Patient-Oriented Research in Beryllium-Induced Disease

以患者为导向的铍诱发疾病研究

基本信息

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
项目类别：
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

项目摘要

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）：该拟议职业生涯中期奖项的总体目标是增强 Fontenot 博士培训、指导和支持研究员、初级教师和其他受训人员在以患者为导向的肉芽肿性肺病研究中的职业发展的能力，特别是铍引起的疾病。该提案将确保丰特诺博士有足够的受保护时间，为教学和指导研究员、初级教师和其他学员提供更多机会。此外，这段受保护的时间将使 Fontenot 博士能够参加课程作业，从而提高他的能力，将他的发现转化为改善铍诱发疾病受试者的生活质量。慢性铍病 (CBD) 是一种职业性肺部疾病，其特征是肉芽肿性炎症和 CD4+ T 细胞肺泡炎。由于其独特的化学和物理特性，铍继续被用于高科技行业，超过 1,000,000 名美国工人曾接触铍并面临罹患疾病的风险。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-DP2 在 CBD 遗传易感性和铍向致病性 CD4+ T 细胞呈递中的重要性。该研究计划利用人类受试者的血液和支气管肺泡灌洗液，阐明铍特异性 CD4+ T 细胞在 HLA-DP2 背景下识别铍的机制，并证明铍特异性记忆 T 细胞的稳定性水池。这些研究的结果可能会确定高危受试者疾病进展的潜在生物标志物，以及阻止铍与抗原呈递细胞表面的 HLA-DP2 分子结合的治疗方式。该项目以 Fontenot 博士最近更新的 R01 为基础，研究致病性 T 细胞在铍诱发疾病中的作用。该指导计划将扩大丰特诺博士在指导医师科学家和其他受训人员以患者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现有的资源和基础设施，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，该研究所是一个长期发展的杰出肺科部门。成功培训医生科学家的记录，以及在基础免疫学和以患者为导向的研究之间建立长期合作的桥梁，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，并培养下一代肺医学领域的医师科学家。