Trauma induced endothelial cell Ca2+ signaling

创伤诱导的内皮细胞 Ca2 信号传导

• 批准号: 9926566
• 负责人: Daniel Mohr Collier
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926566
• 关键词: Address; Affect; Animal Model; Antibodies; Arteries; Biochemistry; Biology; Biophysics; Blood; Blood Circulation; Blood Coagulation Disorders; Blood Vessels; Blood flow; Calcium Signaling; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cell physiology; Cells; Cerebrum; Clinical; Coagulation Process; Complement; Cyclic GMP-Dependent Protein Kinases; Cytolysis; Data; Development; Doctor of Medicine; Doctor of Philosophy; Edema; Electrophysiology (science); Endothelial Cells; Endothelium; Environment; Event; Functional disorder; Gap Junctions; Histones; Hospitals; Hypertension; Hypotension; Image; Image Analysis; Imaging Techniques; Inflammatory; Injury; Inositol; Institution; International; Ion Channel; Iowa; Knowledge; Laboratories; Liquid substance; Measures; Mechanics; Mentors; Mentorship; Mesenteric Arteries; Modeling; Molecular; Molecular Biology; Myography; Nitric Oxide; Optics; Pattern; Percussion; Pharmacology; Phosphorylation; Physiological; Physiology; Postdoctoral Fellow; Process; Production; Proteins; Public Health; Pulsar; Regulation; Research; Research Personnel; Research Support; Resistance; Role; Signal Pathway; Signal Transduction; Stream; Stroke; Structure; Survivors; Techniques; Time; Tissues; Training; Trauma; Trauma patient; Traumatic Brain Injury; Traumatic injury; Universities; Vanilloid; Vascular Diseases; Vascular Endothelium; Vascular Permeabilities; Vermont; Visit; career; cerebral artery; clinical care; cost; effective therapy; experience; extracellular; gain of function; graduate student; imaging approach; improved; inorganic phosphate; insight; intercellular communication; mouse model; neutrophil; novel; preservation; pressure; prevent; programs; ratiometric; receptor; skills

This proposal describes a 5-year program (2 years mentored, 3 years independent) for the development of an academic career in cardiovascular disease and trauma pathophysiology research with an emphasis on ion channel function and Ca2+ signaling pathways. Dr. Collier (the applicant) has a background in ion channel structure and function, biochemistry, and molecular biology. He competed his doctoral training in the Department of Molecular Physiology & Biophysics at the University of Iowa under the mentorship of Dr. Peter Snyder. He came to the University of Vermont as Postdoctoral Associate to develop new skills in Ca2+ imaging, vascular biology, and animal models of traumatic injury to aid his transition toward becoming an independent investigator. The University of Vermont (UVM) is internationally recognized for its strength in pharmacology, with unique expertise in Ca2+ signaling, vascular biology, and trauma. Mark Nelson, Ph.D. will mentor Dr. Collier's scientific development and transition to independence. Dr. Nelson is a recognized leader in the field of Ca2+ signaling and vascular biology. Dr. Nelson has trained numerous postdoctoral fellows and graduate students, many of whom are now established independent investigators. Kalev Freeman, M.D., Ph.D. will co-mentor Dr. Collier. Dr. Freeman provides unique clinical perspective and expertise in trauma pathophysiology. This research environment maximizes the potential for Dr. Collier to establish a scientific niche from which an academic career can be constructed. This project will facilitate continued technical, intellectual, and professional training which will help Dr. Collier develop a unique skill set that will allow him to establish an independent laboratory at an academic research institution of his choosing. Traumatic injury is a major public health problem. Trauma accounts for 37 million hospital visits and is estimated to cost the U.S. more than $700 billion each year. Traumatic brain injury (TBI) accounts for 1.7 million hospital visits and often leaves survivors suffering from cardiovascular complications such as hypertension, hypotension, coagulopathy, and stroke. The mechanism of these systemic complications is unknown. It has been demonstrated that traumatic injury releases toxic intracellular components into the systemic circulation, however, little is known about how these toxic factors affect tissue at the molecular level. This project will elucidate the basis of persistent altered endothelial cell function in systemic arteries following TBI, the mechanism by which trauma associated circulating factors induced endothelial cell Ca2+ signaling, and the basis of preservation of cerebral artery function following TBI.

该提案描述了一个5年的计划（2年指导，3年独立）