Inflammatory Mechanisms of Puberty Dysregulation in Colitis

描述（由申请人提供）：该临床科学家职业奖将支持弗吉尼亚大学（UVa）儿科内分泌学家Mark D. DeBoer医学博士的发展，他将继续在临床导向的基础科学研究方面进行培训。DeBoer博士将由Steve Cohn博士指导，Steve Cohn博士是炎症性肠病和免疫学领域的知名研究人员。这项培训将使DeBoer博士获得独立研究人员所需的知识和技能。为此，该申请概述了一个职业发展计划，包括介绍消化健康评估、神经科学和基因表达分析方面的新实验室技术。DeBoer博士还将接受神经科学、遗传学、生物统计学和研究伦理方面的全面指导；这将部分通过弗吉尼亚大学研究生科学学院和健康评估科学系的课程来实现。DeBoer博士的研究计划旨在加强对炎症性肠病（IBD）中神经内分泌异常病因的理解，IBD是儿科中相对常见的慢性疾病。当IBD发生在青春期之前时，通常会导致青春期开始的延迟，导致骨密度下降，最终成人身高下降和自尊丧失。DeBoer博士的研究调查了系统性和中枢神经系统炎症对下丘脑-垂体-性腺轴的影响，这是导致青春期延迟的原因之一。他的建议进一步试图确定抗炎治疗是否会使结肠炎期间的青春期时间正常化。除了Cohn博士的指导外，DeBoer博士还有一个优秀的咨询委员会，他将接受Daniel Marks博士的神经科学指导，Daniel Marks博士是俄勒冈健康与科学大学（Oregon Health & Science University）的儿科内分泌学家和成功的基础科学导师。这项研究将在最先进的实验室进行，并与科学探究和数据分析方面的教学培训相结合，将使DeBoer博士成为肠道炎症和生殖内分泌学领域的独立临床研究员。

DESCRIPTION (provided by applicant): This Clinical Scientist Career Award will support the development of Mark D. DeBoer, MD, a pediatric endocrinologist at the University of Virginia (UVa) as he continues to train in clinically-oriented basic science research. Dr. DeBoer will be mentored by Dr. Steve Cohn, a well-known researcher in the fields of inflammatory bowel disease and immunology. This training will allow Dr. DeBoer to acquire the knowledge and skills needed by an independent researcher. To this end, the application outlines a career development plan that includes introduction to new laboratory techniques in both digestive health evaluation, neuroscience and gene expression analysis. Dr. DeBoer will also receive comprehensive instruction in neuroscience, genetics, biostatistics, and research ethics; this will occur in part through the courses in the UVa Graduate Sciences School and the Dept. of Health Evaluation Sciences. Dr. DeBoer's research proposal is designed to enhance understanding of the etiology of neuroendocrine abnormalities in inflammatory bowel disease (IBD), a relatively common chronic disease in pediatrics. When IBD occurs prior to puberty, it often results in a delay in the onset of puberty, leading to a decrease in bone mineral density, a decrease in final adult height and a loss of self-esteem. Dr. DeBoer's research investigates the effects of systemic and central nervous system inflammation on the hypothalamic-pituitary-gonadal axis as a cause of this delay in puberty. His proposal further attempts to identify whether anti-inflammatory treatment will normalize the timing of puberty during colitis. In addition to his mentorship by Dr. Cohn, Dr. DeBoer has an excellent Advisory Committee and he will receive mentorship in neuroscience from Dr. Daniel Marks, a pediatric endocrinologist and successful basic-science mentor at Oregon Health & Science University. The research will be performed in state-of-the-art laboratories and, in conjunction with didactic training in scientific inquiry and data analysis, will permit Dr. DeBoer's development into an independent clinician-investigator in the fields of intestinal inflammation and reproductive endocrinology. PUBLIC HEALTH RELEVANCE: Inflammatory bowel disease (IBD) is comprised of Crohn's disease and ulcerative colitis. In children and adolescents, IBD can cause a delay in puberty, leading to weak bones, shorter final height and decreased self esteem. This proposal seeks to discover whether delayed puberty in IBD is a result of inflammation and whether the timing of puberty in IBD can be improved by treating with medications that block inflammation.