BLR&D Research Career Scientist Award Application

Dr. Zhou’s research program is mainly related to the bile acid and sphingolipid-mediated signaling pathways in chronic liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), drug-induced liver disease, and cholestatic liver diseases, such as primary sclerosing cholangitis (PSC), which are major health problems both for Veterans and the general population. Understanding bile acids and sphingolipids in regulating hepatic lipid metabolism, immunity, and biliary function under different pathological conditions will provide a foundation for discovering new diagnostic markers and novel pharmaceutical interventions for the prevention and treatment of different liver diseases. Dr. Zhou’s lab has developed novel, clinically relevant animal models and techniques that allow the multidisciplinary analysis of the complex signaling pathways in the chronic disease progression, which impact the overall health of our Veterans. Dr. Zhou’s research efforts have resulted in more than 60 peer-reviewed publications, most in high- impact journals, including Hepatology, Cell Metabolism, Gut, and Nature Communication, during the last funding cycle. Dr. Zhou’s publications have been highly cited (total citations: 23073; h-index: 63). Dr. Zhou acknowledged the RCS award and VA Merit Award in her publications which were submitted from her lab after she received her RCS award in October 2018. Dr. Zhou has been actively expanding her research program by collaborating with VA physician-scientists. PTSD is a trauma- and stressor-related mental disorder which poses a significant impact on veterans’ health. The prevalence of PTSD is much higher in Veterans than in general populations, especially in combat Veterans. PTSD can result in end-organ damage, such as liver cirrhosis. Both cirrhosis and PTSD independently lead to gut dysbiosis and brain dysfunction. By collaborating with Dr. Jasmohan Bajaj, a well-known VA clinical scientist in this field, we have shown that cognitive dysfunction in Veterans with cirrhosis is linked with dysbiosis, disruption of bile acid homeostasis and alteration of short-chain fatty acids (SCFA), which result in a pro-inflammatory milieu and impairment of cognitive function in Veterans. However, alterations in the gut-liver-brain axis in Veterans with PTSD and Cirrhosis require further investigation. Dr. Zhou is a highly valued resource and member of the Central Virginia Veteran’s Health System and the affiliated university (VCU). She maintained a highly productive research program which is recognized nationally and internationally for her significant contribution to the bile acid research field. She successfully established the LC-MS/MS core for bile acid and SCFA profiling and NanoString GeoMax core via VA ShEEP grant support and has provided service to many VA-funded and academic researchers locally and nationally. Dr. Zhou will continue to expand her collaboration with other VA and non-VA scientists, especially the junior investigators new to the bile acid field. Dr. Zhou is actively involved in mentoring and training graduate students, postdoctoral fellows, physician- scientists (both early-stage and mid-career scientists), and undergraduate students. Dr. Zhou will continue to promote the research program highly relevant to Veterans’ health. Dr. Zhou continues to play an important leadership role in both local and national liver research societies. Over the past 15 years, Dr. Zhou not only maintained an outstanding research program and provided excellent mentorship for the career development of trainees and early-stage investigators but also made significant contributions to local VA, national VA, affiliated university, and professional societies during the last ten years. In summary, Dr. Zhou’s research program is nationally and internationally recognized for its focus on bile acid-mediated signaling. Her research addresses a highly significant health problem in Veterans and is particularly relevant to the overall VA healthcare mission. Dr. Zhou will continue to play an important role in facilitating collaboration and mentoring. Her effort in her role as SRCS will make significant contributions to the overall VA patient care mission.