BLR&D Research Career Scientist Award Application

BLR

• 批准号: 10618281
• 负责人: Jian-Ying Wang
• 金额: --
• 依托单位: BALTIMORE VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618281
• 关键词: Acute; Address; Affect; Animal Model; Apoptosis; Area; Award; Bacteria; Baltimore; Binding Proteins; Blood; Cell Survival; Cell membrane; Cells; Clinic; Clinical; Collaborations; Critical Illness; Crohn' s disease; Development; Disease; Elements; Environment; Epithelial Cells; Epithelium; Event; Exhibits; Faculty; Functional disorder; Funding; Gene Expression; Gene Expression Profile; Genes; Genetically Modified Animals; Goals; Grant; Gut Mucosa; Health; Healthcare; Healthcare Systems; Hemorrhage; Homeostasis; HuR protein; Impaired healing; Inflammation; Injury; Intestinal Mucosa; K-Series Research Career Programs; Knock-out; Laboratories; Laboratory Research; Link; Maintenance; Mammalian Cell; Maryland; Mediating; Medical center; Mentors; MicroRNAs; Mission; Molecular; Mucous Membrane; Natural regeneration; Nucleic Acids; Operative Surgical Procedures; Pathologic; Pathology; Patients; Peer Review; Peptic Ulcer; Permeability; Physiological; Poison; Polyamines; Positioning Attribute; Process; Proliferating; Publishing; RNA; Regulation; Repression; Research; Research Personnel; Research Project Grants; STIM1 gene; Scientist; Seminal; Sepsis; Services; Shock; Signal Transduction; Stream; Stress; Techniques; Testing; Therapeutic; Tissues; Trans-Activators; Transcription Process; Transgenic Organisms; Translations; Trauma; Ulcer; Ulcerative Colitis; United States National Institutes of Health; Universities; Untranslated RNA; Veterans; WNT Signaling Pathway; base; career; cell motility; effective therapy; epithelial repair; gain of function; gastrointestinal epithelium; genetic regulatory protein; improved; innovation; intestinal epithelium; laboratory development; medical schools; microorganism; migration; military veteran; novel; novel therapeutics; operation; patient population; posttranscriptional; preservation; professor; programs; receptor; repaired; research and development; response; restoration; self-renewal; systems research; therapeutically effective

AIMS: The goal of this application is to competitively renew Dr. Jian-Ying Wang's Senior Research Career Scientist (SRCS) Award, and to continuously support Dr. Wang's VA research program. NOMINEE: Dr. Wang has held a position of Senior Research Career Scientist from 2011, and he also holds the title of Professor in the Departments of Surgery and Pathology at University of Maryland School of Medicine (UMSOM) at Baltimore. Dr. Wang's research program has been continuously funded by VA- MERIT Review Awards and multiple NIH-R01 grants for more than twenty-two years. Dr. Wang has had many seminal research accomplishments throughout his career, and published more than 140 peer- reviewed original research articles that have created more than 5,000 citations. In addition, Dr. Wang is a major mentor/sponsor for VA Career Development Awards, and he also acts as a co-investigator in several currently active VA-sponsored research projects. RESEARCH: Studies in Dr. Wang's laboratory are to investigate the mechanisms underlying gut mucosal regeneration and rapid epithelial restitution after acute injury; and to further search for new and more effective therapies to maintain the intestinal epithelial integrity in patients with critical illness. Defective regulation of early intestinal mucosal restitution and subsequent disruption of the gut epithelial integrity occur commonly in various pathological states such as: stress/peptic ulcerations, Crohn's disease/ulcerative colitis, post-massive surgery, trauma, and sepsis. Since the exact mechanisms underlying gut mucosal continuous regeneration and rapid mucosal repairs after acute injury are still obscure; effective therapies to preserve the gut epithelial integrity are limited, especially in patients with critical surgical illnesses. Dr. Wang's research program is highly focused on the regulation of rapid gut mucosal repair and homeostasis by Ribonucleic acid ( RNA)-binding proteins (RBPs) and noncoding RNAs (ncRNAs) in health and surgical diseases. His research program studies stress-related processes regulated by RBPs and ncRNAs, the post-translational events that affect target gene expression in the presence or absence of cellular polyamines, and the interplay between RBPs and ncRNAs under physiological and pathological conditions. Dr. Wang's research employs the state-of-the-art techniques, including approaches that examine specific messenger (m)RNA/ncRNA or mRNA/RBP interactions as well as approaches focused on large-scale RNA analyses. His group has also extensively used gain-of- function transgenic and tissue-specific knockout approaches to generate various genetically modified animal models. Importantly, Dr. Wang's research projects are directly relevant to surgical patients with mucosal injury/delayed healing, maladaptation, barrier dysfunction, inflammation, and sepsis. The overarching goal of Dr. Wang's research program is to elucidate the post-transcriptional processes that govern gut mucosal regeneration and rapid epithelial restitution, and to create a fundamental base for development of new therapeutics for gut mucosal injury-related diseases. IMPACT: Dr. Wang's research program directly addresses an important health issue relevant to the VA mission, since gut mucosal injury-related diseases such as stress/peptic ulcerations, Crohn's disease/ulcerative colitis, and gut barrier dysfunction occur commonly in our VA patient population. Dr. Wang also actively collaborates with a number of investigators in the VA Maryland Health Care System (VAMHCS) Research Service, and his expertise and academic activity help moving the VAMHCS research program forward.

