimitroulakos at the Centre for Cancer Therapeutics.
Colleen Crane, Medical Laboratory Technologist
My priority in the Vanderhyden lab was to maintain the tissues and corresponding records for the Ottawa Ovarian Tumour Bank. I was a major contributor to the translational research component of the Gynecologic Oncology Group clinical trial of Gleevec in ovarian cancer patients, performing and analyzing all related immunostaining. My training as a laboratory technologist was put to good use for all histology set up and cell morphology analyses, participating in nearly all projects in the group, especially the development and characterization of mouse models. I am now working full-time in Cytology in the Department of Pathology and Laboratory Medicine at The Ottawa Hospital.
David Pepin, Ph.D. Candidate
Chromatin remodeling in the context of folliculogenesis and kallikreins as therapeutic targets in ovarian cancer.
My PhD research focused on the ATP-dependent chromatin remodeling proteins of the ISWI family, SNF2H and SNF2L. Using a mutant mouse model we characterized the reproductive phenotype of SNF2L-deficient ovaries. More precisely, we focused on SNF2L-dependent coordination of gene expression in differentiating granulosa cells during follicle maturation. Additionally, we tested the use of recombinant kallikrein 10 (KLK10) as a therapeutic in xenograft models of ovarian cancer. While a PhD student, I was supported by an Ontario Graduate Scholarship in Science and Technology. I am currently a post-doctoral research fellow at Harvard Medical School and Massachusetts General Hospital in the lab of Dr. Patricia K Donahoe. My research focuses on the pre-clinical evaluation of recombinant MIS in the treatment of ovarian cancer. I am currently an Ann Schreiber Program of Excellence award recipient.
Elizabeth Pitre, M.Sc.
Identifying the role of the developmental HOX genes in the differentiation of epithelial ovarian cancer.
I joined the Vanderhyden lab in 2007 after completing an Honours B.Sc. in Bio-Medical Science at the University of Guelph to study the role of HOX genes in the progression of epithelial ovarian cancer. HOX genes play a critical role in the patterning and development of the female reproductive tract, and they are also abnormally expressed in the histologically distinct subtypes of epithelial ovarian cancer. My research project involved using in vitro culture models and a mouse model of ovarian cancer to determine the effects of HOX gene overexpression on the differentiation of this malignancy into its various subtypes. My graduate work was supported by an Ontario Graduate Scholarship and a CIHR-Canada Graduate Scholarship Master's Award. Since May 2010, I have been working as a Clinical Research Assistant for the Ontario Tumour Bank at The Ottawa Hospital. The Ontario Tumour Bank is a province-wide biorepository and data bank focused on collection of a diverse selection of tumour-related human biospecimens for use by academic and industry cancer researchers.
Female fertility is dependant upon adequate follicle and oocyte growth within the ovary and on proper embryo development following ovulation and fertilization. These events require profound morphological and biochemical changes including the constant modulation of gene expression to ensure that every cell is correctly equipped to fulfill its function at the appropriate time. The control of gene expression occurs at multiple level but we are particularly interested in the epigenetic event triggering changes in DNA conformation thereby allowing or preventing the transcriptional machinery to access the genes. The ATP-dependant chromatin remodeling protein, Snf2h and Snf2l, are part of larger complex that are thought to be important for this process. Using transgenic mice model deficient for Snf2h and/or Snf2l, we worked to identify the phenotype associated with the loss of functions, identify their target genes and determine their role during normal follicle and oocyte growth and during preimplantation embryo development. I am currently working as a Research Associate with Agriculture and Agri-Food Canada in Edmonton, AB. My current work is focused on understanding the impact of maternal nutrition during gestation on fetal programming in beef cattle.
Fu Jian Yan, M.Sc.
Regulation of KitL expression and its effects on oocyte growth
The cellular and molecular events that promote oocyte growth and developmental competence must be determined in order to improve the success of assisted reproductive technologies such as In Vitro Fertilization (IVF). As a postdoc in the Vanderhyden lab, I investigated the importance of oocyte-somatic cell interactions in mediating oocyte growth and maturation in vitro. My work was supported by a Canadian Institutes of Health Research Strategic Initiative Fellowship, funded by a STIRRHS bursary. My current position is a postdoc with Dr. Hamish Fraser at the MRC Human Reproductive Sciences in Edinburgh.
Jean-François Ethier, Ph.D.
Roles of activin and inhibin in ovarian cancer
Improper regulation of factors controlling normal ovarian functions may lead to ovarian carcinomas. Several studies have suggested that such factors may include activin and inhibin. It has been shown that activin stimulates the proliferation of several ovarian cancer cell lines, while inhibin has been described as a tumor suppressor with gonadal specificity in the mouse. The occurrence of ovarian cancer is considerably higher in post-menopausal women. Interestingly, menopausal women experience a decline in circulating inhibin levels and an increase in activin circulating levels. The goals of our study were: 1) to determine whether inhibin has a protective role against ovarian cancer. 2) to determine whether the deregulation of activin expression or its signaling pathway has a role in the development and progression of ovarian carcinomas. My work was supported by a Gynecological Cancer Research Award that was sponsored by the Mitchell Family Fund, the National Ovarian Cancer Association, and Cancer Care Ontario. I am currently an Assessment Officer at Health Canada's Bureau of Metabolism, Oncology and Reproductive Sciences, Oncology Division.
