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
Sepsis is the term used to describe the body's response to a serious infection and this condition is the 10th leading cause of death in the United States, killing over 215,000 patients per year. It is not well understood why people die of sepsis and the treatments for this condition are limited. Zinc has known immune regulatory properties, has been shown to decrease the duration of some infections in children, and may be beneficial in treating sepsis. This proposal is designed to answer how zinc may work in this situation and if zinc supplementation is safe in patients with sepsis.
|Exline, Matthew C; Justiniano, Steven; Hollyfield, Jennifer L et al. (2014) Microvesicular caspase-1 mediates lymphocyte apoptosis in sepsis. PLoS One 9:e90968|