BLR&D Research Career Scientist Award Application

BLR

• 批准号: 10451504
• 负责人: Pradeep K Dudeja
• 金额: --
• 依托单位: JESSE BROWN VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10451504
• 关键词: Acetates; Acute Diarrhea; Antibiotics; Antidiarrheals; Area; Attention; Award; Butyrates; Calcium Oxalate; Cell membrane; Chemicals; Chlorides; Chronic; Chronic Disease; Chronic diarrhea; Chronic stress; Colon; Dehydration; Diarrhea; Disease; Disease remission; Doctor of Philosophy; Down-Regulation; Electrolytes; Environment; Epithelial; Etiology; Functional disorder; Funding; Gastroenterology; Generations; Genetic Transcription; Goals; Health; Healthcare; Homeostasis; Hormones; Human; Impairment; In Vitro; Incidence; Infection; Inflammation; Inflammatory Bowel Diseases; Intervention; Intestines; Irritable Bowel Syndrome; Journals; Knock-out; Knowledge; Large Intestine; Lead; Liquid substance; Liver diseases; Maintenance; Mentors; MicroRNAs; Mission; Molecular; Morbidity - disease rate; Nature; Neurotransmitters; Nosocomial Infections; Organ Donor; Pathogenesis; Performance at work; Persian Gulf Syndrome; Post-Traumatic Stress Disorders; Probiotics; Propionates; Protein Kinase; Publishing; Rattus; Regulation; Reporting; Research; Research Peer Review; Research Personnel; Role; SLC26A3 gene; Scientist; Signal Pathway; Sodium Chloride; Solid; Stress; Structure; TNF gene; Techniques; Therapeutic; Therapeutic Intervention; Time; Tissues; Training; Transcriptional Regulation; Transgenic Mice; Traumatic Brain Injury; Tretinoin; United States National Institutes of Health; Universities; Veterans; Volatile Fatty Acids; War; Work; absorption; age related; apical membrane; basolateral membrane; career; clinically relevant; comorbidity; diarrheal disease; dysbiosis; enteric pathogen; foodborne infection; foodborne pathogen; gut microbes; gut microbiome; hepatocyte nuclear factor; improved; in vivo; intestinal epithelium; meetings; monolayer; mortality; mouse model; multidisciplinary; new therapeutic target; novel; patient population; programs; promoter; response; success; therapeutic target; tool; uptake; waterborne pathogen

This application is for a competitive renewal of the SRCS program of Dr. Pradeep K Dudeja. His program is focused on elucidating the mechanisms of regulation of electrolyte and fluid absorption in the human intestine in health and disease. His studies are aimed at understanding the pathophysiology of diarrheal diseases as it pertains to infectious diarrhea and inflammatory bowel diseases (IBD) associated diarrhea and to develop better therapeutic interventions. Diarrheal diseases are very common in our Veterans due to high incidence of IBD, infections and deployment related chronic illnesses and stress. Our program utilizes state-of-the-art approaches including human intestinal enteroids or mini guts and enteroid derived monolayers, organ-donor human intestine derived purified antipodal plasma membranes from various regions of the gut, in vitro molecular approaches and in vivo approaches utilizing knock out and transgenic mouse models to better understand the pathophysiology of diarrhea and to identify novel therapeutic targets. Our group has had a unique advantage of leading this field globally due to some of the pioneering techniques established by us using the organ donor human intestines. We have extensively published our work in over 220 original peer reviewed research articles in many prestigious journals in the field including Gastroenterology (impact factor 21) and J Clin Invest (12.3). We have also extensively defined the role of gut-microbe interactions in diarrheal diseases with respect to infectious diarrhea and the beneficial role of probiotics in these diseases. In addition, one of the key hallmarks of our program has been a multidisciplinary and collaborative nature of the research enterprise with a deep focus on mentoring new generation of VA and affiliated university investigators to enable them to establish their own independent research programs. We have been successful at both the fronts of making new discoveries in the field and mentoring new generation of young scientists and establishing a solid research environment at our local VA as well as at affiliated university. Our program has been continuously funded by multiple VA and NIH awards. This current application is intended to highlight the success of our program and requesting renewal of this SRCS program to continue the progress towards the new heights of success by nurturing and mentoring a new generation of investigators.

本申请是Pradeep K Dudeja博士的SRCS计划的竞争性更新。他的计划是 着重阐明人体肠道内电解质和液体吸收的调节机制 健康和疾病。他的研究旨在了解牙周病的病理生理学， 与感染性腹泻和炎症性肠病（IBD）相关的腹泻， 更好的治疗措施。腹泻病在我们的退伍军人中非常常见， IBD，感染和部署相关的慢性疾病和压力。我们的项目利用了最先进的 方法包括人肠类肠或微肠和类肠衍生的单层，器官供体 人肠源性纯化对足质膜，来自肠的不同区域，在体外 利用敲除和转基因小鼠模型的分子方法和体内方法， 了解腹泻的病理生理学，并确定新的治疗靶点。我们组有一个 由于我们建立的一些开创性技术，我们在全球领先该领域的独特优势 使用器官捐赠者的肠子。我们已经在220多个原始同行中广泛发表了我们的工作 回顾了该领域许多著名期刊上的研究文章，包括胃肠病学（影响因子 21)和J Clin Invest（12.3）。我们还广泛地定义了肠道微生物相互作用的作用， 关于感染性腹泻的疾病和益生菌在这些疾病中的有益作用。此外，本发明还提供了一种方法， 我们项目的主要特点之一是研究的多学科性和协作性 一家专注于指导新一代VA和附属大学调查人员的企业， 使他们能够建立自己的独立研究计划。我们在两个方面都取得了成功。 在该领域取得新发现和指导新一代年轻科学家的前沿， 在我们当地的退伍军人事务部以及附属大学建立一个坚实的研究环境。我们的计划 一直由多个VA和NIH奖项资助。本申请旨在强调 我们的计划取得成功，并要求更新本SRCS计划，以继续朝着 通过培养和指导新一代的调查人员，实现新的成功高度。