The Role of the Enteric Nervous System in Necrotizing Enterocolitis

 描述（由申请人提供）：我是明尼苏达大学儿科外科系的助理教授。虽然我作为一名儿科外科医生管理广泛的儿科疾病，但我对肠神经系统（ENS）在肠道炎症和疾病中的作用感兴趣。我的博士论文在我的综合医学培训的特点鞘脂信号在肠神经胶质细胞的作用，特别强调鞘氨醇-1-磷酸（S1 P）。我的长期职业目标是成为一名成熟的独立研究者，并为患有坏死性小肠结肠炎（NEC）等衰弱性肠道疾病的儿童开发改进的治疗方案。工作环境：我的主要导师萨比塔·罗伊博士和我在一个充满热情和富有成效的学术环境中与我在整个大学的其他咨询委员会成员一起工作。我们的跨学科方法涉及医学院和兽医学院内外的最先进的资源，使我们能够解开ENS在肠道炎症和疾病中的作用的一些奥秘。研究：坏死性小肠结肠炎对早产儿来说是一个毁灭性的和不断上升的困境。最近的证据表明，肠神经胶质细胞可以作为肠道中的看门人，在那里它们可以帮助调节成人和儿童的炎症性疾病。该提案旨在进一步深入了解神经鞘脂信号肠神经胶质细胞的背景下，NEC。我们的研究表明，肠神经胶质细胞承担S1 P受体，这些受体与下游细胞事件偶联，这可能是维持肠神经系统发育成熟的儿童肠道屏障完整性不可或缺的。目的1：证明肠神经胶质细胞信号传导有助于儿童正常的肠道屏障功能。目的2：证实坏死性小肠结肠炎患儿肠神经胶质信号不发达，导致肠屏障功能紊乱。总结：这个K 08提案是我以前在肠神经系统神经胶质细胞信号事件方面的研究经验的逻辑进展，通过我的顾问的指导整合了其他基本技能的发展。此应用程序的目的是促进作为一个指导科学家的进展， 一位独立的外科医生科学家，其主要目的是进一步表征生物活性物质的作用， 在儿童肠道炎症性疾病如坏死性小肠结肠炎中肠神经系统的胶质细胞中的脂质信号传导。

 DESCRIPTION (provided by applicant): I am an Assistant Professor in the Department of Surgery, Division of Pediatric Surgery, at the University of Minnesota. Although I manage a broad spectrum of pediatric disorders as a pediatric surgeon, I have developed a primary focus of interest in the role of the enteric nervous system (ENS) in intestinal inflammation and disease. My doctoral thesis during my combined medical training characterized the role of sphingolipid signaling in enteric glia, with particular emphasis on sphingosine-1-phosphate (S1P). My long- term career goal is to become an established independent investigator and to develop improved treatment options for children with debilitating intestinal diseases such as necrotizing enterocolitis (NEC). Environment: My primary mentor, Dr. Sabita Roy, and I work together in an enthusiastic and highly productive academic environment in conjunction with my other advisory committee members across the university. Our interdisciplinary approach involves state-of-the-art resources within the medical school and veterinary schools and beyond to allow us to unravel some the mysteries of the role of the ENS in intestinal inflammation and disease. Research: Necrotizing enterocolitis is a devastating and rising dilemma for premature infants. Recent evidence suggests that enteric glia may serve as gatekeepers in the intestine where they may help modulate inflammatory disorders in adults and children alike. This proposal seeks to gain further insight into sphingolipid signaling enteric glia in the context of NEC. Our studies demonstrate that enteric glia bear receptors for S1P and these receptors couple to downstream cellular events which may prove integral to the maintenance of gut barrier integrity in children with a developmentally mature enteric nervous system. Aim 1: Demonstrate enteric glial cell signaling contributes to normal gut barrier function in children. Aim 2: Establih that enteric glial signaling is undeveloped in children with necrotizing enterocolitis, contributin to disrupted gut barrier function. Summary: This K08 proposal serves as logical progression from my previous research experience in signaling events of glial cells the enteric nervous system, integrating the development of other essential skills though the guidance of my advisors. This application is designed to facilitate progression as a mentored scientist to that of an independent surgeon scientist with the chief aim of further characterizing the role of bioactive lipid signaling in glial cells of the enteric nervous system in childhood intestinal disorders of inflammation such as necrotizing enterocolitis.