• Leung, Peter C.K.

    Titles

    Investigator, BC Children's Hospital
    Associate Dean, Graduate & Postdoctoral Education, Faculty of Medicine, University of British Columbia
    Professor, Division of Research, Department of Obstetrics & Gynecology, University of British Columbia

    Degrees / Designations
    PhD
    Primary Area of Research
    Healthy Starts
    Secondary Area(s) of Research
    Phone
    604-875-2718
    Fax
    604-875-2717
    Lab Phone
    604-875-2361
    Assistant
    Roshni Nair
    Assistant Phone
    604-875-3108
    Mailing Address

    BC Children's Hospital
    Room C420
    4500 Oak Street
    Vancouver, BC  V6H 3N1

    Affiliate Websites
    Research Areas
    • Reproductive biology
    • Endocrinology
    Summary

    Gonadotropin-releasing hormone (GnRH) is a key regulator of mammalian reproduction. After its release from the hypothalamus, this decapeptide hormone is transported from the brain via the portal blood circulation to the anterior pituitary gland, where it stimulates the synthesis and release of the gonadotropins that play pivotal roles in the regulation of the gonads (i.e. ovary and testis). In addition, GnRH has been implicated as an autocrine regulator in several extra-pituitary tissues, including the ovary and placenta, but the specific functions are still unknown. Numerous synthetic analogs of GnRH are now being used in different areas of reproductive medicine, such as assisted reproduction. The long-term goal of my research program is to understand the multi-faceted role of GnRH in reproductive health and medicine.

    Current Projects

    Endocrine control of reproduction
    The aim of this project is to better understand the hormonal control of reproductive function by GnRH. Experiments are designed to test the hypothesis that, in addition to its well-known role in the regulation of pituitary hormone secretion, GnRH is also an autocrine regulator of ovarian hormone production. Further experiments are proposed to examine the regulation of the human GnRH receptor, at the level of gene transcription. It is expected that this research will lead to a better understanding on the cellular and molecular basis underlying the use of GnRH analogs in many different areas of reproductive medicine, such as fertility and sterility, control of ovulation and assisted reproductive technology.

    Function of GnRH in endometrium and placenta
    The establishment of a successful pregnancy is dependent on the coordinated development of the implanting embryo and the lining of the uterus (endometrium). To date, the regulatory factors involved in the development of a uterine environment that promotes embryonic implantation and/or the formation of functional placenta remain poorly characterized. In this project, the regulation of GnRH in endometrial and trophoblast cells undergoing differentiation in culture will be examined. A better 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 unexplained infertility.

    Normal and neoplastic ovarian surface epithelium -endocrine and hereditary influences
    The epithelial ovarian carcinomas, which comprise over 85% of human ovarian cancers, arise in the ovarian surface epithelium (OSE). The etiology and early events in the progression of these carcinomas are among the least understood of all major human malignancies because there are no appropriate animal models, and because methods to culture OSE have become available only recently. The purpose of this project is to define the molecular mechanisms which underlie the control of normal and neoplastic OSE cell growth, differentiation and expression of indicators of neoplastic progression, by GnRH and other key reproductive hormones. Also, the hormonal response of OSE isolated from overtly normal ovaries of women with and without family histories of ovarian cancer will be examined, in order to define the specific abnormalities in the OSE that lead to a high risk of developing ovarian cancer. The results of this research will be relevant to the development of more efficient chemotherapeutic methods for ovarian cancer treatment.

    Selected Publications

    Cheng CK, Hoo RLC, Chow BKC, Leung PCK (2003): Functional cooperation between multiple regulatory elements in the untranslated exon 1 stimulates the basal transcription of the human GnRH-II gene. Molecular Endocrinology (in press).

    Hoo, RLC, Ngan ESW, Leung PCK, Chow BKC (2003): Two Inr elements are important for mediating the activity of the prximal promoter of the human gonadotropin-releasing hormone receptor gene. Endocrinology 144:518-527.

    Chou CS, Tai CJ, MacCalman CD, Leung PCK (2003): Dose-dependent effects of gonadotropin-releasing hormone on matrix metalloproteinase (MMP)-2, MMP-9 and tissue specific inhibitor of metalloproteinases-1 messenger ribonucleic acid levels in human decidual stromal cells in vitro. J Clin Endocrin Metab 88:680-688.

    Khosravi S, Leung PCK (2003): Differential regulation of GnRH-I and GnRH-II mRNA by gonadal steroids in human granulosa luteal cells. J Clin Endocrin Metab 88:663-672.

    Chou CS, Zhu H, Shalev E, MacCalman CD, Leung PCK (2002): The effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on the urokinase-type plasminogen activator (UPA)/plasminogen activator inhibitor (PAI-I) system in human extravillous cytotrophoblasts in vitro. J Clin Endocrin Metab 87:5594-5603.

    Choi KC, Tai CJ, Tseng CR, Auersperg N, Leung PCK (2002): Adenosine triphosphate activates mitogen-activated protein kinase in pre-neoplastic and neoplastic ovarian surface epithelial cells. Biology of Reproduction 68:309-315.

