Cellular and Molecular Mechanisms of Acute Lung Injury in Sickle Cell Disease

镰状细胞病急性肺损伤的细胞和分子机制

• 批准号: 8468275
• 负责人: Michael R. DeBaun
• 金额: $ 189.75万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8468275
• 关键词: Acute Lung Injury; Awareness; Biological Markers; Biomedical Research; Cause of Death; Clinical Data; Clinical Research; Clinical Trials Design; Communities; Development; Doctor of Philosophy; Foundations; Functional disorder; Genetic Markers; Genetic Polymorphism; Genomics; Health; Hematology; Heme; Hemoglobinopathies; Hemolysis; Human; Human Resources Development; Incidence; Individual; Link; Lung; Mentors; Minority; Molecular; Morehouse School of Medicine; Mus; Phase I Clinical Trials; Physicians; Positioning Attribute; Research; Research Personnel; Research Project Grants; Research Training; Role; Scientist; Severities; Sickle Cell; Sickle Cell Anemia; Solid; Students; Testing; Therapeutic; Tissues; Training; Training Programs; Translational Research; abstracting; acute chest syndrome; career; career development; design; drug candidate; experience; heme a; high school; improved; inhibitor/antagonist; lung injury; novel; novel therapeutic intervention; novel therapeutics; pre-clinical; prevent; programs; research study; skills; toll-like receptor 4

DESCRIPTION (provided by applicant): The Emory Center of Excellence in Hemoglobinopathy Research (CEHR) aspires to improve the health of individuals with sickle cell disease (SCD) by developing novel therapeutics and biomarkers for the major cause of death in SCD acute chest syndrome (ACS), through the discovery of critical molecular and cellular mechanisms, and genetic markers of human diversity that influence ACS, and to build capacity in our community in translational research, awareness and career pipelines in biomedical research. Our overarching scientific hypothesis is that heme, a product of tissue damage and hemolysis induces ACS via interaction with toll-like receptor 4 (TLR4). The Emory CEHR assembles a multi-disciplinary team of geneticists, hematology physicians and scientists, and lung biologists to rigorously test this hypothesis and explore its therapeutic potential in three inter-related Specific Aims: [1] Define cellular and molecular mechanisms, and inhibitors of heme-induced endothelial dysfunction and lung injury. [2] Determine the role of TLR4 in the development of ACS in SCD mice and generate pre-clinical data for novel therapeutics. [3] Identify genetic polymorphisms associated with the incidence and severity of ACS. A Translational Research Skills Development Core aims to train an MD and a PhD scientist in clinical research and provide mentored research experience for them to become independent investigators. Training for the MD scholar will emphasize phase I clinical trial design, execution and analysis, and the scholar will participate in the design of a Phase I trial of candidate drug(s) emerging from the research project. The PhD scholar, pursuing training in clinical research and genomics, will also be positioned to participate in the research studies of the CEHR. The Sickle Cell Summer Research Training Program for high school students links with a robust program of career development for minority students at Morehouse School of Medicine. In summary, the proposed project of the Emory CEHR will rigorously test a novel mechanism of lung injury, identify candidate drugs that interfere with it, and lay a solid foundation - in both scientific and human resources - for the development of an entirely new therapeutic approach to preventing or treating ACS in sickle cell disease. (End of Abstract)

描述（由申请人提供）：