BLRD Research Career Scientist Award Application

AIMS: The goal of this application is to apply for Research Career Scientist (RCS) Award and to support Dr. Randy Scott Rector’s VA research program. NOMINEE: Dr. Rector is a Research Health Scientist at the Harry S Truman Memorial VA Hospital since 2011 and a tenured Professor of Medicine in the Departments of Nutrition and Exercise Physiology and Medicine at the University of Missouri School of Medicine. Dr. Rector has made significant contributions to the fields of exercise, nutrition, obesity, and steatotic liver diseases. Using technically and conceptually innovative strategies, he and his research team have been working to identify newer mechanistic targets in the hopes of developing novel therapeutics for the treatment of nonalcoholic fatty liver disease/metabolic dysfunction associated steatotic liver disease (NAFLD/MASLD), a significant problem in Veterans and civilians working for the military. Employing novel mouse models with cell-type specific knockout and overexpression of target genes and cutting-edge molecular techniques, he and his research team are investigating to mechanistically answer important questions underlying the molecular mechanisms that drive the progression of MASLD. In addition to thorough mechanistic interrogation, his lab takes integrative and translational approaches to better understand the underlying pathophysiology and altered metabolism inflicted by these conditions. In addition to MASLD, Dr. Rector’s research program at Truman VA directly focuses on various other chronic diseases that affect our Veterans, including type 2 diabetes. He has published over 170 peer-reviewed publications to date, many in the highest impact journals that include Cell Metabolism, Nature Communications, Hepatology, Diabetes, and Journal of Hepatology. His laboratory is currently funded by multiple NIH grants, a VA Merit grant, and industry-sponsored research programs. As part of his VA Research program, Dr. Rector’s lab also incorporates mentoring of trainees at all levels, from undergraduate research to training of graduate students, post-doctoral research fellows and physician scientists. IMPACT: NAFLD/MASLD has become a global epidemic, with progression to nonalcoholic steatohepatitis/metabolic dysfunction associated steatohepatitis (NASH/MASH; hepatic inflammation) and fibrosis (scarring/injury), increasing the risk for hepatocellular carcinoma, liver transplantation, and mortality. MASLD affects greater than 30% of the general US adult population, and disturbingly, prevalence rates are greater in the Veteran population. Unfortunately, there are no proven pharmacological therapies for the treatment of MASH. Studies led by Dr. Rector’s lab have provided a molecular understanding of how exercise training improves liver health in MASLD. His lab was also one of the first to establish that liver mitochondrial dysfunction is intimately linked to advanced stages of liver disease. In addition, his VA Merit funded work has shown that deletion of hepatocyte-specific endothelial nitric oxide synthase (eNOS) exacerbates hepatic steatosis and NASH, decreases hepatic mitochondrial function, increases oxidative stress, and impairs the hepatic mitophagic response. Conversely, overexpressing eNOS rescues hepatocyte mitochondrial function and attenuates MASH progression. His current VA Merit will address the critical and mechanistic role of hepatic eNOS in the regulation of hepatic de novo lipogenesis and its role in the regulation of the inflammatory and fibrogenic programming response in Kupffer cells and hepatic stellate cells in a preclinical model of MASLD/MASH. These studies will establish the cell type-specific importance of eNOS and provide further insights into reducing the incidence of MASLD/MASH in our Veteran population. In summary, Dr. Rector’s research program employs highly innovative molecular and cellular techniques and utilizes preclinical models and clinical studies to better understand human health and dis Project Number: 1IK6BX007133-01 | Fiscal Year: 2025 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: RANDY RECTOR | Institution: HARRY S. TRUMAN MEMORIAL VA HOSPITAL, COLUMBIA, MO | Activity Code: IK6 | Study Section: Special Emphasis Panel[ZRD1 RCSR-N (01)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11179631