Dr Sathish kumar Natarajan

      

Dr Sathish kumar Natarajan

Consulting Editor: Sathish Kumar Natarajan (PhD)

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

I started my research career by developing an animal model for microvesicular steatosis and showed that the administration of the peroxisome proliferator, clofibrate, results in partial protection against the oxidative damage seen in subcellular organelles and also decreases hepatic microvesicular steatosis. After this, I had established the effect of liver cirrhosis and biochemical alterations on the liver, intestine and kidney using two different experimental models to determine the mechanisms by which dysfunction in one organ system affects another organ. I have shown that liver cirrhosis results in oxidative damage to the intestinal mucosa associated with changes in the glycosylation pattern and luminal bacterial flora leading to bacterial translocation. We have also showed alterations in the levels of retinoid metabolic enzymes resulting in altered retinoid metabolites in the liver and systemic circulation during development of liver cirrhosis and later studied retinoid metabolism in the intestine using animal models of liver cirrhosis.

I had also established that proline and pipecolate metabolism promote cell survival. Proline metabolism can lead to the formation of superoxide and eventual apoptosis while biosynthesis or accumulation of proline appears to be protective against oxidative stress. These opposing properties suggest proline has a pivotal role in mediating redox homeostasis under different conditions. We have provided evidence that proline protects cells via Akt-FoxO3 signaling pathways for the cell survival during stress.

My recent work demonstrated for the first time that in addition to hepatocyte lipoapoptosis, toxic FFAs induced caspase-dependent cholangiocyte lipoapoptosis. The signaling mechanism of FFA-induced cholangiocyte lipoapoptosis is via the activation of MAP Kinases (p38 and ERK) and FoxO3 and its downstream targets like p53-upregulated modulator of apoptosis (PUMA) protein.