BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 9899092
• 负责人: MACK H WU
• 金额: --
• 依托单位: JAMES A. HALEY 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9899092
• 关键词: 3-Dimensional; Achievement; Adherens Junction; Adult Respiratory Distress Syndrome; Aging; American; Area; Arteriovenous fistula; Atherosclerosis; Award; Bacteria; Bacterial Translocation; Basement membrane; Blood; Blood Vessels; Blood specimen; Burn injury; Cell-Cell Adhesion; Cells; Chemical Burns; Chronic; Clinical; Collaborations; Complex; Critical Care; Data; Development; Diabetes Mellitus; Disease; Disseminated Malignant Neoplasm; Dissociation; Endothelium; Epithelial; Epithelium; Evaluation; Experimental Models; Extravasation; Failure; Focal Adhesion Kinase 1; Focal Adhesions; Functional disorder; Glean; Goals; Hospital Charges; Image; Impairment; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Injury; Intercellular Junctions; Intervention; Intestinal permeability; Intestines; Ischemia; Knockout Mice; Lead; Leaky Gut; Length of Stay; Life; Literature; Matrix Metalloproteinases; Mediating; Mediator of activation protein; Medical; Medicine; Molecular; Molecular Genetics; Morbidity - disease rate; Mucous Membrane; Multiple Organ Failure; Obesity; Operative Surgical Procedures; Organ; Pathogenesis; Pathway interactions; Patients; Permeability; Phase; Physiological; Plasma; Play; Population; Property; Protein Isoforms; Regulation; Reporting; Research; Research Design; Research Personnel; Role; Scientist; Sepsis; Signal Transduction; Site; Soldier; Structure; Superoxide Dismutase; Surgeon; Syndrome; Techniques; Testing; Therapeutic; Tight Junctions; Tissues; Toxin; Trauma; Vascular Diseases; Vascular remodeling; Veterans; Work; Writing; base; career; chronic wound; clinically relevant; combat; effective therapy; experimental study; fluorescence imaging; gastrointestinal; gastrointestinal epithelium; genetic approach; heat injury; improved; in vitro Model; in vivo; insight; intestinal barrier; intestinal epithelium; monocyte; mortality; novel; outcome forecast; predict clinical outcome; programs; response; restenosis; success; transcription factor; wound care; wound healing; wound treatment

The overall objective of this application is to expand my current project towards a new phase to further investigate the molecular control of cell specific mechanisms that contribute to the diseases that are commonly in American Veterans. The future research focuses on the role of focal adhesion kinase (FAK) in the regulation of gut barrier injury during trauma. Additional efforts will be devoted in collaboration with VA surgeons to examining molecular mechanisms of endothelial barrier dysfunction and MMP dysregulation that lead to the failure of vascular remodeling in VA patients. Trauma-induced inflammation and multiple organ failure are major causes of mortality and morbidity in American soldiers and veterans. Gut barrier dysfunction plays a critical role in the development of posttraumatic complications by providing the major site for plasma leakage and bacterial translocation. The intestinal epithelial barrier damage in burns, a major form of trauma, has not been well characterized clinically. In addition, its cellular and molecular mechanisms remain incompletely understood. The major goal of application is to elucidate the cell-specific mechanisms of leaky guts during thermal injury. We hypothesize that thermal injury induced inflammation in gut tissue activates Src and FAK activity in intestinal epithelium, stimulate focal remodeling and ZO1 mediated junction disassociation therefore impairing gut epithelial barrier integrity. The specific goals developed in this study are: 1) to analyze the molecular mechanism of FAK mediated gut epithelial barrier dysfunction, and 2) to evaluate the functional role of FAK activation and therapeutic potential of FAK inhibition in gut barrier dysfunction during thermal injury. The study design employs complimentary in vivo, ex vivo, and in vitro models that incorporate molecular and genetic approaches into physiological experiments under clinically relevant trauma conditions. The significance of the study lies in its potential to establish a new molecular pathway in the regulation of tight and adherens junctions. Information gleaned from the research work will not only contribute to the advancement of gastrointestinal pathobiology, but also has clinical implications in the development of effective therapies or surgical interventions against gut barrier injury in the VA patients with trauma and inflammatory bowel diseases.

这个应用程序的总体目标是将我当前的项目扩展到一个新的阶段