    Cheng CK, Yeung CM, Chow BKC, Leung PCK (2002: Characterization of a new upstream of gonadotropin-releasing hormone receptor promoter in human ovarian granulosa-luteal cells. Molecular Endocrinology 16:1552-1562.

    Choi KC, Kang SK, Tai CJ, Auersperg N, Leung PCK (2002): Follicle-stimulating hormone activates mitogen-activated protein kinase in normal and neoplastic ovarian surface epithelial cells. J Clin Endocrin Metab 87:2245-2253.

    Cheng KW, Leung PCK (2002): Human chorionic gonadotropin-activated camp pathway regulates human placental gonadotropin-releasing hormone receptor gene transcription in choriocarcinoma JEG-3 cells. J Clin Endocrin Metabol 87:3291-3299.

    Lee PSN, Buchan AMJ, Hsueh AJW, Ho Yuen B, Leung PCK (2002): Intracellular calcium mobilization in response to the activation of human wild-type and chimeric gonadotropin receptors. Endocrinology 143:1732-1740.

    Kariminia A, Ivison SM, Leung VM, Sung S, Couto N, Rozmus J, Rolf N, Narendran A, Dunn SE, Reid GS, Schultz KRY-box- binding protein 1 contributes to IL- 7 mediated survival signaling in B- cell precursor acute lymphoblastic leukemia. Oncol Lett. 2017 Jan;13 PMID: 28123588 Impact Factor: 1.42.

    S. Evelyn Stewart, Yu-Pei Hu, Aldrich Leung, Elaine Chan, Dianne M. Hezel, Sraah Yao Lin, Laura Belschner, Casey Walsh, Daniel A. Geller, David L. Pauls. A Multisite Study of Family Functioning Impairment in Pediatric Obsessive-Compulsive Disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 2017 March 3, 56 (3): 241-249. PMID:28219490 

    Tian S1, Lin XH, Xiong YM, Liu ME, Yu TT, Lv M, Zhao W, Xu GF, Ding GL, Xu CM, Jin M, Feng C5, Wu YT, Tan YJ, Gao Q, Zhang J, Li C, Ren J, Jin LY, Chen B, Zhu H, Zhang XY, Chen SC, Liu XM, Liu Y, Zhang JY, Wang L, Zhang P, Chen XJ, Jin L, Chen X, Meng YC, Wu DD, Lin H, Yang Q, Zhou CL, Li XZ, Wang YY2, Xiang YQ, Liu ZW, Gao L, Chen LT, Pan HJ, Li R, Zhang FH8, Xing LF8, Zhu YM, Klausen C, Leung PC, Li JX, Sun F, Sheng JZ, Huang HF. Prevalence of Prediabetes Risk in Offspring Born to Mothers with Hyperandrogenism. Ebio Medicine. 2017 Jan 11 PMID: 28111236

    Wu HM, Huang HY, Schally AV, Chao A, Chou HH, Leung PC, Wang HS. Growth hormone-releasing hormone antagonist inhibits the invasiveness of human endometrial cancer cells by down-regulating twist and N-cadherin expression. Oncotarget. 2016 Dec 10 PMID: 28032599 

    Wu YT, Chang HM, Huang HF, Sheng JZ, Leung PC. Bone morphogenetic protein 2 regulates cell-cell communication by down-regulating connexin43 expression in luteinized human granulosa cells. Mol Hum Reprod. 2016 Dec 16 PMID: 2798693

    Liu PP, Chang HM, Cheng JC, Leung PC. Activin  A upregulates PTGS2 expression and increases PGE2 production in human granulosa-lutein cellsReproduction. 2016 Dec;152(6):655-664. PubMed PMID: 27624482.

     

    Grants

    CIHR Operating Grant - Project: "Regulation of human ovarian granulosa cell function by GDF9 and BMP15"

    Honours & Awards
    UBC Killam Research Award - 2009
    Honorary Professor of the Institute of Zoology, Chinese Academy of Sciences, Beijing - 2002-present
    Distinguished Scholar of the Michael Smith Foundation for Health Research - 2001-present
    Honorary Member of the Taiwan Society of Reproductive Medicine - 1996-present
    Consulting Professor of the Harbin Medical University, China - 1984-present
    Career Investigator of the BC Research Institute for Children's & Women's Health - 1988-2001
    Director of Ovarian Workshops, USA - 1994-2000
    Director of the Society for the Study of Reproduction, USA - 1995-1998
    President of the Canadian Fertility and Andrology Society - 1996-1997
    Medical Research Scientist Award - 1988-1993
    Research Group Members
    • Ki-Yon Kim, DVM, MSc - Gradate student
    • Se-Hyung Park, DVM, MSc - Graduate student
    • Beum-Soo An, DVM, MSc - Graduate student
    • Jung-Hye Choi, MSc - Graduate student
    • In-Sun Hong - Graduate student
    • Shuko Murakami, PhD - Postdoctoral fellow
    • Christian Klausen, PhD - Postdoctoral fellow
    • Dong Wook Park, PhD - Postdoctoral fellow
    • Haruka Aashina - Visiting graduate student
    • Dr. Chien-Lin Chen - Visiting scientist
    • Dr. Jong-Rak Choi - Visiting scientist