Research

The focus of Dr. Osawa's research is on the formation of reactive intermediates such as nitric oxide, oxygen metabolites, and drug metabolites and their subsequent interactions with important cellular targets as potential mechanisms by which drugs, environmental pollutants, and certain pathological conditions lead to toxicity or disease. Hemoproteins, such as myoglobin, hemoglobin, cytochrome P-450, nitric oxide synthase, and prostaglandin H synthase, have been of special interest to Dr. Osawa as they are important generators and targets of reactive intermediates and have critical cellular functions, including synthesis of hormones and neurotransmitters. Dr. Osawa is characterizing these interactions on the molecular level with the use of modern biological and chemical methods. He is evaluating the significance of these events in biological processes in in vitro, in vivo, and cell culture systems.

Dr. Osawa's current focus is on the regulation of neuronal nitric oxide synthase by Hsp90 and Hsp70 chaperones and the interaction of reactive intermediates on this process. Of particular interest is the finding that certain small molecule ligands of the nitric oxide synthase control the stability of the enzyme and dictate its ubiquitination and proteasomal degradation via a chaperone-mediated process. The long-term aim is to understand this fundamental process of protein quality control and to use this knowledge to control the levels of certain proteins for therapeutic benefit.

To this end, we are a member of the Chaperone Hub, a highly collaborative group in the newly formed Protein Folding Disease Initiative, that is currently testing this model of protein control for use in neurodegenerative diseases and cancer.

See Experimental Biology and Medicine 239:1405-1413 (2014) Ann Rev Pharmacol Toxicol 55:353-371 (2015) for a more detailed explanation.