Terrence K. Allen, MBBS – 2015

2015 DIG Research Projects | “The Role of Progestins and PGRMC1 in Inflammation-Induced Fetal Membrane Weakening”

Background

I grew up in Montego Bay and earned my medical degree from the University of the West Indies medical school in Jamaica. My interest in both anesthesia and obstetrics began during my internship at the Cornwall Regional Hospital in Montego Bay. As a new intern, providing health care to high-risk pregnant women on a busy delivery unit with limited resources was extremely challenging. However, this first-hand experience with adverse maternal and neonatal outcomes associated with preterm delivery, preeclampsia, major obstetric hemorrhage, and obstetric anesthesia complications drives my research interests today.

I completed my anesthesiology residency in West Yorkshire and Manchester, England, where I worked in a multidisciplinary environment with obstetricians and neonatologists during my obstetric anesthesiology rotations. These experiences solidified my decision to pursue an obstetric anesthesiology fellowship.

Fellowship training in obstetric anesthesia at Duke University Medical Center enhanced my clinical skills and expertise in managing high-risk obstetric patients, and importantly, introduced me to research. During this one-year fellowship, my research focused on methods to reduce or eliminate hypotension, nausea, and vomiting, common complications associated with spinal anesthesia for cesarean delivery. This experience laid the groundwork for my research career.

Research

My interest in preterm delivery, delivery before 37 weeks of pregnancy, began as a faculty member at Duke University Medical Center where I worked side by side with Duke obstetricians and neonatologists. It was there that I became increasingly aware of the scope of the clinical problem of preterm premature rupture of membranes (PPROM), rupture of fetal membranes before 37 weeks and a leading cause of preterm delivery. Additionally, it highlighted the need to clarify underlying mechanisms involved in PPROM in order to develop effective therapeutic strategies.

Working with my mentor, Dr. Amy Murtha, and using a cell line, which has similar characteristics to the cells of fetal membranes, we identified that progestin therapy inhibits inflammatory pathways that lead to PPROM through a novel progesterone receptor PGRMC1. PGRMC1 is also found in human fetal membranes instead of the nuclear progesterone receptor, which was previously thought to be responsible for the effects of progestins in the reproductive tract. These exciting findings highlight a new role for PGRMC1 in human fetal membranes as a possible therapeutic target for preventing PPROM.

The funding received from the DREAM Campaign will help to accelerate the work in this new area of research in preterm delivery, which will be performed in collaboration with Dr. Irina Buhimschi, a reproductive biologist from the Ohio State University. It will allow us to determine the role of progestin therapy and PGRMC1 on the inflammatory pathways that lead to weakening of fetal membranes prematurely. These results will generate preliminary data, which will form the basis for further NIH and foundation grant funding. Most importantly, our work has the potential to change the paradigm of thinking in this area of research. I am extremely appreciative of the support that the DREAM Campaign has provided for my research as I work tirelessly to translate my laboratory findings into meaningful clinical outcomes.