Jin-Yi Jiang, Ph.D., Post-Doctoral Fellow
While a postdoc in the Vanderhyden lab, I was interested in the cellular and molecular mechanisms in the regulation of ovarian follicular development and atresia, and oocyte growth and maturation. My studies focused on 1) the importance of Kit ligand (KitL), a granulosa cell-derived factor, in the promotion of oocyte growth, and 2) the regulation of KitL expression by intraovarian factors (i.e. TGF-beta).
Katherine Clark-Knowles, Ph.D.
The role of tumour suppressor genes in the transformation of the ovarian surface epithelium.
My Ph.D. project focused on the role of tumour suppressors in the transformation of the mouse ovarian surface epithelium (OSE). Our lab has several lines of transgenic mice that are conditional knockouts for various tumour suppressor genes (BRCA1, p53 and Rb), either alone or in combination, that are relevant to ovarian cancer development and progression. These genes can be conditionally inactivated based on the Cre-LoxP system. I studied the effects of inactivation of these genes on the ovarian surface epithelium either in vivo, via intrabursal administration of adenoviral Cre recombinase, or in vitro using primary cultures of mouse ovarian surface epithelial (OSE) cells. The elucidation of the early genetic events that take place in the OSE that lead either to the development of ovarian cancer or to a preneoplastic lesion in the ovary, will aid in the identification of possible strategies for early detection and for the development of genetically relevant mouse models of this disease. I am currently a Research Associate with Dr. M. McBurney at the Ottawa Hospital Research Institute, continuing work on mouse models of human cancers.
Kerri Courville, Transgenic Technician
As the only staff member of the Ottawa Regional Cancer Centre/University of Ottawa Transgenic Mouse Facility, Kerri was solely responsible for the generation of all transgenic and knock-out mice for the Vanderhyden lab as well as for external collaborators. Kerri maintained the transgenic mice in a pathogen-free barrier facility, where she did all their breeding, weaning, identification and genotyping by PCR. Kerri was also a part of the Vanderhyden lab’s Mouse Models of Ovarian Cancer group, which aims to generate mouse models of ovarian cancer using a variety of strategies, including tissue-specific expression of oncogenic signals, the Cre-lox system for conditional expression, and intra-bursal injection of adenoviral vectors. Kerri was a member of the Vanderhyden lab from December 2001 to September 2007.
Laura Laviolette, Ph.D. Candidate
Examining the role of the reproductive hormones on ovarian cancer initiation and progression.
My PhD research project utilized a transgenic mouse model of ovarian cancer developed and characterized in the Vanderhyden lab to examine the role of the female reproductive hormones (LH, FSH, estrogen and progesterone) on ovarian cancer initiation and progression. While a PhD student, I was supported by an Ontario Women?s Health Council/CIHR - Institute of Gender and Health Doctoral Research Award. I am currently a post-doctoral research fellow at Harvard Medical School and Massachusetts General Hospital in the lab of Dr. Othon Iliopoulos. My research focuses on determining the function of a tumour suppressor protein, folliculin (FLCN). Mutations in the FLCN gene give rise to Birt-Hogg-Dube syndrome, a dominantly inherited genetic disease with clinical symptoms that include fibrofolliculomas, lung cysts and kidney cancer.
Lesley Dunfield, Ph.D.
The role of Gleevec in enhancing chemosensitivity of ovarian cancer cells.
While working in the Vanderhyden lab as a postdoc, I was supported by a Terry Fox Foundation Fellowship through the National Cancer Institute of Canada. The development of chemoresistance is a major impediment to the treatment of many cancer types, including ovarian cancer. Novel treatment strategies are necessary to increase ovarian cancer chemosensitivity, which may lead to improved patient outcome. While in the Vanderhyden lab, I investigated the use of Gleevec co-treatment to enhance cisplatin chemosensitivity in ovarian cancer cell lines. I currently work as a research officer for the Canadian Agency for Drugs and Technologies in Health.
Lisa Gamwell, Ph.D.
Identifying and characterizing potential adult stem cells on the surface of the ovary.
I obtained a Bachelor of Science, Honours degree in Biochemistry and Physiology at the University of Ottawa, and recently completed my Ph.D. studying epithelial cells found on the surface of the ovary. Almost 90% of ovarian tumours are thought to arise from the ovarian surface epithelium (OSE), a layer of cells that covers the surface of the ovary and is ruptured during ovulation. I published the first article that identified a marker to enrich stem cells from the OSE and have performed additional work to characterize their role in ovulatory wound healing and in the early stages of ovarian cancer. While I was a PhD student, I was supported by a Canadian Institutes of Health Research (CIHR) Canadian Graduate Student Master's Award and a scholarship from the CIHR Training Program in Reproduction, Early Development, and the Impact on Health. I am now working as an analyst at a biotech company in the Ottawa area.
