Faculty

Biographical Info

Dr. Shukla studies the viral and immunological basis of ocular diseases, herpes simplex virus (HSV) pathogenesis, and the development of new anti-viral agents and vaccines. His research program is supported by the National Institute of Allergies and Infectious Diseases, Research to Prevent Blindness, Inc., and a number of other foundation grants.  Dr. Shukla has an exceptional commitment to graduate and postgraduate education and serves on important educational committees in the College of Medicine. His laboratory has trained over 25 students and pre- and postdoctoral fellows, of whom three are now independent investigators with faculty appointments.  He reviews grants for the NIH, the American Cancer Society and Midwest Eye Banks. He lends his expertise as a member of the editorial boards for two biomedical journals and serves regularly as an ad hoc and invited reviewer.  He joined the department in 2001.

Ocular Virology Laboratory

Education

PhD in Microbiology and Immunology—University of Illinois at Chicago
Postdoctoral Research Fellow in Microbiology and Immunology—Northwestern University

Research Interest

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.

Publications

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