Currently, I am involved, in collaboration with Drs. Tim Nagy, Matthew Blaylock, and Doug Moellering, in studies aimed at elucidating the biological role of mitochondrial uncoupling protein 3 (UCP3). We hypothesize that UCP3 functions in skeletal muscle during the transition from rest to work by providing a route for the delivery of protons and electrons to mitochondrial Complex IV other than ATP synthase (Complex V) which, at rest, is inhibited by lack of its substrate ADP. UCP3, together with the G3P shuttle, serves to reoxidize NADH (generated by glycolysis in the cytosol) back to NAD, delivering its reducing equivalents to the mitochondrial electron transport chain and allowing their uncoupled oxidation under conditions of ADP deficiency. Glycolysis, which is required at the onset of muscle contraction, is thus made possible without lactate accumulation.
I am also involved in studies aimed at validating the hypothesis that homocysteine derivatizes certain proteins of the extracellular matrix, primarily fibrillin I, with resulting degradation of their biological properties. By this yet unproven mechanism, we believe that homocysteine participates in the pathogenesis of a number of diseases associated with aging. Important among them are presbyopia, vascular occlusive diseases, osteoporosis, and cognitive decline.
I continue to be interested in the role of atmospheric pollutants (e.g., tobacco smoke, ozone) in the oxidative destruction of labile vitamins, primarily tetrahydro folates, at the respiratory epithelia with the production of localized vitamin deficiencies. Support for the hypothesis that localized deficiencies of multiple vitamins occur as a consequence of exposure to oxidative pollutants and contribute to the risk of neoplastic transformation of the exposed tissues continues to accumulate. For these studies I collaborate with Dr. Chandrika Piyathilake from our department and with faculty members of the Department of Environmental Health Sciences of the School of Public Health.
I am an amateur machinist and continue working in my well-equiped home machine shop on the development of new instruments.