Toshinori Hoshi, Ph.D.

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				Toshinori Hoshi, Ph.D. Professor Department of Physiology School of Medicine D 100 Richards Building email: hoshi@hoshi.org Click here for selected publications since Dr. Hoshi's arrival at Penn RESEARCH INTERESTS Oxidative regulation of neuronal excitability; ion channel gating; protein oxidative damage and aging. RESEARCH TECHNIQUES Electrophysiology (patch clamp, voltage-clamp, extracellular recording, optical recording); molecular biology; tissue culture; Drosophila genetics, physiology and behavior. RESEARCH SUMMARY My laboratory investigates roles of amino-acid oxidation in physiology. Reactive molecules capable of inflicting oxidative damage to proteins critical in cell function are inevitably generated during the course of normal metabolism. We postulate that oxidative modification of proteins is an important regulator of many physiological processes, including neuronal excitability. We experimentally manipulate the redox state of single proteins, single cells, tissues or animals by pharmacological and genetic means and examine how these interventions change their functional properties. For example, we study how genetic manipulations of anti-oxidant enzymes alter functional properties of ion channels using biophysical and electrophysiological methods. In addition, we are investigating how oxidation of the amino acid methionine contributes to biology of normal aging using the fruit fly Drosophila as a model system. We manipulate cellular redox states genetically and examine the lifespan and senescence-associated changes in physiology and behavior. We anticipate that this investigation will be extended to other organisms. KEY WORDS: neuronal excitability, ion channel gating, oxidation, methionine, aging