The Role of Biglycan in Reproduction

双糖链蛋白聚糖在生殖中的作用

• 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
• 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' 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

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。尽管有许多干预的尝试，早产的发生率在过去的二十年里没有明显的改善。早产胎膜早破（PPROM）是早产的一个重要的潜在原因。在小鼠模型中，biglycan（一种在妊娠组织中高度表达的细胞外基质小的富含亮氨酸的蛋白多糖）的表达缺陷与ehers - danlos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，一种参与细胞外基质降解的酶，与PPROM的发病机制有关，可与包括biglycan在内的蛋白聚糖相互作用。因此，这一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。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医学博士学位，在那里她的博士论文包括前列腺生殖生物学研究，在西北医院完成了妇产科实习培训，在布朗大学妇女和婴儿医院完成了奖学金培训。她的研究得到了NICHD儿科科学家发展项目的支持，主要研究biglycan在肌肉发育过程中的功能。这个赞助奖项的目标是支持候选人发展成为一个成熟的内科科学家，成功地弥合了她的基础科学研究和她作为新生儿学家的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，通过课程学习，研讨会，以及与成功和成熟的基础科学家以及医师科学家的研究计划的直接指导来实现这一目标。