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：
7587557
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/7587557
关键词：
Address Animals Award Basic Science Binding Biological Biomechanics Breeding Calculi Childhood Clinical Collagen Collagen Fibril 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 Premature Rupture Fetal Membranes 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的主要原因。尽管进行了多次干预尝试，但在过去二十年中，早产的发生率并没有显着改善。胎膜早破（PPROM）是早产的一个重要根本原因。在小鼠模型中，双聚糖（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）表达缺陷与埃勒斯-当洛斯综合征样表型相关。该综合征与 PPROM 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并与PPROM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，该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成为开发 PPROM 疗法的垫脚石。主要研究者在德国法兰克福约翰沃尔夫冈歌德大学获得医学博士学位，她的论文包括前列腺素生殖生物学研究，在西北医院完成了妇产科实习培训，在布朗大学妇婴医院完成了进修培训。她的奖学金研究得到了 NICHD 儿科科学家发展计划的支持，重点研究双糖链蛋白聚糖在肌肉发育过程中的功能。该奖项的目的是支持候选人发展成为一名成熟的医师科学家，成功弥合基础科学研究与新生儿科医生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、研讨会以及与成功且成熟的基础科学家以及医师科学家对研究计划的直接指导来实现这一目标。