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Medical Research Council Human Reproductive Sciences Unit |
'Leading Science for Better Health'
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| Dr Henry N. Jabbour Principal Investigator | Contact | |
 Research focus This programme of research aims: 1. To investigate the role of cyclooxygenase enzymes, prostaglandins and their receptors in regulation of endometrial function. This programme also aims to elucidate the signalling pathways and target genes that mediate the role of prostaglandins and their receptors in dysregulation of vascular function in pathologies of the female reproductive tract using both in vitro and in vivo model systems. 2. To elucidate the exact role and mode of action of a newly discovered family of angiogenic factors termed the prokineticins and their receptors. These factors are widely expressed in the non-pregnant female reproductive tract and during pregnancy. Background to the research The human endometrium undergoes cyclical changes in order to prepare for implantation. In the absence of conception, the endometrium is shed at menstruation and a new menstrual cycle begins. Central to proper endometrial function in preparation for implantation is the proper organisation of the vascular bed (a process referred to as angiogenesis). Angiogenesis rarely occurs in the healthy non-pregnant adult except in women of reproductive age where recurring cycles of blood vessel growth and differentiation occur in the ovary and endometrium every menstrual cycle. In the absence of pregnancy, the endometrium is shed at menstruation. After menstruation, the endometrium is replenished and repair of the vascular bed is reinitiated in preparation for a new menstrual cycle. This process involves focal extracellular matrix reorganisation, endothelial cell proliferation, migration and organisation into capillary networks. Many of the pathologies of the female reproductive tract (such as cancer, endometriosis, excessive menstrual blood loss) are associated with dysregulation of vascular function. Angiogenesis and vascular function/permeability in the human endometrium is controlled by a finely tuned pattern of expression of angiogenic and anti-angiogenic genes. For many years, prostaglandins have been recognised as key molecules in reproductive biology by regulating ovarian and endometrial physiology. Similarly, the newly discovered family of prokineticins (termed prokineticin 1 and prokineticin 2) and their two distinct GPCR receptors (termed prokineticin receptor 1 and prokineticin receptor 2) have been implicated in vascular function of the reproductive tract. More recently, we have ascertained a role for cyclooxygenase enzymes and prostaglandins in various pathologies of the reproductive tract. The potential roles of prokineticins and their receptors in vascular function of the female reproductive tract and its pathologies remain to be elucidated.Recent Progress
Figure 1. Autocrine/paracrine regulation of angiogenesis, cell adhesion and migration by prostanoid receptor signalling.  |
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h.jabbour@hrsu.mrc.ac.uk Tel: +44 (0)131 242 6220 Fax: +44 (0)131 242 6197 |
| Publications | ||
| Publications - full listing | ||
| Publications - Selected; recent | ||
| Gametogenesis | ||
| Research Programmes | ||
| Prostaglandin signalling and function in uterine physiology and pathology | ||
| Manipulation of angiogenesis and vascular permeability in the corpus luteum and uterus | ||
| Research Staff | ||
Dr Jabbour's research group currently comprises 1 Senior Investigator Scientist, 1 Career Development Fellow, 4 research support staff and 2 PhD students. |
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| Editorships/Affiliations/Collaborations | ||
| Member of the Editorial Board of "Reproduction" and "Journal of Endocrinology". |
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Member of the Council of Management of the Society for Reproduction and Fertility. |
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Programme Secretary for the Society for Reproduction and Fertility. |
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Long standing collaborations with numerous leading laboratories in the UK and overseas including South Africa , Europe and USA. |
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Member of numerous societies within the UK and USA. |
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Honorary fellow of The University of Edinburgh and The University of Cape Town. |
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| Selected recent publications | ||
Jabbour, H.N., Kelly , R.W., Fraser, H.M. and Critchley, H.O.D. (2006). Endocrine regulation of endometrial function. Endocrine Reviews 27: 17-46. Muller, M., Sales, K.J., Katz, A.A. and Jabbour, H.N. (2006). Seminal plasma promotes the expression of tumorigenic and angiogenic genes in cervical adenocarcinoma cells via the E-series prostanoid 4 receptor. Endocrinology 147: 3356-3365. Sales, K.J., List, T., Boddy, S.C., Williams, A.R.W., Anderson , R.A., Naor, Z. and Jabbour, H.N. (2005). A novel angiogenic role for prostaglandin F 2a -FP receptor interaction in human endometrial adenocarcinoma. Cancer Research 65: 7707-7716. Jabbour, H.N. and Sales, K.J. (2004). Prostaglandin receptor signalling and function in human endometrial pathology. Trends in Endocrinology and Metabolism 15: 398-404. Sales, K.J., Maudsley S. and Jabbour, H.N. (2004). Elevated prostaglandin EP2 receptor in endometrial adenocarcinoma cells promotes VEGF expression via cAMP-meidated transactivation of the EGF receptor and ERK1/2 pathways. Molecular Endocrinology 18: 1533-1545. Sales, K.J., Katz, A.A., Howard, B., Soeters, R.P, Millar, R.P. and Jabbour, H.N. (2002). Cyclooxygenase-1 is up-regulated in cervical carcinomas: Autocrine/paracrine regulation of cyclooxygenase-2, PGE receptors and angiogenic factors by cyclooxygenase-1. Cancer Research 62: 424-432. |
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Figure 1.
Autocrine/paracrine regulation of angiogenesis, cell adhesion and migration by prostanoid receptor signalling. |
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In this cartoon, prostaglandins (produced either intracellularly via the COX enzyme biosynthetic pathway or present in seminal plasma) activate specific prostanoid receptors, initiating second messenger production (inositol 1,4,5 trisphosphate, IP3). Activation of the second messenger systems can initiate signalling via the small G-protein Ras-extracellular signal-regulated kinase (ERK1/2) pathway to initiate target gene transcription via transactivation of the EGF receptor (EGFR). Small monomeric G proteins such as Rho, Rac and CDC42 can also be activated to alter cell adhesion via the activation of focal adhesion kinase (FAK) and integrin-extracellular matrix (ECM) interaction. |
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