Many drugs interact with ion channels and Dr.Neil Harrison is studying how anesthetics interact with these channels. Dr. Abbott recently discovered a family of potassium channel accessory subunits and is investigating their ubiquity and necessity for generation of native potassium currents using electrophysiology and RNAi gene silencing; mutations in some of these proteins lead to cardiac arrhythmia.

Receptors are linked to intracellular events by signal transduction pathways. Many members of the Pharmacology Program work to understand these signaling cascades in the hopes of identifying novel drug targets and therapeutic strategies. Dr. Levin is investigating transductional mechanisms of a novel histamine receptor subtype (the H3-receptor), which he discovered to be activated in myocardial ischemia and afford cardioprotection. Dr. Kolesnick has discovered a new signal transduction pathway, the sphingomyelin pathway, and is identifying how this pathway signals in response to receptor activation. Dr. Levin and Dr. Buck have discovered a novel signaling pathway leading to production of the ubiquitous second messenger cAMP. The soluble adenylyl cyclase provides a local source of cAMP for intracellular compartments. This signaling pathway plays a role in cell metabolism and in sperm activation. Dr. Gross is defining signal transduction processes involving nitric oxide, a reactive gas that is produced by mammalian cells and signals by chemical modification of protein targets. Nitric oxide plays a physiological role in regulating vascular function, host defense and neuronal signaling—too much nitric oxide appears to cause clinically important vascular disease, inflammation and neurodegeneration. Dr. Hemmings is interested in the critical role played by protein phosphorylation in the effects of general anesthetics on synaptic transmission. Dr. Neal Rosen is developing new inhibitors of protein kinases to block the dysregulation of growth and inhibition of apoptosis that characterize advanced human cancer. Dr. Sauve is utilizing chemical, enzymological and pharmacological approaches to study the ADP-ribosyl-transfer enzymes CD38, Sir2 and Poly-ADP-ribosyl-polymerase (PARP). The recent discovery of important roles of these NAD+ metabolizing enzymes in cell signaling, and in regulating genome stability and lifespan make this an important research area at the present time.

Dr. Tan is developing diversity-oriented organic syntheses to identify new small molecule probes for studying biological systems. Dr. Danishefsky's lab focuses on synthesizing new drugs for cancer therapy. Dr. Okamoto is involved in the development of new muscle relaxants for use during anesthesia. Dr. Reidenberg's clinical pharmacological studies are aimed at understanding the sources of variation in drug responses. He is evaluating the mechanisms of the antineoplastic and antifertility effects of gossypol.

For more information on the Pharmacology Program of the Weill Cornell Graduate School of Medical Sciences visit: http://www.med.cornell.edu/pharmacology.