Rita Shamoon, M.Sc. Candidate
Kit ligand (KitL) is a granulosa cell-derived factor essential for normal ovarian folliculogenesis. Mutations at its locus lead to sterility in female mice because of arrests in the early stages of follicular development. Research within our lab has revealed that FSH, an extraovarian factor important in the control of mammalian follicle development through a cAMP-mediated pathway, appears to have a regulatory affect on follicular KL expression in a dose-dependent manner. Additionally, evidence indicates that two intra-ovarian factors, GDF-9 and BMP-15, are not only obligatory for proper folliculogenesis, but have opposite actions on KitL expression, with GDF-9 being inhibitory and BMP-15 acting as a stimulatory factor. As a graduate student in the Vanderhyden lab, it was my interest to study the mechanisms by which FSH, GDF-9 and BMP-15 exert control over KitL expression. During this time, I was funded by an NSERC scholarship. I am currently in medical school at McMaster University.
Tanya Shaw, Ph.D.
The role of KIT and PDGF-R receptor signalling in ovarian cancer cells
My Ph.D. research project addressed the role of KIT and PDGF-R receptor tyrosine kinase signalling in ovarian cancer cells. I also characterized a panel of ovarian cancer cell lines based on the types of tumours they form in mice. These models proved useful not only for our in vivo pre-clinical evaluation of Gleevec, but also for the evaluation of other novel therapeutics for ovarian cancer in collaborative studies with biopharmaceutical start-up companies. During my graduate studies, I was supported by The Betty Irene West CIHR Doctoral Research Award. While working with Barb, I became interested in the epidemiological link between ovulatory wounds and ovarian cancer (and chronic wounds/inflammation and cancer at other anatomical sites). To pursue this interest, I initiated a Marie Curie Post-Doctoral Fellowship with Paul Martin (University of Bristol) ? a leading researcher in the skin wound healing field. Initially, I focused on how wound-associated inflammation contributes to fibrosis and scarring. With Ryoichi Mori, we disrupted one aspect of inflammation, osteopontin expression, which excitingly improved the rate and quality of repair (J Exp Med. 2008 Jan 21;205(1):43-51). Next, funded by NSERC and Cancer Research UK, Paul and I investigated how the vast number of genes induced in wound-edge epithelium may be regulated and coordinated. We discovered that gene expression in healing wounds is regulated ?epigenetically?, by transient changes in chemical modifications to DNA and chromatin (EMBO Rep. 2009 Aug;10(8):881-6).
I am now a lecturer at St. George's, University of London, and our research focuses on the cellular and molecular mechanisms of wound healing in skin and ovary. We are particularly interested in how the tissue repair process may go wrong, which in the skin may result in pathological scars such as keloids, or in the ovary may contribute to ovarian cancer.
Investigating the combined effect of Brca1 and estrogen on ovarian tumour initiation.
Women with germline mutations that inactivate their Brca1 gene are at an increased risk of developing breast and ovarian cancer, but it is not clear why Brca1 inactivation causes cancer predisposition in such a tissue-specific manner. Additionally, Brca1 loss alone does not cause tumour formation and therefore other molecular changes are required for ovarian tumour initiation. Evidence suggests that loss of Brca1 function increases the expression of aromatase, the enzyme that produces estrogen. My hypothesis was therefore that elevated estradiol secretion from Brca1-deficient cells in the ovary could promote the proliferation and transformation of estrogen-responsive cell types in the ovary and I tested this idea using both mouse and cell culture models. Since completing my master's degree in the Vanderhyden Lab, I have been working as an Aquatic Science Technician with Fisheries and Oceans Canada in my hometown of Dartmouth, Nova Scotia. I perform genetic analysis on marine organisms for a wide variety of projects, including a captive rearing program for endangered Atlantic Salmon.
Valerie Bourada, M.Sc.
Testing the therapeutic efficacy of an oncolytic virus on a mouse model of ovarian cancer.
My project was designed to address the potential efficacy of the oncolytic virus, vesicular stomatitis virus (VSV), in a mouse model of ovarian cancer. VSV is an oncolytic virus that has been shown to be effective in vitro and in vivo in xenograft and syngeneic mouse models of cancer. Many mouse models of cancer that have been treated with VSV have shown an increase in the survival and/or a decrease in the tumour burden of the mice. Our lab has generated a line of transgenic mice (tgMISIIRTAg ) in which 100% of the females develop bilateral ovarian tumours. This project was supported by an Ontario Graduate Scholarship in Science and Technology. I am currently a clinical research assistant at the Ottawa Hospital Research Institute?s oncology clinical research program.
Vanderhyden lab at the Canadian Conference on Ovarian Cancer Research, 2004