Michael G. Katze

Department of Microbiology and Washington National Primate Research Center, University of Washington, Seattle, Washington, 98195-8070 USA

Abstract:

High-throughput technologies are providing ever more comprehensive views into the intricacies of biological systems, and the ability to work with vast amounts and diverse types of data is critical to deciphering biological complexity and to advancing new therapies to combat inflammation and disease. My laboratory is using systems biology and computational approaches to understand and model integrated views of host-response networks, viral evasion of host defenses, and viral pathogenesis. In addition, we are using genomic data and novel computational methods, including geometric nonlinear analysis, to molecularly phenotype drugs and adjuvants, providing new ways to evaluate efficacy, off-target effects, and mechanisms of action. Much of our work is focused on viruses responsible for worldwide pandemics, including influenza virus, hepatitis C virus, and HIV. We are using innovative experimental systems, such as the Collaborative Cross mouse genetics platform, and are taking advantage of advances in metabolomics, lipidomics, and next-generation sequencing. These approaches are expanding our systems-level views to encompass host genetic variation, metabolic pathways, epigenetics, and the uncharted territory of noncoding RNAs, where we have observed changes in the expression of diverse classes of small and long noncoding RNAs in response to virus infection. This integrated approach is designed to provide molecular signatures that predict protective immunity or pathology, biomarkers for diagnostic or prognostic assays, and a rational basis for improvements to antiviral therapies and vaccine strategies.