# BLRD Research Career Scientist Award Application > **NIH VA IK6** · MINNEAPOLIS VA MEDICAL CENTER · 2024 · — ## Abstract Sepsis remains the leading cause of hospital mortality today. Despite its increasing incidence due to an aging population with greater comorbidities, in-hospital mortality from sepsis has significantly declined over the past decade. This decline in mortality is due in large part to earlier recognition and better compliance with best practices in early sepsis management. Despite decreased in-hospital mortality, a large fraction (up to 50% in some studies) of sepsis survivors never fully recover and develop chronic critical illness – characterized by persistent immune suppression, recurrent infections, sepsis recidivism, and poor long-term outcomes. The applicant of this BLRD Merit Review Research Career Scientist (RCS) Award is Thomas S. Griffith, Ph.D., a Research Health Science Specialist at the Minneapolis VA Health Care System (MVAHCS) currently supported by two VA Merit Awards (I01 BX001324-10 and I01 BX001324-01). Dr. Griffith is also a Professor (with tenure) in the Department of Urology at the University of Minnesota, serving as PI on two NIH grants (1R35 GM140881-01 and 1R21 AI154527-01) and co-investigator on a third NIH grant (1R01 CA260825-01). Over the past 12 years, the applicant’s laboratory has been investigating sepsis-induced immune suppression using a combination of multiple preclinical models and human samples. Current preclinical research activities in the applicant’s laboratory leverage a novel mouse model that mimics a critical aspect of human biology – exposure to multiple ongoing and resolved infections to train the immune system for robust responses to new pathogens. Environmental pathogen exposure is one important difference between basic human and laboratory mouse biology that must be considered when using mice to evaluate immune system fitness. Humans are naturally exposed to both commensal and pathogenic microbes daily from birth, and the immune system of adult humans has been trained and shaped by each infection and vaccination experienced. While specific pathogen-free (SPF) housing of laboratory mice has been instrumental in increasing experimental reproducibility, it has simultaneously further distanced the mouse as a model from humans largely because SPF mice live their lives with limited microbial exposure. Thus, the over-arching goal of the research performed in Dr. Griffith’s laboratory is to study how changing the “starting point” of the immune system (i.e., mature, adult-like immune system of ‘dirty’ mice that have experienced physiological microbial exposure vs. naïve, neonate-like immune system of SPF mice) influences the magnitude of the acute innate immune response to a septic event. Moreover, the work being done may also help to address the important fact that there is a lack of successful treatments for humans with sepsis. Over 100 agents (many targeting cytokines) with preclinical efficacy in mouse models of sepsis have been unsuccessful in humans, making it tempting to speculate the exclusive use of S... ## Key facts - **NIH application ID:** 10720892 - **Project number:** 5IK6BX006192-02 - **Recipient organization:** MINNEAPOLIS VA MEDICAL CENTER - **Principal Investigator:** Thomas S Griffith - **Activity code:** IK6 (R01, R21, SBIR, etc.) - **Funding institute:** VA - **Fiscal year:** 2024 - **Award amount:** — - **Award type:** 5 - **Project period:** 2023-01-01 → 2027-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10720892 ## Citation > US National Institutes of Health, RePORTER application 10720892, BLRD Research Career Scientist Award Application (5IK6BX006192-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10720892. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*