Mechanistic Studies on Retroviral Gene Transfer to Epithelial Cells

Andreadis BES-0354626 The objective of this study is to identify the mechanism through which integrins mediate retroviral gene transfer. Two different but not mutually exclusive hypotheses will be tested. First, it will be examined if integrins are involved in binding to the cell surface and/or internalization of retroviral particles in the cell cytoplasm. Second, it will be examined which - if any - integrin-mediated signaling pathway(s) affect the retroviral life-cycle and consequently gene transfer. The intellectual merit of the proposed studies lies in their potential to increase the understanding of virus-cell interactions and provide novel ways to promote gene transfer to the stem cell compartment of the skin. Such advances will improve the capacity of epidermal keratinocytes for treatment of disease or injury and the prospect of tissue engineered skin as isbioreactorla for local or systemic delivery of therapeutic proteins. The proposed studies are designed to have significant broader impact by integrating research and education, by engaging participation of underrepresented minorities and by broad dissemination of research results using state-of-the-art communication technologies.