Professor, Internal Medicine, Gastroenterology & Hepatology
Omaha VA Medical Center
4101 Woolworth Ave
Omaha, NE 68105
University of Delhi, Delhi, India, PhD, 1988
University of Delhi, Delhi, India, MS, 1981
University of Delhi, Delhi, India, BS, 1979
Areas of Interest
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.
Rasineni K, Thomes PG, Kubik JL, Harris EN, Kharbanda KK,* Casey CA.* Chronic alcohol exposure alters circulating insulin and ghrelin levels: Role of ghrelin in hepatic steatosis. Am J Physiol 316: G453-G461, 2019. * equal co-senior authors.
Listenberger L, Townsend E, Rickertsen C, Hains A, Brown E, Inwards EG, Stoeckman AK, Matis MP, Sampathkumar RS, Osna NA, Kharbanda KK. Decreasing phosphatidylcholine on the surface of the lipid droplet correlates with altered protein binding and steatosis. Cell 7, pii: E230, 2018.
Osna NA, Feng D, Ganesan M, Maillacheruvu P, Orlicky DJ, French SW, Tuma DJ, Kharbanda KK. Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury. World J Gastroenterol 22:8497-8508, 2016.
Ganesan M, Feng D, Barton RW, Thomes PG, McVicker BL, Tuma DJ, Osna NA, Kharbanda KK. Creatine supplementation does not prevent the development of alcoholic steatosis. Alcohol Clin Exp Res 40:2312-2319, 2016.