Understanding the action of drugs is a multifaceted process that begins with and builds upon the concept of molecular interactions. Many faculty members within our department focus some or all of their research on specific genes or gene products that are targets of drug action.

Dr. Margery C. Beinfeld has been studying the peptide cholecystokinin (CCK) for over 20 years. CCK is one of the most abundant peptides in the brain an appears to be an important modulator of dopamine neurotransmission as well as being closely associated with the GABAergic, glutamatergic and serotonergic systems. My laboratory currently uses molecular biologic techniques to determine which endoprotolytic enzymes are important for the processing of proCCK in endocrine and neuronal cells. Using site-directed mutagenesis and gene transfer into endocrine cells, we hope to elucidate the temporal order of cleavages of proCCK during its processing. Utilizing the same techniques, we are identifying sorting signals or domains within proCCK which direct the prohormone into regulated secretory vesicles.

Dr. John J. Castellot is exploring the regulation of gene expression by heparin, especially genes that encode proteins required for proliferation. Recent studies in his laboratory have identified several key signal transduction molecules that are inhibited by heparin, including MAPK and calcium/calmodulin activated mitogen kinase II. He have also discovered a novel growth-arrest gene that is specifically induced by heparin in smooth muscle cells. Understanding the role played by these heparin-modulated genes and signaling kinases in smooth muscle cell proliferation is a major focus of the laboratory

Dr. Alan Kopin focuses on understanding the function of cholecystokinin (CCK) and gastrin hormone receptors utilizing a variety of molecular biologic approaches. Using point mutants and chimeric receptors expressed and characterized in vitro, the lab is refining their model for how ligands bind to this family of receptors. In addition, his laboratory uses other molecular biologic techniques to identify the cascade of signaling events which link these critical amino acids to cellular proliferation and secretion. The final research area focuses on determining the physiologic role of CCK-A and CCK-B/gastrin in vivo utilizing CCK-A receptor deficient ('knockout') as well as CCK-B/gastrin receptor deficient mice which the laboratory has generated.

Dr. Richard M. Kream focuses his research on the molecular pharmacology of analgesic agents. Current analgesic agents under investigation by his laboratory include alkaloids or a combination of alkaloids and peptides.

Dr. Jeffrey A. Tatro is interested in the neuroimmune roles of receptors for melanocortins (a-MSH-related peptides), particularly in the central nervous system. Presently he and his collaborators are using molecular biologic techniques to clone the melanocortin receptors, a family of G-protein-associated proteins currently known to have five receptor subtypes.

Dr. Theoharis C. Theoharides is investigating the corticotropin-releasing hormone receptor that is expressed on mast cells as well as a 78kD protein that regulates mast cell secretion. Molecular techniques used in his laboratory include cloning, Western and Northern blotting, transfections, in situ hybridization histochemistry, cryoimmunocytochemistry as well as using antisense nucleotides to create in vitro knock-outs.

In order to understand the roles played by acetylcholine receptors in the insect nervous system Dr. Barry A. Trimmer is using molecular and physiological techniques to characterize nicotinic and muscarinic receptors in Manduca. These approaches include the isolation and cloning of muscarinic acetylcholine receptors, and acute knockout experiments using antisense oligonucleotides treatments of neurons in culture.