BLRD Research Career Scientist Award Application

Inflammatory bowel diseases (IBD) comprise chronic inflammatory pathological conditions of the gut. IBD affects ~1.6 million people in the USA where both, incidence, and disease severity are on the rise. However, situation is particularly dire for the Veterans as studies suggest that IBD is increasing at 2-3 times higher rate in Veterans

than the general population. The current IBD therapies are not curative as disease etiology remains unclear. Moreover, 25% of patients require hospitalization where 45% will have relapsing disease. Also, IBD significantly increases the risk for colon cancer. It is here noteworthy that IBD not only impacts the health and the quality of

life of affected Veterans, but it is also an expensive disease and thus a serious economic burden to patients and the VA-healthcare system. Taken together, improved understanding of IBD pathobiology and characterization of the key molecules involved in the processes critical for the IBD onset and progression, to develop novel and

promising biomarkers and therapeutic approaches, not only holds the promise of decreasing the patient mortality amongst VA-IBD patients but also reduce the associated financial burden for the Veterans Administration. The applicant’s lab program is focused on understanding the key molecular mechanism/s involving

dysregulation of specific Claudin proteins and gut microbiota in promoting the risk for IBD and its progression to Colon cancer and developing novel biomarkers and targeted therapeutics. His laboratory is internationally known for its contributions in this area, especially in understanding the role of Claudin proteins in regulating gut barrier

functions and promoting the risk for IBD in association with the gut microbiota changes. In this regard, extensive preclinical and clinical studies from his laboratory, have validated a casual role for the downregulated claudin-3 expression in promoting gut dysbiosis, IBD and its progression to colon cancer. His laboratory has further

demonstrated that claudin-3 is a tumor suppressor in colon cancer. In another project, his laboratory has become the 1st to demonstrate that PTSD (Post traumatic stress disorder), constantly increasing in Veterans population, modulates the gut microbiota and gut barrier integrity, and thus promotes intestinal inflammation. His laboratory

is performing State-of-the-Art fecal microbiota transplant (FMT) from Veterans with PTSD into the Germ-free mice to understand causal significance of the PTSD-associated gut microbiota in promoting IBD. His laboratory is also developing patient-derived organoids from known disease stages and variable therapeutic response. The

applicant has a broad background in epithelial and cancer biology, with published expertise in the regulation of IBD and colon cancer using in vivo and in vitro mouse, organoid and cell culture models. As a Research Career Scientist, he will oversee this research program by coordinating the work done; designing the experiments,

delegating, and monitoring the work to ensure that it progresses in a timely fashion. He will also be involved in preparing manuscripts of the work performed and presenting the results at conferences in this area of gastrointestinal diseases, therapeutics in IBD and colon cancer patients. Applicant’s research program has been continuously funded by VA Merit and NIH-grant awards for ~20

years. He has extensively published his research work in over 85 peer reviewed research articles in prestigious journals in the field including Gastroenterology, GUT and J Clin Invest. Yet another key hallmark of his program is a multidisciplinary and collaborative nature of the research enterprise with a deep focus on mentoring new

generation of VA and affiliated university investigators to help establish their own independent research programs. He has been successful at both the fronts: making new discoveries in the field and mentoring new generation of young scientists and establishing a solid research environment at local VA and affiliated university.

This current application is intended to highlight the success of our program and requesting RCS program to help us progress towards the new heights of success by nurturing and mentoring a new generation of investigators.