Free Radical Detection
Free radicals have been implicated in the pathogenesis of various diseases, or as mediators in a number of vital cellular functions. One of my major research interests is the advancement of free radical detection and identification by electron paramagnetic resonance (EPR) spectroscopy through the development of new spin traps and probes for chemical, biological and biomedical imaging applications. The spin trapping technique, using nitrone spin traps and EPR, has been widely employed for the identification of free radicals. We envision that spin traps with improved spin trapping properties will aid us in the detection and identification of free radicals in cells and animal models, and ultimately contribute towards the understanding of some of the fundamental mechanisms leading to oxidative stress or damage in biological systems.Mechanisms of Oxidative Stress
Understanding the origin of radical production in cellular systems can lead to new therapeutic strategies for the reversal and prevention of oxidative stress, and for protection against environmental-induced cardiovascular injury. Exogenously introduced chemical agents such as toxins, particulates, metal ions or ionizing radiation can induce (or may attenuate) radical production in cells. The location of radical production, whether extracellular or intracellular, remains unclear and may exhibit different pathophysiological affects. For example, extracellularly generated superoxide radical anion may affect adjacent cells and inactivate NO in the vasculature. On the other hand, intracellularly generated superoxide may cause dysfunction of the cells that produce it. Therefore, knowledge of the location of radical generation in cellular systems under pathophysiological condidtions may help develop strategies to protect cells against radical-mediated injury.
Design of Synthetic Antioxidants
The introduction of the nitrone-based, disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059), the first drug that had reached phase III clinical trials in the US in the treatment of acute ischemic stroke, has provided opportunities for the development of new and more robust pharmacological agents for the prevention of neurodegenerative diseases and ischemia-reperfusion injuries. However, the specific mechanism of nitrone bioactivity remains obscure but current findings by others indicate that this involves modulation of the intracellular redox state, suppression of gene transcription (in particular that of NF-kappa B-regulated cytokines and iNOS), and prevention of mitochondrial dysfunction. Our research focus involves interdisciplinary approach towards the development of novel synthetic antioxidants with improved pharmacological properties encompassing theoretical, synthetic, biochemical, and in-vitro/in-vivo studies.
Education and Training
PhD - Georgetown University
Post Doctoral Work: Johns Hopkins University
126A Tzagournis Medical Research Facility
420 W. 12th Avenue
Columbus, OH 43210