Robert Wood Johnson Medical School
RWJ-SPH Bldg. Room 359
683 Hoes Lane
Piscataway, NJ 08854
Genetic and microarray analysis of endogenous opioid systems; insulin-like growth factor systems in development and cancer; post-translational processing enzymes
The Pintar laboratory has used mammalian molecular genetic approaches to produce 16 lines of mice containing null alleles for genes involved in growth as well as nervous system development and function. Current work involves both the study of these mutant strains using multiple analytic levels as well as producing conditional knock-outs for several genes. Perhaps most notably, the lab has produced knock-outs of the entire opioid system and is now studying the consequences of these mutations on pain perception and anxiety as well as on drug-induced tolerance and dependence. Since specific pathways mediating these processes are interrupted in these mutants, current study involves pharmacological and biochemical approaches to determine the importance of specific second message pathways and opioid receptor dimerization on opioid receptor functions. Gene array studies are also underway to identify the molecular consequences of mutation in our mice. These studies of opioid receptor function are complemented by molecular study of how endogenous ligands for these receptors are produced, which requires the action of multiple enzymes and co-factors. Again mouse models in which these processing enzymes are mutated is a major thrust in this research. Finally, we have also produced targeted mutations of genes in the insulin-like growth factor (IGF) family. Disrupted genes alter processes as divergent as growth and cell death and may also contribute to tumorigenesis. Understanding these phenotypes, as well as the consequences of combinatorial disruption of these IGF system genes, constitutes the third current research avenue in the laboratory.