Dr. Balabanov is currently a Clinical Associate at The University of Chicago. In the next five years, he will perform basic scientific research in transgenic models of demyelinating disorders under the mentorship of Dr. Brian Popko. His experience in neuroimmunology and transgenic technology, the enviroment at The University of Chicago and the design of his appointment make him uniquely qualified to pursue this goal. Previously, Dr. Balabanov spent five years at Wayne State University performing research in neuroimmunology. His interest in autoimmune demyelinating diseases of the CNS further matured during his neurology residency and fellowship. In his proposed research, he will study the oligodendrocyte response to interferon (IFN)-gamma and will search for the molecular mechanisms of demyelination. The University of Chicago has established neuroimmunology, myelin and transgenic laboratories. In addition, a diverse and active neurology, immunology and molecular biology faculty provides a rich training environment and numerous opportunities for collaboration. Should he receive a K08 Research Career Award, Dr. Balabanov will utilize this supportive environment to continue his education, expand his technical capabilities, and complete a university curriculum in the responsible conduct of research. Under the mentorship of Dr. Brian Popko, Dr. Balabanov will carry out a five-year research plan to define how oligodendrocytes respond to IFN-gamma. He will study the molecular aspects of their response by employing novel transgenic animal models of oligodendrocyte-restricted expression of both IFN-gamma receptor and its signaling inhibitory molecules. His research is likely to reveal not only the direct effect of IFN-gamma on oligodendrocytes but also the patterns of intracellular signaling and gene expression associated with IFN-gamma-mediated demyelination. By studying the oligodendrocyte response to IFN-gamma with this novel approach, he hopes to address problems faced by many researchers in the field.