Richard Ruan Sciences
Identifying Host Factors Critical for Dengue Virus NS1 Internalization and Pathogenesis
Dengue disease is caused by four serotypes of dengue virus (DENV), and associated symptoms can range from undifferentiated fever to severe vascular leakage. DENV nonstructural protein 1 (NS1) was recently found by the Harris laboratory and others to be a key factor in causing the endothelial barrier dysfunction that leads to vascular leakage, but the mechanism is not yet completely understood. Richard will focus on identifying possible host factors critical for NS1-induced pathology by generating a list of host factors of interest from pilot gene expression analyses, and then validating their role in endothelial dysfunction using a murine dermal leak model. Richard will then assess the therapeutic potential of small molecule inhibitors of host factors critical for NS1-mediated pathology and create modified cell lines to better understand the overall mechanism.