Dr. William Gibb BSc Hons (Glas), Ph.D. (Aber)
Obstetrics and Gynecology,
Cellular and Molecular Medicine
University of Ottawa
Department of Physiology
University of Toronto
Biography is coming.
Preterm labor is a major problem in Obstetrics and its incidence has not been reduced in the past 20years. Studies in our laboratory are intended to define the molecular mechanisms occurring in labor at term and preterm and will hopefully lead to better methods to regulate preterm (and term labor). Prostaglandins are intimately involved in parturition and the regulation of prostaglandin synthesis , metabolism and action is the focus of our studies.
Regulation of PGHS-2 and PGDH expression in Human Pregnancy
On-going studies are designed to define the mechanism of glucocorticoid regulation of PGHS-2 expression, (the major enzyme involved in PG formation in pregnancy) and PGDH the major enzyme involved in the regulation of PG degradation. The role of glucocorticoid and progesterone receptors together with their co-activators and co-repressors in the regulation of PGHS-2 and PGDH in the human fetal membranes is being examined.
Regulation of Prostaglandin Production and Action in Pregnancy and Parturition
(With J.R.G. Challis (PI), and S. J. Lye, Department of Physiology, University of Toronto, D.Rurak and C. MacCalman, Department of Obstetrics and Gynecology, University of British Columbia.)
We have recently proposed a new model for the regulation of parturition in the sheep, whereby fetal glucocorticoids increase expression of PGHS-2 in the fetal placenta resulting in increased PGE2 production which stimulates expression of the P450C17 enzyme enabling progesterone to be converted to estrogen. The estrogen formed is then responsible for the increased production of PGF2a that occurs in the maternal tissues. On-going in vivo and in vitro studies are examining this model.
Role of Drug Resistance Proteins in Pregnancy
(With Dr S. G. Matthews, Department of Physiology, University of Toronto)
A group of transporters in the ATP binding cassette (ABC) superfamily have recently been found in the placenta including the multidrug resistant gene product 1 (Mdr-1) also known as P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). These proteins are potentially capable of protecting the fetus from a large number of drugs and toxins. Mdr-1/P-gp is also involved in the extrusion of various steroids including certain glucocorticoids and may therefore play an important role in regulating fetal access of glucocorticoids. Studies in human placenta and the mouse are being carried out to define the expression and regulation of Mdr-1/P-gp and BCRP. We have recently shown the there is a marked decrease in the expression of placental Mdr-/P-gp in the human and mouse placenta with advancing gestation which may be regulated by the decrease in progesterone levels seen in the latter species.
Canadian Institutes for Health Research (CIHR) Mechanism of Steroids in Parturition $380,000 (2005-2009); CIHR Multidrug Resistance in Pregnancy $385,000 (2002-2005), $637,975 (2005-2010), Co-PI with Dr Steve Matthews, University of Toronto; CIHR Regulation of Prostaglandin Synthesis, Metabolism and Action in Pregnancy and Parturition $775,000 (2004-2009) Co- investigator, PI Dr John Challis, University of Toronto.
Publications (past 5 years)
- Whittle WL, Gibb W, Challis JRG. The characterization of human amnion epithelial and mesenchymal cells; the cellular expression, activity and glucocorticoid regulation of prostaglandin output. Placenta. 21:394-401 (2000)
- Gyomorey S, Lye SJ, Gibb W and Challis JRG. Expression of prostaglandin receptors and PGHS-2 in ovine intrauterine tissues with the natural onset of labor. Biol. Reprod. 62:797-805 (2000).
- Gibb W, Sun M, Gyomorey S, Lye SJ, and Challis JRG. Localization of prostaglandin synthase type-1 (PGHS-1) mRNA and prostaglandin synthase type-2 (PGHS-2) mRNA in ovine myometrium and endometrium throughout gestation. J Endocrinol. 165:51-58 (2000)
- Gyomorey S, Gupta S, Lye SJ, Gibb W, Labrie F and Challis JRG. Temporal expression of PGHS-2 and P450C17 in ovine placentomes with the natural onset of labor. Placenta. 21:478-486 (2000)
- Challis JRG, Matthews SG, Gibb W, Lye SJ. Endocrine and Paracrine Regulation of Birth at Term and Preterm. Endoc Rev. 21:514-550 (2000)
- Whittle WL, Holloway AC, Lye SJ, Gibb W, Challis JRG. Prostaglandin Production at the Onset of Ovine Parturition is Regulated by both Estrogen-Independent and Estrogen-Dependent Pathways. Endocrinology. 141(10):3783-91 (2000).
