The Role of Biglycan in Reproduction

描述（由申请人提供）：早产是美国新生儿发病的主要原因。 尽管进行了多次干预尝试，但早产发生率在过去二十年中没有显着改善。 早产胎膜早破（PPROM）是早产的重要原因。 在小鼠模型中，双糖链蛋白聚糖（一种在妊娠组织中高度表达的细胞外基质富含亮氨酸的小蛋白聚糖）表达缺陷与Ehlers-Danlos综合征样表型相关。 这种综合征与PPROM的发病率增加有关。 此外，基质金属蛋白酶，即参与细胞外基质降解并与PPROM的发病机制有关的酶，与包括双糖链蛋白聚糖在内的蛋白聚糖相互作用。 因此，本提案的长期目标是阐明双糖链蛋白聚糖在成功妊娠中发挥作用的具体机制，希望我们的见解可以作为PPROM治疗方法开发的垫脚石。 首席研究员获得了医学博士学位。在德国法兰克福的约翰·沃尔夫冈·歌德大学，她的博士论文包括前列腺素生殖生物学研究，在西北医院完成了产科/妇科实习培训，在布朗大学妇女和婴儿医院完成了奖学金培训。 她的奖学金研究，这是由NICHD儿科科学家发展计划的支持，重点是在肌肉发育过程中的biglycan的功能。 这个赞助奖项的目标是支持候选人发展成为一个既定的医生，科学家谁成功的桥梁之间的差距差距，她的基础科学研究和她的临床利益作为一个兽医。 她将能够通过利用布朗大学丰富的研究和培训环境，通过课程，研讨会和直接指导研究计划与成功和建立基础科学家以及医生科学家来实现这一目标。

DESCRIPTION (provided by applicant): 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.