Dr. Byrnes's work focuses on adenoviruses and how they behave in vivo. The cellular receptors used by the human adenoviruses that are currently in clinical trials are fairly well understood, yet the distribution of adenoviral receptors in various tissues does not directly predict how well these sites will be transduced by adenovirus vectors. After intravenous injection of adenoviral vectors, the majority of the virus is quickly phagocytosed by macrophages in the liver. This prevents the virus from reaching other organs, and can cause significant hepatotoxicity. Current studies in Dr. Byrnes's lab are aimed at understanding this phenomenon, finding out how it is related to viral receptor usage, and trying to design ways to block this rapid clearance by macrophages. In addition, because of the lack of animal models for human adenoviruses, remarkably little is known about the pathogenesis of these viruses, and we are therefore developing a model system using mouse adenovirus, a natural pathogen of mice. These studies are aimed at better understanding the behavior of adenoviruses in vivo, and allowing a better evaluation of the safety of replication-competent and replication-selective adenoviral vectors.
