The role of coagulation cascade proteases in pleural fibrosis

凝血级联蛋白酶在胸膜纤维化中的作用

• 批准号: 8367874
• 负责人: Torry Alle Tucker
• 金额: $ 11.02万
• 依托单位: UNIVERSITY OF TEXAS HLTH CTR AT TYLER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8367874
• 关键词: Acute; Address; Advisory Committees; Affect; Anesthesia procedures; Antithrombin III; Apoptosis; Area; Attenuated; Biochemistry; Biological Markers; Biomedical Research; Bleomycin; Carbon Black; Cell Survival; Cellular biology; Characteristics; Chemicals; Cicatrix; Coagulation Process; Collagen; Data; Deposition; Development; Disease; Ensure; Environment; Excision; Exhibits; Factor Xa; Faculty; Fibrin; Fibrinolysis; Fibrinolytic Agents; Fibrosis; Health Sciences; Hemorrhage; Hirudin; Hirudins; Human; Immunologics; In Vitro; Injury; Laboratories; Light; Link; Lung; Mediating; Mentors; Mentorship; Mesenchymal; Mesothelial Cell; Mesothelium; Modeling; Molecular; Molecular Biology Techniques; Mus; Operative Surgical Procedures; Pathogenesis; Pathway interactions; Patients; Peptide Hydrolases; Phenotype; Phosphorylation; Plasminogen Activator Inhibitor 1; Pleura; Pleural; Pleural Mesothelial Cell; Postdoctoral Fellow; Principal Investigator; Process; Protein Chemistry; Proteinase-Activated Receptors; Proteins; Publications; Reporting; Research; Research Personnel; Research Project Grants; Resistance; Risk; Role; Signal Pathway; Signal Transduction; Sirolimus; Smooth Muscle Actin Staining Method; TFPI; Techniques; Texas; Thrombin; Tight Junctions; Tissues; Training Programs; Universities; Work; abstracting; base; career; cell motility; design; human FRAP1 protein; in vivo; inhibitor/antagonist; interest; mTOR Inhibitor; mouse model; new therapeutic target; novel; professor; programs; repaired; response

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program designed to facilitate the ability of the candidate to pursue an independent career in the field of pleural fibrosis. The candidate came to The University of Texas Health Science Center at Tyler as a post-doctoral fellow, has joined the faculty as an Assistant Professor of Biochemistry and will continue his transition to independence through comprehensive mentorship and by conducting a completely novel, high impact scientific project. This program will shed new light on the pathogenesis of pleural fibrosis, which affects thousands of patients annually and for which treatment options are invasive or of uncertain benefit. In work reported by this laboratory, the mesothelium has previously been shown to promote fibrotic repair by promoting local procoagulant activity and suppressing fibrinolysis in the pleural compartment. The mesothelium can also support pleural organization and unrestricted repair via phenotypic changes of mesothelial cells; mesomesenchymal transition (MT). Our preliminary data support the concept that procoagulants induce MT. The role of factor Xa and thrombin in MT is now unknown and will be elucidated in this project. Dr. Steven Idell will serve as the primary mentor for the principal investigator's scientific development. Dr. Idell is a leader in the field of coagulation nd fibrinolysis in lung and pleural injury who has a long-standing interest in the treatment of pleura fibrosis. He is the Vice President for Research at The University of Texas Health Science Center at Tyler (UTHSCT) and has mentored numerous successful trainees. An advisory committee including Dr. Hua Tang and Dr. Sreerama Shetty resident experts in the field of lung fibrosis and Dr. L. Vijaya Rao a world renowned expert in the field of coagulation will mentor the applicant. They will ensure that the applicant achieves his objective of becoming a successful independent investigator. Our hypothesis is that factor Xa and thrombin are important determinants of MT and pleural fibrosis. Our objective is to elucidate the contribution of coagulation proteases to MT and the development of pleural loculation and fibrosis that follow acute pleural injury. The Specific Aims of the proposal are: 1) to determine the mechanism of FXa and thrombin mediated MT in pleural mesothelial cells, 2) to elucidate the role of Akt and Wnt/¿-catenin-signaling in FXa and thrombin mediated-MT in PMCs, and 3) to determine the role of FXa and thrombin in evolving fibrosing pleural injury in mice. To accomplish this work, a number of techniques, including cell biology, immunologic, protein chemistry and molecular biology techniques will be used. The Biomedical Research Department of UTHSCT is an ideal setting to conduct this research project. The combination of strong institutional support and an enthusiastic, productive advisory committee provides a nurturing environment that will enable the applicant to accelerate his successful transition to an independent investigative career. (End of Abstract)

描述（由申请人提供）：此提案描述了一个为期5年的培训计划，旨在促进候选人在专业领域追求独立职业的能力