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Department of Pharmacology and Therapeutics

Dr. David V. Godin Professor & Head

The research activities in the Department of Pharmacology & Therapeutics encompass the "molecule to man" description that is sometimes used to describe the wide range encompassed by our discipline. Our research endeavors fall into three major categories: Cardiovascular Pharmacology, Neuropharmacology and Clinical Pharmacology.

Our research in the Cardiovascular area focuses on the two vital components of the circulatory system, namely the myocardium and blood vessels, both of which can be the focus of common disorders of the circulatory system, and the site of action of important therapeutic agents. Molecular and cellular mechanisms involved in myocardial ischemia/reperfusion injury (such as can occur in infarction or in transplanted hearts) and in the genesis of arrhythmias are being actively investigated in three laboratories (Drs. B.A. MacLeod, D.V. Godin, M.J.A. Walker), a major focus being to devise therapeutic interventions aimed at minimizing such injury. Pathological alterations at the level of blood vessels are crucial in such diseases as hypertension and atherosclerosis. Studies of mechanisms involved in signaling by calcium and other intercellular mediators in whole blood vessels and vascular endothelial cells are being examined in the laboratories of Drs. C. van Breemen, I. Laher, X. Wang and C.C.Y. Pang. The laboratory of Dr. D.V. Godin has been involved in examining the role of reactive oxygen-derived free radicals in both ischemia/reperfusion injury and in the initiation of vascular lesions by oxidized plasma lipoproteins, leading to atherosclerotic plaque formation.

Among the areas of active investigation in the Neuropharmacology area are following: experiments examining signaling mechanisms in microglia, the immune responding cells of the brain (Dr. J.G. McLarnon); studies of synaptic communication and neuromodulation in the brain, as an approach to understanding awareness and sleep, and the actions of drugs (including anesthetics) on these states (Dr. E. Puil); plasticity of neuronal transmission and the effects of aging thereupon (Dr. B. Sastry) and studies of mechanisms of neurotransmitter release at the skeletal muscle neuromuscular junction (Dr. D.M.J. Quastel).

Investigations in Clinical Pharmacology in the Department span a rather wide range. They include studies which focus on devising new laboratory approaches to evaluating the efficacy of antiretroviral drugs (Dr. B. Conway) and anti-herpes medications (Dr. S.L. Sacks), cardiovascular drugs affecting the autonomic nervous system (Dr. R. Ragno), effects of transcranial magnetic stimulation in the management of clinical depression (Dr. A.D. Goumeniouk) and the application of “evidence-based medicine” principles in drug assessment and investigation of resulting effects on drug prescribing patterns (Dr. J.M. Wright). The Clinical Pharmacology Research Organization (CPRO) comprises a group of departmental faculty and students, at both the graduate and undergraduate levels, which focuses on the design and implementation of clinical drug trials. There is also a Division of Control Systems in the Department, an interdisciplinary research collaboration with the Department of Electrical and Computer Engineering, which is concerned with dosing-response technologies, applying advanced computer engineering techniques in combination with end-point physiological monitoring to optimizing drug delivery.

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Dr. James G. McLarnon

Dr. McLarnon's laboratory studies the biophysical properties and signaling mechanisms in human microglia, the immune responding cells of the brain. Microglia mediate inflammatory responses in the brain and are involved in the pathophysiology of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The studies are designed to better understand how microglia respond to inflammatory stimuli such as cytokines, chemokines, ß-amyloid and other agents such as ATP and to elucidate the nature of cellular functional responses such as enhanced expression and production of factors, including ones with neurotoxic potential. Imaging of calcium and other putative signaling agents is combined with patch clamp electrophysiology to study stimulus-induced cellular signaling mechanisms and RT-PCR and ELISA assays are used to examine cellular output functions. Modulatory mechanisms which are found to be neuroprotective are subsequently tested in vivo in rat brain. Pharmacological manipulation of microglial signaling pathways may prove effective in modulation of inflammatory responses in the brain in neurodegenerative diseases and stroke.