Program for Patient-Oriented Environment Health Research and Training

描述(由申请人提供) 这一竞争更新的K24职业生涯中期研究人员奖的总体目标是在最初的K24奖期间取得实质性进展的基础上，加强耶鲁大学专注于环境健康的临床多学科研究的培训。候选人Carrie A.Redlich，医学博士，公共卫生硕士，是一位备受尊敬的多产临床研究员，在多学科环境/职业健康研究方面拥有独特的培训和研究经验。这项建议将使雷德利希博士能够扩大她目前专注于了解异氰酸酯暴露对健康影响的研究工作，提高她自己的研究技能，并极大地推进她的导师计划。该研究计划包括目前支持的多学科研究，调查接触六亚甲基二异氰酸酯(HDI)对汽车车身修理厂工人的影响、风险因素、机械途径和预防方法。该K24奖项特别支持的新研究将集中于二苯基甲烷二异氰酸酯(MDI)，这是全球最常用的异氰酸酯。它建立在迄今为止的实质性进展和与Uretek的长期关系基础上，Uretek是一家位于纽黑文的织物涂层公司，在生产聚氨酯涂层织物时使用MDI，并将解决与MDI的生物相关抗原形式、皮肤暴露的作用、暴露剂量关系和宿主因素有关的重要问题。具体目标是： 目的1)鉴定和鉴定与生物相关的MDI抗原型。 目的2)评估乌雷泰克个体工人的呼吸和健康状况。 目的3)描述Uretek的个人MDI皮肤和呼吸道暴露模式。 目的利用DNA芯片和蛋白质组学分析方法，研究MDI暴露对基因和蛋白质表达谱的影响。 目的5)将暴露、临床、免疫学、生理学和人口学数据与基因组和蛋白质组数据相结合，以探索影响暴露风险的暴露疾病关联和宿主易感因素。重要的是，这个新项目还将有助于提高雷德利希博士在新领域的研究技能，并提供一个指导朱尼尔的独特机会。

DESCRIPTION (provided by applicant) The overarching goal of this competing renewal K24 Mid-Career Investigator Award in Patient-Oriented Research is to enhance training in clinical multidisciplinary research focused on environmental health at Yale, building upon the substantial progress made during the initial K24 award. The candidate, Carrie A. Redlich, MD, MPH, is a highly respected and productive clinical investigator with unique training and research experience in multidisciplinary environmental/occupational health research. This proposal will enable Dr. Redlich to expand her current research efforts focused on understanding the health effects of isocyanate exposures, enhance her own research skills, and greatly advance her mentorship program. The research plan includes currently supported multidisciplinary studies investigating the effects of exposure to hexamethylene diisocyanate (HDI) in auto body shop workers, risk factors, mechanistic pathways and preventive approaches. New research specifically supported by this K24 award will focus on diphenylmethane diisocyanate (MDI), the most commonly used isocyanate worldwide. It builds upon the substantial progress to date and a long-standing relationship with Uretek, a fabric coating company in New Haven that uses MDI in the production of polyurethane coating fabrics, and will address important questions concerning the biologically relevant antigenic form of MDI, the role of skin exposure, exposure-dose relationships, and host factors. The specific aims are: AIM 1) Identify and characterize biologically relevant antigenic forms of MDI. AIM 2) Evaluate the respiratory and health status of individual workers at Uretek. AIM 3) Characterize individual MDI skin and respiratory exposure patterns at Uretek. AIM 4) Characterize the effects of MDI exposure on gene and protein expression profiles using DNA microarray and proteomic analyses. AIM 5) Integrate exposure, clinical, immunologic, physiologic, and demographic data with genomic and proteomic data to explore exposure disease associations and host susceptibility factors which modify risks of exposure. Importantly, this new project will also serve to advance Dr. Redlich's research skills in new areas and provide a unique opportunity to mentor junior.