The Role of Biglycan in Reproduction

描述(由申请人提供)：早产是美国新生儿发病率的主要原因。尽管多次尝试干预，但在过去20年中，早产儿的发生率并没有明显改善。早产胎膜早破(PPROM)是导致早产的重要原因。在小鼠模型中，Biglycan的表达缺陷与Ehler-Danlos综合征样表型有关。Biglycan是一种细胞外基质小的富含亮氨酸的蛋白多糖，在妊娠组织中高度表达。这种综合征与胎膜早破的发生率增加有关。此外，参与细胞外基质降解并参与PPROM发病机制的基质金属蛋白酶与包括二聚糖在内的蛋白多糖相互作用。因此，这项建议的长期目标是阐明Biglycan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开发PPROM治疗方法的垫脚石。这位首席研究员在德国法兰克福的约翰·沃尔夫冈·歌德大学获得了医学博士学位，在那里她的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。她的奖学金研究得到了NICHD儿科科学家发展计划的支持，重点是大聚糖在肌肉发育过程中的功能。这一赞助奖项的目标是支持候选人发展成为一名成熟的内科科学家，成功地弥合她作为新生儿专家的基础科学研究和临床兴趣之间的差距。她将能够利用布朗大学丰富的研究和培训环境，通过课程作业、研讨会和与成功和知名的基础科学家以及内科科学家一起直接指导研究计划来实现这一目标。

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.