The Role of Biglycan in Reproduction

双糖链蛋白聚糖在生殖中的作用

基本信息

批准号：
8410119
负责人：
Beatrice Elizabeth Lechner
金额：
$ 10.8万
依托单位：
WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-08 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8410119
关键词：
Address Animals Award Basic Science Binding Biological Biomechanics Breeding Calculi Childhood Clinical Collagen Fibril Collagen Type VI Connective Tissue Core Protein Data Defect Development Discipline of obstetrics Doctor of Medicine Ehlers-Danlos Syndrome Environment Enzymes Extracellular Matrix Extracellular Matrix Degradation Failure Fellowship Fetal Membranes Fetal Resorption Germany Glycosaminoglycans Goals Gynecology Hospitals Human Incidence Infant Internships Interstitial Collagenase Intervention Knock-out Knockout Mice Lead Leucine Leucine-Rich Repeat Link Maintenance Matrix Metalloproteinases Mentors Modeling Morbidity - disease rate Mus Muscle Mutation National Institute of Child Health and Human Development Newborn Infant Outcome Pathogenesis Peptide Hydrolases Phenotype Physicians Placenta Play Pre-Eclampsia Pregnancy Pregnant Uterus Premature Birth Principal Investigator Production Program Development Prostaglandins Proteins Proteoglycan Reproduction Reproductive Biology Research Research Training Role Scientist Secondary to Side Syndrome Tendon structure Testing Thick Tissues Training Umbilical vein United States Universities Variant Wharton&apos s jelly Woman Xylosylprotein 4-beta-galactosyltransferase biglycan collagenase collagenase 3 decorin insight interest mortality mouse model premature preterm premature rupture of membranes reproductive reproductive function therapy development tissue processing

项目摘要

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.

描述（由申请人提供）：早产是美国新生儿发病率的主要原因。尽管进行了许多干预尝试，但在过去的二十年中，早产的发生率没有显着改善。早产膜（PPROM）是过早递送的重要原因。在小鼠模型中，Biglycan表达的缺陷是一种在妊娠组织中高度表达的细胞外基质小蛋白聚糖，与Ehlers-Danlos综合征样表型有关。该综合征与PPROM的发生率增加有关。此外，基质金属蛋白酶，参与细胞外基质降解的酶，与PPROM的发病机理有关，与包括大型群体在内的蛋白聚糖相互作用。因此，该提案的远距离目标是阐明大型群岛在成功妊娠中发挥作用的特定机制，希望我们的见解可以作为开发PPROM治疗的垫脚石。这位首席研究员在德国法兰克福约翰·沃尔夫冈·戈德大学（Johann Wolfgang Goethe University）赢得了医学博士学位，她的论文论文由前列腺素生殖生物学研究组成，完成了Nordwest医院的妇产科/妇科学的实习培训，在棕色大学妇女和婴儿医院进行培训。她的奖学金研究得到了NICHD儿科科学家发展计划的支持，该研究的重点是发展过程中Biglycan的功能。这项赞助奖的目标是支持候选人发展成一个知名的医师科学家，她成功地弥合了她的基础科学研究与新生儿学家临床利益之间的差距。她将能够通过课程，研讨会，直接指导成功的基础科学家以及医师科学家，通过课程工作，直接指导研究计划来实现这一目标。