BLRD Research Career Scientist Award Application

Project Summary Inflammatory bowel disease (IBD) is a family of chronic disorders of the intestine afflicting nearly 3 million Americans. Consisting of Crohn’s disease (CD) and ulcerative colitis (UC), IBD is significantly increasing in severity and prevalence worldwide and represents a disease with one of the highest hospitalization rates among American veterans. Incidence of IBD among military service members is estimated to be 2-10 times greater than non-service members, with a striking relationship between IBD incidence and the number of life stressors. It is notable that the pathogenesis of IBD is incompletely understood. Ongoing work by us and labs around the world suggests that imbalances in the gut microbiome (termed dysbiosis) in combination with abnormal mucosal innate immunity play central roles in in the pathogenesis of IBD. It is also clear that ongoing inflammatory responses are associated with profound shifts in tissue metabolism that fundamentally influence barrier function and wound healing. These studies have strongly implicated a loss of energy balance (i.e., “starved gut”) as a driving force in the pathogenesis of IBD. Our ongoing studies are utilizing multi-disciplinary approaches to identify molecular targets to bolster energy metabolism and promote inflammatory resolution in mucosal inflammation. We hope to translate this fundamental research into the development of novel therapeutics for veterans. The research described in this Research Career Scientist Award proposal is highly collaborative in nature, involving scientific interactions with multiple investigators at the Rocky Mountain Regional Veterans Affairs Medical Center as well as investigators at the San Diego Regional VA Medical Center. I plan to continue fostering and expanding these productive collaborations. The Rocky Mountain Regional VA Medical Center and the Denver metro area provides a fertile training ground for biomedical research Training of junior faculty, graduate students and postdoctoral fellows are essential components of this Research Career Scientist Award. We will continue building the infrastructure and mentoring environment to attract CDA2 candidates, and thus help train the next generation of outstanding VA scientists.