- Whittle WL, Patel FA, Alfaidy N, Holloway AC, Fraser M, Gyomorey S, Lye SJ, Gibb W, Challis JRG. Glucocorticoid regulation of human and ovine parturition: The relationship between fetal hypothalamic-pituitary-adrenal axis activation and intrauterine prostaglandin production. Biol Reprod. 64:1019-1032 (2001)
- Yan X, Xiao CW, Sun M, Tsang BK and Gibb W. Nuclear Factor Kappa B (NFkB) Activation and Regulation of Cyclooxygenase Type-2 (COX-2) Expression in Human Amnion Mesenchymal Cells by IL-1b. Biol Reprod. 66:1667-1671 (2002)
- Martin RL, Whittle WL, Holloway AC, Gyomorey S, Gibb W, Lye S and Challis JRG. Ontogeny and Regulation of Ovine Placental Prostaglandin E2 Synthase. Biol Reprod. 67:868-873 (2002)
- Yan X, Sun M, and Gibb W. Localization of Nuclear Factor-kB (NFkB) and Inhibitory Factor-B (IkB) in Human Fetal Membranes and Decidua at Term and Preterm Delivery. Placenta. 23:288-293 (2002)
- Gibb W, Challis JRG. Mechanisms of term and preterm labor. J Obstet Gynecol Can. 24:874-883 (2002)
- Giannoulias D, Holloway A, Sun M, Gibb W, Lye SJ and Challis JRG. Expression of Prostaglandin I (2) Synthase, but not Prostaglandin E Synthase, Changes in Myometrium of Women at Term Pregnancy. J Clin Endocrinol Metab. 87 (11):5274-5282 (2002)
- Gupta S, Alfaidy N, Holloway AC, Whittle W, Gibb W, Challis JRG. Effects of Cortisol and Oestradiol on 11b-Hydroxysteroid Dehydrogenase – Type 1 (11b-HSD1) and Glucocorticoid Receptor (GR) Proteins on Fetal Sheep Liver During Late Gestation. J Endocrinol. 176(2):175-84 (2003)
- Gupta S, Gyomorey S, Lye SJ, Gibb W, Challis JRG. Effect of Labor on Glucocorticoid Receptor (GRTotal, GRa, and GRb) Proteins in Ovine Intrauterine Tissues. J Soc. Gynecol Investig. 10(3):136-44 (2003)
- Alfaidy N, Sun M, Challis JRG, Gibb W. Expression of Membrane Prostaglandin E Synthase (mPGES) in the Human Placenta and Fetal Membranes and the Effect of Labor. Endocrine. 20(3):219-26 (2003)
- Premyslova M, Li W, Alfaidy N, Bocking AD, Campbell K, Gibb W, Challis JR. Differential Expression and Regulation of Microsomal Prostaglandin E(2) Synthase in Human Fetal Membranes and Placenta with Infection and in Cultured Trophoblast Cells. J Clin Endocrinol Metab. 2003;88(12):6040-7
- M. Sun, J. Kingdom, D. Baczyk, S. J. Lye, S. G. Matthews, and W. Gibb1. Expression of the Multidrug Resistance P-Glycoprotein, (ABCB1 glycoprotein)) in the Human Placenta Decreases with Advancing Gestation Placenta (2005) in press.
- Kalabis, G. M. Kostaki, A., Andrews, M.H., Petropoulos, S., Gibb, W. and Matthews, S.G. . Multidrug Resistance Phosphoglycoprotein (ABCB1) in the Mouse Placenta: Fetal Protection Biology of Reproduction (2005) in press.
Papers In Refereed Conference Proceedings
- Challis JRG, Lye SJ, Gibb W, Whittle W, Patel F, Alfaidy N. Understanding Preterm labor. Human Fertility and Reproduction: The Oocyte, the Embryo and the Uterus. Ann NY Acad Sci. 943: 225-234 (2001)
- Gibb W, Challis J, Lye S, Whittle W, Patel F, Alfaidy N. Pathophysiology of Preterm Birth. Clinical Relevance. Proceedings World Congress of Perinatal Medicine. p.651-656 (2001).
- Challis JRG, Sloboda D, Alfaidy N, Lye SJ, Gibb W, Patel FA, WhittleWL and Newnham JP. Prostaglandins and mechanisms of preterm birth. Reproduction. 2002;124(1):1-17.
- Gibb W, Challis JRG. Endocrinology of Parturition. In Jameson and De Groot Endocrinology 5th Edition. Ed. D. de Kretser. (2005) in press.
- Gibb W, Lye S.J.,Challis JRG. Parturition. In 3rd edition: The Physiology of Reproduction. Ed. Knobil and Neill J.D. (2005) in press
- Gibb W, and Challis JRG. Human Parturition and Birth. In Nature Encyclopedia of Life Sciences (2005) in press.