The overall objective of the Mitchell laboratory is to develop pharmacological agents that might be clinically useful in the prevention or treatment of preterm labor.
Over the past three decades, the Mitchell laboratory has explored the paracrine network within the late pregnant uterus to better understand its role in the regulation of the timing of parturition. Our early work documented steroid hormone production and metabolism in chorion and decidua. We pioneered the concept and were first to demonstrate synthesis of uterine agonist peptide hormones (oxytocin, endothelin) in human decidua. We then studied mechanisms regulating gene expression for several genes associated with the process of uterine activation, which occurs just prior to parturition.
Our more recent studies have focused on the molecular events that regulate contractility of uterine myocytes. Our primary focus is on the human uterine myocyte but we also have made extensive use of the rat model for term and anti-progestin-induced preterm labor. Most recently, we have developed and characterized the guinea pig as a potentially better model for human parturition.
We currently are investigating the role of RhoA-associated kinase and its associated pathways on the regulation of uterine contractility. These studies include determining the potential role of a variety of small molecule kinase inhibitor to prevent or arrest preterm labor in rat and guinea pig models. Lab technologist Barbara Zielnik and post-doctoral Fellow Mei Chi are leading these studies.
Chibbar, R., Miller, F.D., Mitchell, B.F. Synthesis of oxytocin in amnion, chorion, and decidua may influence the timing of human parturition. Journal of Clinical Investigation 91:185-92, 1993.
Mitchell, B.F., Taggart, M.J. Are animal models relevant to key aspects of human parturition? American Journal of Physiology Regulatory Integrative and Comparative Physiology 297:R525-R545,2009.
Taggart, M. J., Arthur, P., Zielnik, B., Mitchell, B. F. Molecular pathways regulating contractility in the rat uterus through late gestation. American Journal of Obstetrics and Gynecology 207(1):76.e15-24;2012
Aguilar, H. N., Tracey, C. N., Zielnik, B., Mitchell, B. F. Rho kinase mediates diphosphorylation of myosin regulatory light chain in uterine but not vascular smooth muscle. Journal of Cellular and Molecular Medicine 16(12):2978-89,2012. doi: 10.1111/j.1582-4934.2012.01625