Preterm delivery is the leading cause of newborn morbidity in the United States. Despite numerous attempts at intervention, the incidence of prematurity has shown no significant improvement over the last two decades. Preterm premature rupture of membranes (PPROM) is a significant underlying cause of premature delivery. In the mouse model, defects in the expression of biglycan, an extracellular matrix small leucine-rich proteoglycan that is highly expressed in gestational tissues, are associated with an Ehlers-Danlos syndrome-like phenotype. This syndrome is associated with an increased incidence of PPROM. Furthermore, matrix metalloproteinases, enzymes which are involved in degradation of the extracellular matrix and which have been implicated in the pathogenesis of PPROM, interact with proteoglycans including biglycan. Thus, the long range goal of this proposal is to elucidate the specific mechanisms by which biglycan plays a role in successful gestation in the hope that our insights may serve as a stepping stone towards the development of therapies for PPROM. The principal investigator earned her M.D. at Johann Wolfgang Goethe University, Frankfurt, Germany, where her dissertation thesis consisted of prostaglandin reproductive biology research, completed internship training in obstetrics/gynecology at Nordwest Hospital, fellowship training at Brown University Women and Infants'Hospital. Her fellowship research, which was supported by the NICHD Pediatric Scientist Development Program, was focused on the function of biglycan in muscle during development. The goal of this sponsored award is to support the candidate in developing into an established physician-scientist who successfully bridges the gap between her basic science research and her clinical interests as a neonatologist. She will be able to accomplish this by taking advantage of the rich research and training environment at Brown University through coursework, seminars, and direct mentoring of the research plan with successful and established basic scientists as well as physician-scientists.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Clinical Investigator Award (CIA) (K08)
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Pediatrics Subcommittee (CHHD)
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Ilekis, John V
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Women and Infants Hospital-Rhode Island
United States
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Wu, Zhiping; Horgan, Casie E; Carr, Olivia et al. (2014) Biglycan and decorin differentially regulate signaling in the fetal membranes. Matrix Biol 35:266-75
Horgan, Casie E; Roumimper, Hailey; Tucker, Richard et al. (2014) Altered decorin and Smad expression in human fetal membranes in PPROM. Biol Reprod 91:105
Wu, Zhiping; Aron, Abraham W; Macksoud, Elyse E et al. (2012) Uterine dysfunction in biglycan and decorin deficient mice leads to dystocia during parturition. PLoS One 7:e29627
Calmus, Megan L; Macksoud, Elyse E; Tucker, Richard et al. (2011) A mouse model of spontaneous preterm birth based on the genetic ablation of biglycan and decorin. Reproduction 142:183-94