Satish K. Srivastava, Ph.D.

Publications (Pubmed)

Affiliations: Department of Biochemistry & Molecular Biology
Tel: (409) 772-3926
Fax: (409) 772-9769
ssrivast@utmb.edu
Route: 0647
6.644 Basic Science Building

Satish K. Srivastava, Ph.D.

Professor

The major focus of my research is to understand the biochemical mechanism(s) of inflammatory signals that lead to a number of diseases such as diabetes, cardiovascular, asthma, COPD, cancer and metastasis. Our studies show that aldose reductase (AR) plays a pivotal role in these disorders. Reactive oxygen species, generated by various cytokines, chemokines, growth factors, environmental pollutants contribute to the activation of NF-kB and AP1, through a number of kinases which propagates the stress signals. Elevated cytokines and chemokines and growth factors cause inflammatory disorders. We have demonstrated that AR besides reducing glucose to sorbitol, efficiently reduces lipid peroxidation- derived aldehydes such as 4-hydroxynonenal (HNE) and their conjugates with glutathione. Inhibition or ablation of AR prevents the activation of redox-sensitive transcription factors such as NF-kB and AP1. Using AR inhibitors such as fidarestat, we have demonstrated that AR plays an essential role in the pathophysiology of inflammatory diseases.

We are currently investigating the molecular mechanisms that underlie the involvement of AR in diabetes, asthma, tumorigenesis and other inflammation-related diseases. These areas of research have provided additional avenues for developing therapeutic strategies for prevention or therapy of inflammation-related diseases. Indeed, we are in the process of developing AR inhibitors which could be safely used to prevent/treat the inflammatory diseases. Most importantly, AR inhibitor, fidarestat that has already undergone Phase-ii clinical trials in the USA and Phase-iii in Japan for the treatment of diabetic neuropathy and found to have no major side effects is currently being developed in my laboratory for the prevention and therapy of asthma, COPD, colon and lung cancers as well as metastasis.

Role of aldose reductase in cell signaling