Kusum K. Kharbanda
University of Nebraska Medical Center
I have been actively involved in the field of alcoholic liver injury for more than 25 years, with special emphasis on alcohol’s deleterious effects in altering the methionine metabolic pathway and lowering the ratio of the methyl donor, S-adenosylmethionine (SAM), to its product, S-adenosylhomocysteine (SAH). In particular, I have used in vitro biochemical-based experimentation combined with in vivo animal models to define how lowering of SAM:SAH ratio and the consequent methylation defects lead to the development of many hallmark features of alcoholic liver injury such as steatosis, apoptosis, accumulation of damaged proteins, impaired proteasome function, decreased creatine synthesis and altered protein-protein interactions. We are also evaluating the efficacy of betaine and betaine analogs and esters in preventing and treating liver injury of various etiologies including alcohol and non-alcoholic steatohepatitis. Our current work has extended our studies on the alcohol/high-caloric intake-induced methylation defects on alterations in lipid droplet structure and function that leads to their persistence in the liver while promoting their lipolysis in the adipose tissue. These studies are part of funded programs to provide a comprehensive approach using biochemical, cell biological, imaging, and animal-based methods toward understanding how ethanol or western diet consumption affects the dynamics of lipid droplets in hepatocytes and adipocytes. In addition to my role as a Principal Investigator on NIH grants and VA Merit Review, I have been actively involved in mentoring young investigators.
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