Using Molecular Structures to Fight Childhood Viruses

Viral respiratory and gastrointestinal infections are a major cause of illness and mortality in children worldwide. We are currently studying the following important childhood viruses: astrovirus, respiratory syncytial virus, parainfluenza virus, metapneumovirus, and influenza virus. Our broad research interests are to understand the molecular mechanisms of childhood viruses using a diverse toolkit of structural and biochemical techniques.  By visualizing in molecular detail how viruses enter and replicate in human cells, we can use this information to develop new vaccines and antiviral therapeutics.  

Structure-based vaccine design:  One major part of our lab is focused on how viruses enter human cells and how the immune system “neutralizes” viruses and blocks their cell entry. Using X-ray crystallography and electron microscopy, we aim to visualize the molecular structures of virus surface proteins alone, bound to human cell surface receptors, and bound to neutralizing antibodies. Analyses of these molecular structures will allow us to establish hypothesis-driven biochemical and cell-based experiments. These studies take an integrative approach to elucidate the key molecular interactions between virus and host. We will use the information derived from these studies to engineer virus surface proteins as effective vaccine immunogens that elicit virus-neutralizing antibodies. 

Structure-based drug discovery:  Another part of our lab is focused on how viruses replicate in human cells and how small molecule therapeutics can block this activity.  We are concentrating our efforts on virus RNA polymerase proteins that are required for both the replication of virus genome and transcription of virus mRNA.  Virus RNA polymerases are essential for virus survival and usually have high sequence similarity between different strains in a virus family, making these proteins ideal targets for antiviral drug development.  We are taking a multi-disciplinary approach including protein engineering, X-ray crystallography, high-throughput biochemical screening, and virology to identify high-affinity and high-specificity therapeutics that block virus replication.