Duke Maternal-Fetal Medicine Specialist Chad Grotegut, MD, MHSc, MBA, and cardiologist Paul Rosenberg, MD, have been awarded a multiple principal investigator R01 grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The grant, which is titled The role of calcium homeostasis in regulating uterine contractility and tone, is valued at over $3.2 million and seeks to identify the molecular mechanisms associated with abnormal term labor.
Prevention of the primary cesarean delivery is a central goal in modern obstetric care as the cesarean delivery rate in the United States has steadily risen over the last 20 years. The current cesarean delivery rate is thought to be higher than the optimal rate that balances maternal and neonatal outcomes, Dr. Grotegut notes.
"National initiatives to prevent the primary cesarean delivery have yet to make substantial impact, but preventing the primary cesarean delivery is an important goal as once women have a cesarean delivery, they are likely to have repeat cesarean deliveries in subsequent pregnancies," said Dr. Grotegut.
The most common indication for cesarean delivery is dysfunctional uterine contractions, which is also referred to as labor dystocia, or abnormal labor, and the etiology of abnormal labor remains largely unknown. Drs. Grotegut and Rosenberg’s proposal seeks to better understand normal and abnormal uterine contraction in term labor by studying the role of an intracellular calcium sensor – stromal interaction molecule 1 (STIM1). STIM1 is important for regulating intracellular calcium levels during periods of repeated muscle contraction. In addition, STIM1 is also an important regulator of metabolic flexibility and prevention of muscle fatigue. Abnormal expression or inappropriate function of STIM1 may result in a uterine smooth muscle phenotype that is not able to appropriately circulate needed calcium within the cell, or may cause the muscle cells to not be able to meet the metabolic demands of an exercising organ. Both of these findings could result in uterine muscle and uterine tissue that does not adequately contract during labor.
Much of the preliminary data included in the proposal was generated by Duke Ob/Gyn resident Chelsea Feldman, MD, while she was a Duke Medical student. Her work was funded through the Howard Hughes Medical Research Fellows program and was mentored by Drs. Grotegut and Rosenberg. Dr. Feldman plans to continue her work in the laboratory as part of her resident research project.
With the support of this R01 grant by the NIH, the Grotegut and Rosenberg laboratories will hopefully establish a novel paradigm for uterine contractility in term labor and aid in the development of novel therapies for labor dystocia.