Leung, Peter CK Titles - UBC Department of Obstetrics ...

Name:Titles:Degrees / Designations:Primary Area of Research:Secondary Area(s) of Research:Email:Leung, Peter C.K.Professor, Department of Obstetrics & Gynaecology,University of British ColumbiaProgram DirectorReproductive and Developmental SciencesPhDReproductive HealthPhone: 604­875­2718Fax: 604­875­2717Laboratory Phone: 604­875­2361Assistant:peleung@interchange.ubc.caRoshni NairAssistant Phone: 604­875­3108Mailing Address:Room 2H30 ­ 4500 Oak St.Vancouver, BCV6H 3N1Research Areas· Reproductive biology· EndocrinologySummaryGonadotropin­releasing hormone (GnRH) is a key regulator of mammalian reproduction. After itsrelease from the hypothalamus, this decapeptide hormone is transported from the brain via theportal blood circulation to the anterior pituitary gland, where it stimulates the synthesis and releaseof the gonadotropins that play pivotal roles in the regulation of the gonads (i.e. ovary and testis). Inaddition, GnRH has been implicated as an autocrine regulator in several extra­pituitary tissues,including the ovary and placenta, but the specific functions are still unknown. Numerous syntheticanalogs of GnRH are now being used in different areas of reproductive medicine, such as assistedreproduction. The long­term goal of my research program is to understand the multi­faceted role ofGnRH in reproductive health and medicine.Current ProjectsEndocrine control of reproductionThe aim of this project is to better understand the hormonal control of reproductive function byGnRH. Experiments are designed to test the hypothesis that, in addition to its well­known role in theregulation of pituitary hormone secretion, GnRH is also an autocrine regulator of ovarian hormoneproduction. Further experiments are proposed to examine the regulation of the human GnRHreceptor, at the level of gene transcription. It is expected that this research will lead to a betterunderstanding on the cellular and molecular basis underlying the use of GnRH analogs in manydifferent areas of reproductive medicine, such as fertility and sterility, control of ovulation andassisted reproductive technology.Function of GnRH in endometrium and placentaThe establishment of a successful pregnancy is dependent on the coordinated development of theimplanting embryo and the lining of the uterus (endometrium). To date, the regulatory factorsinvolved in the development of a uterine environment that promotes embryonic implantation and/orthe formation of functional placenta remain poorly characterized. In this project, the regulation ofGnRH in endometrial and trophoblast cells undergoing differentiation in culture will be examined. Abetter understanding of the role of GnRH and related hormones in implantation and placentation is

likely to reduce the number of couples assigned the frustrating and costly diagnosis of unexplainedinfertility.Normal and neoplastic ovarian surface epithelium ­endocrine and hereditary influencesThe epithelial ovarian carcinomas, which comprise over 85% of human ovarian cancers, arise in theovarian surface epithelium (OSE). The etiology and early events in the progression of thesecarcinomas are among the least understood of all major human malignancies because there are noappropriate animal models, and because methods to culture OSE have become available onlyrecently. The purpose of this project is to define the molecular mechanisms which underlie thecontrol of normal and neoplastic OSE cell growth, differentiation and expression of indicators ofneoplastic progression, by GnRH and other key reproductive hormones. Also, the hormonalresponse of OSE isolated from overtly normal ovaries of women with and without family histories ofovarian cancer will be examined, in order to define the specific abnormalities in the OSE that lead toa high risk of developing ovarian cancer. The results of this research will be relevant to thedevelopment of more efficient chemotherapeutic methods for ovarian cancer treatment.Selected PublicationsKim KY, Choi KC, Auersperg N, Leung PCK. “Mechanism of gonadotropin­releasing hormone(GnRH)I and II­induced cell growth inhibition in ovarian cancer cells: role of the GnRH­I receptorand protein kinase C pathway. Endocrine­related cancer 13:211­220 (2006).Choi JH, Choi KC, Auersperg N, Leung PCK. “Gonadotropins activate proteolysis and increaseinvasion via protein kinase A and phosphatidyl­inositol­3­kinase in human epithelial ovarian cancercells”. Cancer Research 66:3912­3920 (2006).Choi KC, Jeung EB, Leung PCK. “Impact of environmental endocrine disruption in femalereproductive system for women’s health”. Current Medicinal Chemistry­Immunology. Endocrineand Metabolic Agents 6:3­13 (2006).Choi JH, Choi KC, Auersperg N, Leung PCK. “Differential regulation of two forms of gonadotropinreleasinghormone messenger ribonucleic acid by gonadotropins in human immortalized ovariansurface epithelium and ovarian cancer”. Endocrine Related Cancer 13:641­651 (2006).An BS, Selva DM, Hammond GL, Rivero­Muller A, Rahman N, Leung PCK. “Steroid receptorcoactivator­3 is required for progesterone receptor trans­activation of target genes in response togonadotropin­releasing hormone treatment of pituitary cells”. Journal of Biological Chemistry281:20817­20824(2006).Choi JH, Ota T, Gilks CB, Auersperg N, Leung PCK. “Immuno Localization ofgonadotropin­releasing hormone (GnRH)­I, GnRH­I I and type­1 GnRH receptor during folliculardevelopment in the normal human ovary”. J Clin Endocrin Metab 91:4562­4570 (2006).Cheung LWT, Leung PCK, Wong AST. “Gonadotropin­releasing hormone promotes ovarian cancercell invasiveness through c­Jun N­terminal kinase­mediated activation of matrix metalloproteinase­2and ­9. Cancer Research 66:10902­10910 (2006).Leung PCK, Choi JH. “Endocrine Signaling in ovarian Cancer”, Human Reproduction Update 13:143­162 (2007).Wong AST, Leung PCK. “Role of endocrine and growth factors on the ovarian surface epithelium”.Journal of Obstetrics and Gynecology Research 33:3­16 (2007).Choi JH, Wong AST, Huang, Leung PCK. “Gonadotropins and ovarian cancer”, Endocrine Reviews28:440­461 (2007).Honours & Awards

Honorary Professor of the Institute of Zoology, Chinese Academy of Sciences, Beijing ­ 2002­presentDistinguished Scholar of the Michael Smith Foundation for Health Research ­ 2001­2006Honorary Member of the Taiwan Society of Reproductive Medicine ­ 1996­presentInstitute Advisory Board Member of the CIHR Institute of Gender and Health – 2004­presentCareer Investigator of the BC Research Institute for Children's & Women's Health ­ 1988­2001Director of Ovarian Workshops, USA ­ 1994­2000Director of the Society for the Study of Reproduction, USA ­ 1995­1998President of the Canadian Fertility and Andrology Society ­ 1996­1997Medical Research Scientist Award ­ 1988­1993Research Group MembersSe­Hyung Park, DVM, MSc ­ Graduate studentIn­Sun Hong ­ Graduate studentFengtao Shi – Graduate studentSong Ling Poon – Graduate studentJunling Chen – Graduate studentMan Tat Lau – Graduate studentWai Kin So – Graduate studentJung­Chien Chen­ Graduate studentDr. Qing Huang – Postdoctoral Fellow