Patient-Oriented Research in Beryllium-Induced Disease

以患者为导向的铍诱发疾病研究

• 批准号: 7869189
• 负责人: Andrew P. Fontenot
• 金额: $ 15.29万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7869189
• 关键词: Accounting; Alanine; Alleles; Alveolitis; Amino Acids; Antigen-Presenting Cells; Antigens; Attention; Award; Berylliosis; Beryllium; Binding; Binding Sites; Biological; Biological Markers; Blood; Bronchoalveolar Lavage; CD4 Positive T Lymphocytes; Chemicals; Chronic berylliosis; Clinical; Clinical Sciences; Clonal Expansion; Collaborations; Colorado; Complement; Complementarity Determining Regions; Complex; Data; Dengue; Dengue Virus; Development; Disease; Disease Progression; Disease susceptibility; Dissection; Educational process of instructing; Ensure; Epitopes; Faculty; Fibroblasts; Frequencies; Functional disorder; Funding; Genetic Predisposition to Disease; Glutamic Acid; Goals; Granulomatous; HLA-DP Antigens; HLA-DP2; Health; Human; Hybridomas; Immune; Immune response; Immunology; Industry; Inflammation; Institutes; Interleukin-2; Lead; Ligands; Link; Lung; Lung diseases; Mediating; Mentored Clinical Scientist Development Program; Mentors; Metals; Methionine; Modality; Modeling; Mus; Mutate; Mutation; Occupational; Organ; Patients; Peptide Library; Peptides; Physicians; Play; Population; Positioning Attribute; Pulmonology; Quality of life; Research; Research Infrastructure; Research Support; Research Training; Resources; Rest; Role; Scientist; Severities; Site-Directed Mutagenesis; Social Welfare; Specimen; Staining method; Stains; Structure; Surface Antigens; T memory cell; T-Cell Activation; T-Lymphocyte; Technology; Therapeutic; Time; Training; Translating; Translational Research; Universities; Vertebral column; Viral; Workplace; base; carboxylate; career; career development; cell type; cytokine; disorder risk; electron donor; follower of religion Jewish; high risk; human subject; improved; memory CD4 T lymphocyte; next generation; patient oriented research; patient population; physical property; programs; tool; translational study

DESCRIPTION (provided by applicant): The overall goal of this proposed mid-career award is to enhance Dr. Fontenot's ability to train, mentor and support the career development of fellows, junior faculty and other trainees in patient-oriented research in granulomatous lung disease, in particular beryllium-induced disease. This proposal will insure that Dr. Fontenot has adequate protected time to provide more opportunities for teaching and mentoring fellows, junior faculty and other trainees. In addition, this protected time will allow Dr. Fontenot to participate in coursework that will enhance his ability translate his findings toward improving the quality of life of subjects with beryllium-induced disease. Chronic beryllium disease (CBD) is an occupational lung disease that is characterized by granulomatous inflammation and a CD4+ T cell alveolitis. Due to its unique chemical and physical properties, beryllium continues to be utilized in high-technology industries, with more than 1,000,000 US workers having been exposed to beryllium and at risk for disease development. With the presence of a known antigen and an accessible target organ, CBD is an important model of immune-mediated, organ destruction. We and others have shown the importance of HLA-DP2 in the genetic susceptibility of CBD and in the presentation of beryllium to pathogenic CD4+ T cells. Using blood and bronchoalveolar lavage from human subjects, the goals of the research plan are to elucidate the mechanism by which beryllium-specific CD4+ T cells recognize beryllium in the context of HLA-DP2 and to demonstrate the stability of the beryllium-specific memory T cell pool. Findings from these studies may identify potential biomarkers of disease progression in high-risk subjects as well as therapeutic modalities that block beryllium binding to HLA-DP2 molecules on the surface of antigen presenting cells. This program builds on Dr. Fontenot's recently renewed R01 investigating the role of pathogenic T cells in beryllium-induced disease. The mentoring plan will expand Dr. Fontenot's role in mentoring physician-scientists and other trainees in patient-oriented research. In addition, the research and mentoring plan will leverage the resources and infrastructure present at the University of Colorado and National Jewish Health, including the Clinical Science Program and K12 Program in the Colorado Clinical and Translational Sciences Institute, an outstanding Pulmonary Division with a long track record for successfully training physician-scientists, and long-standing collaborations that bridge basic immunology and patient oriented research, to improve the quality of life of CBD patients. With the support of this award, Dr. Fontenot will become a leader in translational lung immunology research and train the next generation of physician scientists in pulmonary medicine.

描述（由申请人提供）：这项拟议的职业中期奖励的总体目标是提高博士Fontenot的能力，以培训，指导和支持研究员，初级教师和其他学员的职业发展，在肉芽肿性肺病，特别是铍诱导的疾病的患者为导向的研究。这项建议将确保Fontenot博士有足够的保护时间，为教学和指导研究员、初级教员和其他受训人员提供更多的机会。此外，这一受保护的时间将使Fontenot博士能够参加课程，这将提高他的能力，将他的发现转化为改善铍诱导疾病受试者的生活质量。慢性铍病（CBD）是一种以肉芽肿性炎症和CD 4 + T细胞肺泡炎为特征的职业性肺病。由于其独特的化学和物理性质，铍继续用于高科技行业，超过1，000，000名美国工人暴露于铍并面临疾病发展的风险。由于存在已知抗原和可接近的靶器官，CBD是免疫介导的器官破坏的重要模型。我们和其他人已经证明了HLA-DP 2在CBD遗传易感性和铍对致病性CD 4 + T细胞的呈递中的重要性。使用人类受试者的血液和支气管肺泡灌洗，研究计划的目标是阐明铍特异性CD 4 + T细胞在HLA-DP 2背景下识别铍的机制，并证明铍特异性记忆T细胞库的稳定性。这些研究的结果可以确定高危受试者疾病进展的潜在生物标志物，以及阻断铍与抗原呈递细胞表面HLA-DP 2分子结合的治疗方式。该计划建立在Fontenot博士最近更新的R 01研究中，该研究调查了病原性T细胞在铍诱导疾病中的作用。指导计划将扩大Fontenot博士在指导医生科学家和其他学员进行以病人为导向的研究方面的作用。此外，研究和指导计划将利用科罗拉多大学和国家犹太健康中心的资源和基础设施，包括科罗拉多临床和转化科学研究所的临床科学项目和K12项目，该研究所是一个杰出的肺科，在成功培训医生科学家方面有着悠久的历史，长期合作，将基础免疫学和以患者为导向的研究联系起来，以提高CBD患者的生活质量。在该奖项的支持下，Fontenot博士将成为转化肺免疫学研究的领导者，并培养下一代内科医生科学家 在肺内科。