Glenn F. Rall, PhD
Office Phone: 215-728-3617
Lab Phone: 215-728-3677
Our laboratory studies viral infections of the brain and the immune responses to those infections, with the goal of defining how viruses contribute to disease in humans, including cancer. Over the past decade, we have developed mouse models that have enabled mechanistic insights into viral replication and spread within neurons, and the roles played by soluble immune mediators, such as chemokines and cytokines, in viral clearance.
A primary objective of our work is to understand how the immune response contributes to viral clearance from the central nervous system without inducing brain damage, such as encephalitis or edema. Using a transgenic mouse model that restricts measles virus infection to CNS neurons, we have shown that both type I and type II interferons play a crucial role in clearance. Interferons, especially the type I interferons, alpha and beta, are used clinically to dampen virus infections that are associated with human cancer, such as hepatitis C. However, we do not fully understand how these immune molecules function in vivo; thus, a manipulable animal model system will be essential for understanding their mode of action, and how they may cause CNS pathology. Moreover, immunotherapy has particular appeal for resolution of brain tumors that are otherwise not approachable with existing surgical, radiological or chemical strategies. However, immunotherapeutic side effects, such as edema, pose a particular concern in the brain. Therefore, clarifying how a CNS immune response can occur without induction of immunopathology--as in our model system--is directly relevant to the development of immune-mediated approaches to resolve CNS tumors.