The Impact of Zinc on Innate Immunity and Patient Safety in Sepsis

简介（由申请人提供）：候选人：Beth Y. Besecker，医学博士，俄亥俄州立大学肺科和重症监护科助理教授。Besecker博士最初的基础科学研究评估了锌在肺上皮细胞中的细胞保护作用。最近，她参与了一项转化研究，评估锌在脓毒症细菌吞噬和清除中的作用。Besecker博士利用体外和小鼠体内模型进行与锌相关的吞噬研究。她还进行了两项观察性研究，评估锌与重症败血症患者疾病严重程度和死亡率的关系。Besecker博士的短期目标是获得免疫生物学特异性先天免疫/细菌清除和临床研究设计和实施方面的培训，使她能够过渡到锌免疫生物学和败血症领域的独立转化研究员。长期目标是开发和领导一个转化的多中心研究项目，专注于优化营养，以改善危重患者的预后。K23导师职业发展奖的支持将为实现这些目标提供基础。职业发展：Dr. Besecker的职业发展/培训将涵盖4个核心领域，包括：1)实验室技术-流式细胞术和动物手术；2)介入性临床试验的设计与管理；3)项目管理/研究项目组织；核心知识-免疫生物学、药理学和生物统计学。还将通过与指导者小组成员的互动和参加当地和国际会议来加强培训。环境：Dr. Besecker的环境有利于优秀的研究。她得到了五位杰出的R01资助研究人员的科学支持，他们都有指导经验，包括导师Larry Schlesinger博士和联合导师Susan Koletar博士。贝塞克博士从她的研究所、部门、导师那里获得了经济支持，目前是一名高级管理人员

DESCRIPTION (provided by applicant): Candidate: Beth Y. Besecker, M.D. is an Assistant Professor in the Pulmonary and Critical Care Division at The Ohio State University. Dr. Besecker's initial basic science research evaluated zinc's cytoprotective role in lung epithelia. Recently she has been involved in translational research evaluating the role of zinc in bacterial phagocytosis and clearance in sepsis. Dr. Besecker utilizes both an in vitro and murine in vivo model for her zinc-related phagocytosis studies. She has also conducted two observational studies evaluating zinc's relation to the severity of illness and mortality in critically ill septi patients. Dr. Besecker's short term goal is to obtain training in both immunobiology specific to innate immunity/ bacterial clearance and clinical research design and implementation to allow her to transition to an independent translational researcher in the areas of zinc immunobiology and sepsis. A longer term goal is to develop and lead a translational, multi-center research program that focuses on optimizing nutrition to improve patient outcomes in the critically ill. Support from a K23 Mentored Career Development Award would provide the foundation to attain these goals. Career Development: Dr. Besecker's career development/ training will cover 4 Core Areas and include: 1) Laboratory techniques- flow cytometry and animal surgery; 2) Design and management of interventional clinical trials; 3) Project Management/ Organization of Research Programs; 4) Core Knowledge- immunobiology, pharmacology, and biostatistics. Training will also be enhanced by interaction with mentor team members and participation in local and international meetings. Environment: Dr. Besecker's environment is conducive to excellent research. She has the scientific support of five exceptional R01 funded investigators with mentoring experience including Mentor, Dr. Larry Schlesinger and Co-mentor, Dr. Susan Koletar. Dr. Besecker has financial support from her institute, division, mentors, and currently an NIH-funded OSU Center for Clinical and Translation Sciences KL2 award. Research: Sepsis, a systemic inflammatory response to infection, kills over 215,000 patients and costs 16 billion dollars annually. Zinc has immune regulatory and cell protective properties and may be an important therapy for improved survival in patients with sepsis. Central Hypothesis: Zinc supplementation in septic subjects improves monocyte/macrophage (Mo/M¿) phagocytosis and consequently improves bacterial clearance, inflammatory balance, and mortality. Aim 1: Determine whether maximization of Mo/M¿ phagocytosis by zinc supplementation in Zn and ZD septic mice can improve bacterial burden, inflammatory balance, and mortality and determine the contribution of Fc?R and CR3 expression and function to phagocytosis Aim 2: Determine the safety and toxicity profile of zinc supplementation over a range that may impact plasma zinc status, bacterial phagocytosis, and inflammatory balance in patients with severe sepsis