目的：本申请的目的是竞争性地更新王建英博士的高级研究 职业科学家（SRCS）奖，并继续支持王博士的VA研究计划。 提名：王博士自2011年起担任高级研究职业科学家， 马里兰州大学医学院外科和病理学系教授 医学（UMSOM）在巴尔的摩。王博士的研究项目一直由VA资助- MERIT评审奖和多个NIH-R 01赠款超过二十二年。王医生有 在他的职业生涯中取得了许多开创性的研究成果，并发表了140多篇同行论文， 审查了被引用超过5,000次的原创研究文章。此外，王博士还是一名 他是VA职业发展奖的主要导师/赞助商，他还在几个项目中担任联合调查员。 目前正在进行的研究项目。 研究：王博士实验室的研究是调查肠道粘膜的潜在机制， 再生和快速上皮修复急性损伤后，并进一步寻找新的和更多的 维持危重病患者肠上皮完整性的有效疗法。缺陷 调节早期肠粘膜恢复和随后的肠上皮完整性破坏 常见于各种病理状态，例如：应激/消化性溃疡、克罗恩病 疾病/溃疡性结肠炎、大手术后、创伤和败血症。因为确切的机制 急性损伤后潜在的肠粘膜持续再生和快速粘膜修复仍然是 不明确;保护肠道上皮完整性的有效疗法有限，特别是在患有 严重的外科疾病。王博士的研究项目高度集中在快速肠道的调节， 通过核糖核酸（RNA）结合蛋白（RBP）和非编码蛋白进行粘膜修复和体内平衡 RNA（ncRNA）在健康和外科疾病中的作用他的研究项目研究与压力有关的过程 由RBP和ncRNA调节，影响靶基因表达的翻译后事件， 细胞多胺的存在或不存在，以及RBP和ncRNA之间的相互作用， 生理和病理条件。王博士的研究采用了最先进的技术， 包括检测特定信使（m）RNA/ncRNA或mRNA/RBP相互作用的方法 因为这些方法集中在大规模的RNA分析上。他的团队还广泛使用了增益- 功能转基因和组织特异性敲除方法，以产生各种遗传修饰的 动物模型重要的是，王博士的研究项目直接与手术患者相关， 粘膜损伤/延迟愈合、适应不良、屏障功能障碍、炎症和脓毒症。的 王博士的研究计划的首要目标是阐明转录后过程， 控制肠粘膜再生和快速上皮恢复，并为 开发用于肠粘膜损伤相关疾病的新疗法。 影响：王博士的研究项目直接解决了与VA相关的重要健康问题 使命，因为肠粘膜损伤相关的疾病，如应激/消化性溃疡，克罗恩病 疾病/溃疡性结肠炎和肠道屏障功能障碍通常发生在我们的VA患者人群中。博士 王还积极与弗吉尼亚州马里兰州卫生保健系统的一些调查人员合作 （VAMHCS）研究服务，他的专业知识和学术活动有助于推动VAMHCS研究 节目向前。