PhD, University of Illinois at Chicago
Research conducted in my laboratory focuses on understanding the early molecular events associated with viral invasion of human host cells. Our goal is to understand how viruses, exemplified by human herpes simplex viruses (HSV-1 and HSV-2) enter into susceptible cells to cause infections. Herpesviruses encode about 100 proteins from a DNA genome, which is packaged within an icosahedral capsid and a lipid-protein envelope. These human viruses cause various forms of disease, from lesions on the lips, eyes, or genitalia, to encephalitis or disseminated disease. Ocular herpes can produce a painful sore on the eyelid or surface of the eye and cause inflammation of the cornea. The less severe forms of ocular herpes include blepharitis, conjunctivitis, and epithelial keratitis. The more severe form of ocular herpes is stromal keratitis, which causes scarring of the cornea, which can lead to loss of vision and possibly blindness. The invasion of human host cells by HSV begins with an initial binding to specific cell-surface receptors.
This receptor-virus interaction then triggers fusion of viral envelope with a cell membrane. Once fused, viral capsid and some tegument proteins are released into the cytoplasm of the cell. The binding and fusion events are mediated by a number of viral envelope glycoproteins. One of the most crucial viral glycoprotein for entry is gD. It binds to three different classes of cell surface receptors, (I) a member of the tumor necrosis factor receptor (TNFR) family; (II) two members of the immunoglobulin (Ig) superfamily related to the poliovirus receptor; and special sites in heparan sulfate (HS) resulting from the action of specific 3-O-sulfotransferases. Interaction of gD with any one of these receptors triggers the membrane fusion reaction, which by an unknown mechanism also requires a concerted action of three other envelope glycoproteins namely, gB and gH-gL. Using a multifaceted approach involving genetics, molecular biology, biochemistry and cell biology we are trying to identify and characterize the viral and cellular components including intra- and inter-cellular signaling pathways that facilitate HSV entry into host cells and spread to uninfected neighboring cells. We are also interested in testing our findings in primary human cells and in vivo using a mouse model of the disease. A significant portion of our research interest is also dedicated to developing novel anti-viral agents both as tools for understating the viral invasion mechanisms and future candidates for drug development.
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