Candidate: The candidate, Matthew Exline, M.D. is an Assistant Professor in the Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine at the Ohio State University. Dr Exline has a history of investigating the innate immune response during sepsis with emphasis on immune suppression due to apoptosis of immune cells or mechanisms of monocyte deactivation. In addition, he has a specific interest in biomarkers of sepsis. His short-term goal is to augment the basic science training he has already received with training in clinical research including study design and statistical analysis. His long-term goal is to become a successful independently funded translational researcher in critical care and sepsis. Career Development: Dr Exline's career development will include formal training in a Master of Public Health in Clinical Investigation program that will be mentored by Dr. Philip Binkley. The curriculum will include his mentored research project and formal didactics in study design, biostatistics, grant writing, and bioethics. In addition, Dr. Exline will continue to work in the laboratory on several ongoing projects directed at understanding the mechanistic pathways involved in inflammatory cell responses to pathogen challenge. Environment: Dr Exline is currently in an environment that is conducive to his development as a translational researcher. There is a large ICU patient population and support in the form of clinical coordinators and laboratory technicians. Dr. Exline's mentors, Drs. Wewers and Binkley have an outstanding history as mentors and as scientists with an established track record of extramural funding. Research: Dr. Exline's general goal is to investigate mechanisms of immune suppression during sepsis. His specific aims are: 1) determine if immune suppression during the recovery from critical illness is greater in severe sepsis patients compared to non-septic patients and 2) prospectively evaluate if there is an association between severe sepsis and nosocomial infections mediated by immune paralysis. To accomplish this Dr. Exline will measure changes in innate immune system proteins termed the inflammasome and correlate these to the patient's admission diagnosis, septic or non-septic, and outcome including the risk of nosocomial infections. In addition, the candidate will follow a large cohort of approximately 460 patients, determine their baseline immune function, and evaluate whether sepsis is an independent risk factor for nosocomial infections. RELEVANCE (See instructions): Sepsis is the body's response to a severe infection. Unfortunately, despite aggressive treatment with antibiotics and life-support, approximately a third of patients with severe sepsis will die. Many of these patients die not from the original infection, but from a second infection they acquire in the hospital. We propose to study how sepsis weakens the body's immune system and makes these patients at risk for these secondary infections and death. Our findings may lead to new treatments for this devastating disease. (End of Abstract)