Kota V. Ramana, Ph.D., Assistant Professor
Currently, our lab in association with Dr. S. K. Srivastava, Professor in the Dept. Human Biol Chem and Genetics, is involved in identifying the molecular mechanisms underlying the pathophysiology of cardiovascular complications in diabetics. We have demonstrated that the aldose reductase (AR), a member of aldo-keto reductase superfamily regulates the reactive oxygen species –mediated cytokine, chemokine, hyperglycemia, and endotoxin stimuli through the activation of NF-kappaB (Figure). Understanding the cross-talk between activation of AR and NF-kappaB is important in developing potential therapeutic approaches for secondary diabetic complications.
Specific studies in the lab include evaluation of the role of AR in bacterial endotoxin (LPS) induced signal transduction pathways leading to inflammation in mice models. Because we have shown that AR inhibition/ablation attenuates cytokine, growth factor and hyperglycemia induced activation of NF-kappaB, our hypothesis that inhibition of AR attenuates LPS-induced generation of inflammatory cytokines and chemokines, which leads to sepsis. The other interest of our research is to mechanistically understand the roles of intracellular signal transduction pathways involved in cell proliferation and death, and how interference with AR inhibition may be therapeutically exploited in the treatment of cardiovascular complications such as atherosclerosis. We have shown that inhibition/ablation of AR prevents apoptosis of vascular endothelial cells and proliferation of vascular smooth muscle cells via DAG/PLC/PKC/IKK/NF-kappaB pathway. We use a variety of cell biological, biochemical, pharmacological, and molecular genetic approaches to characterize the functional significance of AR activation/inactivation in tissue culture and animal models.
