Program for Patient-Oriented Environment Health Research and Training

描述（由申请人提供） 这个竞争性的更新K24中期职业研究者奖以患者为导向的研究的总体目标是加强在耶鲁大学的环境健康为重点的临床多学科研究的培训，在最初的K24奖取得的实质性进展的基础上。 候选人Carrie A. Redlich，医学博士，公共卫生硕士，是一位备受尊敬和富有成效的临床研究者，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。 这一提议将使Redlich博士能够扩大她目前的研究工作，重点是了解异氰酸酯暴露对健康的影响，提高她自己的研究技能，并大大推进她的导师计划。 该研究计划包括目前支持的多学科研究，调查汽车车身车间工人暴露于HDI的影响，风险因素，机械途径和预防方法。 K24奖特别支持的新研究将集中在二苯基甲烷二异氰酸酯（MDI）上，这是全球最常用的异氰酸酯。 它建立在迄今取得的重大进展和与纽黑文的一家织物涂层公司Uretek的长期关系的基础上，该公司在聚氨酯涂层织物的生产中使用MDI，并将解决有关MDI的生物相关抗原形式、皮肤接触的作用、剂量-剂量关系和宿主因素的重要问题。 具体目标是： 目的1）鉴定和表征MDI的生物学相关抗原形式。 目的2）评价优瑞泰克个体工人的呼吸和健康状况。 目的3）描述Uretek的个体MDI皮肤和呼吸暴露模式。 目的4）利用基因芯片和蛋白质组学技术研究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、生理学和人口统计学数据与基因组和蛋白质组学数据相结合，以探索暴露疾病相关性和改变暴露风险的宿主易感性因素。 重要的是，这个新项目还将有助于提高雷德利奇博士在新领域的研究技能，并提供一个独特的机会，指导初级。

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.