Donna M Slater, PhD
(Imperial College, London, UK)
Scholar, Alberta Heritage Foundation for Medical Research
Assistant Professor, Physiology & Pharmacology
Phone: (403) 210 7660
Lab: (403) 210 3938
E-mail: dmslater@ucalgary.ca
Current Research Interests:
In obstetrics, abnormal or inappropriate myometrial contractions can cause major clinical problems such as pre-term labour or post-partum hemorrhage. Prostaglandins and their receptors have been widely implicated in the process of parturition, but underlying signaling pathways involved remain poorly understood. Our research focuses on the role and regulation of prostaglandin synthesis and prostaglandin receptor signaling within the uterus (and specifically the myometrial smooth muscle) during pregnancy and parturition.
Specific projects include:
- Functional characterization of the responses to prostaglandin E2 (PGE2) and the roles of the individual PGE2 (EP) receptors in different regions of the uterus.
- Defining the signaling pathway(s) by which PGE2 inhibits both contraction and inflammatory cytokine output in myometrial smooth muscle (MSM): The role of cAMP-dependent kinase protein kinase A (PKA). I am using an adenoviral mediated gene transfer of the highly selective inhibitor of PKA, protein kinase inhibitor a (PKIa) to investigate the role of PKA in MSM cells.
- Determining the role of the transcription factor NF-kB in the production of, and response to, PGE2 in myometrial smooth muscle.
Several techniques are employed for our studies and include:
- Molecular biological and biochemical studies using MSM cells as a model to identify the molecular signaling pathways of the prostaglandins.
- Simultaneous Ca2+ fluorescence technique and organ bath studies to relate changes in intracellular Ca2+ levels and contractility of myometrial tissue.
- In situ hybridization and Immuno-histology to identify and localize mRNA and protein expression of specific genes in the prostaglandin pathway.
Recent Publications
Hay, A., Wood, S., Olson, D.M., Slater, D.M. (2010). Labour is associated with decreased expression of the PGF2 receptor (PTGFR) and a novel PTGFR splice variant in human myometrium but not decidua. Mol Hum Reprod [Epub ahead of print] PubMed Link
Astle, S., Newton, R., Thornton, S., Vatish, M., Slater, D.M. (2007). Expression and regulation of prostaglandin E synthase isoforms in human myometrium with labour. Mol Hum Reprod 13: 69-75. PubMed Link
Markovic, D., Vatish, M., Gu, M., Slater, D.M., Newton, R., Lehnert, H., Grammatopoulos, D.K. (2007). The onset of labour alters corticotropin-releasing hormone type 1 receptor (CRH-R1) variant expression in human myometrium: Putative role of IL-1b. Endocrinology 148: 3205-3213. PubMed Link
Slater, D.M., Astle, S., Woodcock, N., Chivers, J., de Wit, N.C.J., Thornton, S., Vatish, M. and Newton, R. (2006). Anti-inflammatory effects of PGE2 in myometrial smooth muscle. Mol Hum Reprod 12: 89-97.
PubMed Link
Astle, S., Thornton, S., Slater, D.M. (2005). Expression and localisation of prostaglandin E2 receptors (EP) in human myometrium during pregnancy. Mol Hum Repro 11: 279-287. PubMed Link
Clarke, D.L., Belvisi, M.G., Smith, S.J., Yacoub, M.H., Meja, K.K., Newton, R., Slater, D.M., Giembycz, M.A. (2005). Prostanoid receptor expression by human airways smooth muscle cells and regulation of the secretion of granulocyte colony-stimulating factor. Am J Physiol Lung Cell Mol Physiol 288: L238-50. PubMed Link
Slater, D.M., Astle, S., Bennett, P.R., Thornton, S. (2004). Labour is associated with up regulation of secretory PLA2 type-IIA, but not cytosolic PLA2 type-IV, in human myometrium. Mol Hum Reprod 10: 799-804.
PubMed Link
Dalrymple, A., Slater, D.M., Poston, L., Tribe, R.M. (2004). Gestation and IL-1b up-regulate TrpC proteins, putative calcium channels, in pregnant human myometrium. J Clin Endo Metab 89:1291-1300. PubMed Link
Operating Funds
Canadian Institutes Health Research, Operating Grant: "PGE2 and the EP receptors in the human uterus during pregnancy and parturition" (2007-2011).
Alberta Heritage Foundation for Medical Research, Scholar (2007-2014).
AHFMR, Interdisciplinary Team Grant (Co-Investigator) Preterm births & Healthy Outcomes (PreHOT), (2008 - 2013).
Personnel
Andrea Hay MD/PhD (Leaders in Medicine Program)
Kelly Rainey (PhD Student)
Administrative Assistant: Marnie Cudmore, cudmore@ucalgary.ca, (403) 220-6765
Collaborators
Dr Robert Newton, Dept Cell Biology & Anatomy, University of Calgary.
Dr Stephen Wood, Dept Obstetrics & Gynaecology, University of Calgary,
Foothills Medical Centre.
Dr Rachel Tribe, King's College, St Thomas' Hospital, London, UK
Dr Manu Vatish, Warwick Medical School, UK.