The Role of the Enteric Nervous System in Necrotizing Enterocolitis

肠神经系统在坏死性小肠结肠炎中的作用

• 批准号: 9543488
• 负责人: Bradley J Segura
• 金额: $ 19.85万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9543488
• 关键词: Ablation; Adult; Advisory Committees; Affect; Categories; Cells; Child; Childhood; Clinical; Committee Members; Data; Development; Disease; Elements; Enteral; Enteric Nervous System; Environment; Epithelial; Equilibrium; Etiology; Event; Gatekeeping; Goals; Growth Factor; Human; In Vitro; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Intestinal Diseases; Intestines; Laboratories; Life; Lipids; Maintenance; Mediating; Medical; Mentors; Minnesota; Modeling; Mus; Necrotizing Enterocolitis; Neuroglia; Neurons; Newborn Infant; Operative Surgical Procedures; Pathway interactions; Patients; Pediatric Surgical Procedures; Population; Premature Infant; Prevention; Preventive; Research; Research Personnel; Resources; Risk; Role; Scientist; Signal Pathway; Signal Transduction; Signaling Molecule; Sphingolipids; Sphingosine-1-Phosphate Receptor; Surgeon; Survivors; Testing; Therapeutic; Training; United States; Universities; Ursidae Family; Very Low Birth Weight Infant; Veterinary Schools; Work; base; career; design; experience; improved; in vivo; insight; interdisciplinary approach; interest; medical schools; mortality; neurotransmission; novel therapeutics; premature; professor; public health relevance; skills; sphingosine 1-phosphate; targeted treatment

 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.

 个人描述(申请人提供)：我是明尼苏达大学儿科外科外科助理教授。虽然作为一名儿科外科医生，我管理的儿科疾病范围很广，但我对肠道神经系统(ENS)在肠道炎症和疾病中的作用产生了主要的兴趣。在我的综合医学培训期间，我的博士论文描述了鞘磷脂信号在肠神经胶质细胞中的作用，特别强调鞘氨醇-1-磷酸(S1P)。我的长期职业目标是成为一名成熟的独立研究员，并为患有坏死性小肠结肠炎(NEC)等衰弱肠道疾病的儿童开发更好的治疗方案。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高效的学术环境中与我在大学里的其他顾问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校内外的最先进资源，使我们能够揭开一些EN在肠道炎症和疾病中所起作用的奥秘。研究：坏死性小肠结肠炎对早产儿来说是一个毁灭性的且日益严重的困境。最近的证据表明，肠神经胶质细胞可能在肠道中充当守门人，在那里它们可能有助于调节成人和儿童的炎症性疾病。这项建议试图在NEC的背景下进一步深入了解鞘磷脂信号转导肠道神经胶质细胞的情况。我们的研究表明，S1P的肠道神经胶质细胞受体和这些受体耦合到下游细胞事件，这可能被证明是发育成熟的肠道神经系统儿童维持肠道屏障完整性所不可或缺的。目的1：证实肠神经胶质细胞信号转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细胞信号不发达，导致肠屏障功能障碍。摘要：这份K08提案在我之前的研究经验的基础上进行了合乎逻辑的进步，通过我的顾问的指导，整合了其他基本技能的发展。此应用程序旨在促进作为指导科学家的晋升为 一位独立的外科科学家，主要目的是进一步确定生物活性的作用 小儿炎症性肠病，如坏死性小肠结肠炎，肠神经系统神经胶质细胞中的脂质信号。