Our lab research focus is primarily on understanding the pathophysiology of nicotine addiction, the world's largest preventable cause of death.
We are studying complex neural processes at several appropriate levels: the genes, the receptor proteins, the effects on neurons, the organization of neurons in circuits, the resulting behavior of animals and testing hypotheses in a novel scientific area, "inside-out" neuropharmacology.
Biologists now believe that, like many other changes in an organism's behavior, addiction is caused by a process that links events at the surface of a cell to events at the level of the genes. This pathway is termed signal transduction pathway leading to changes in the repertoire of genes expressed by the cell which is now akin to the process of how new proteins are made leading to changes in the cell's function.
When nicotine binds to the nicotinic acetylcholine receptor it activates a cascade of intracellular pathways which can be studied in depth by easily detectable, fluorescent marker proteins. Teasing out further details of the pathway of nicotine addiction we have generated and studied mice by accentuating ( hypersensitive knock in mice) the response to nicotine rather than eliminating ( knock-out mice) it. Response to nicotine in these mice with hypersensitive subunit thus can be characterized by selective excitation such that we can quantify and localize upregulation of receptors containing that subunit.
Scientists don't understand how chronic drug use leads to addiction but the hypothesis that chaperoning, matchmaking and traffic direction are essential and sufficient is required in understanding the pathophysiology of nicotine addiction.
- Molecular and Functional Aspects of Ion Channels, Receptors, and Transporters
- Mouse Genetic Models for Neuroscience Diseases
- "Inside-Out" Mechanisms in Neuropharmacology