Our laboratory is focused on studying the pathogenesis of the human polyomaviruses, JC Virus (JCPyV) and BK Virus (BKPyV). Reactivation of JCPyV under conditions of immunosuppression leads to the fatal demyelinating disease in humans known as Progressive Multifocal Leukoencephalopathy (PML). Reactivation of BKPyV in kidney transplant recipients has emerged as a major problem in the last decade and is responsible for nearly half of all kidney transplant failures.
The major focus of the lab is studying early events that mediate infection of cells by these viruses. These early events include but are not limited to studies of virus-host cell receptor interactions, endocytic trafficking of virus from the plasma membrane to the nucleus, and virus induced membrane signaling.
We have a general interest in studying events that contribute to viral tropism and regulate the balance between infection and resistance. We also focus our efforts at screening lead compounds that block any of these key steps in the viral life cycle as potential therapies to treat or prevent disease caused by JCV and BKV. We approach these problems using state-of-the-art techniques in cell and molecular biology and genetics.
Virus-Host Cell receptor Interactions
- Identify host cell receptors and co-receptors for the human polyomaviruses, JCV and BKV
- Determine the cell and tissue distribution of virus receptors
- Identify factors that increase or decrease virus receptor expression on cells and in tissues
- Identify critical residues in the viral capsid that mediates binding to virus receptors
- Define the role of the cytoskeleton in trafficking of virus from the plasma membrane to the nucleus
- Determine the mechanism by which JCV and BKV deliver their respective genomes across the nuclear membrane
- Identify the site and mechanism of virus uncoating
- Characterize molecular signals induced upon virus binding to host cell surfaces
- Characterize downstream signal transduction events and define how they impact viral infection
- Define the cellular and viral determinants that mediate signaling
Genetics and Genomics
- Identify host cell genes that are turned on or off in response to viral infection
- Identify genes that are differentially expressed in cells that are resistant to JCV infectionf versus cells that are susceptible to infection
- Identify compounds capable of preventing the establishment of viral infection in host cells and interfering with the replication and growth of human polyomaviruses
- Identify risk factors for the development of PML in HIV infected and other immunosuppressed patient populations
- Identify risk factors for the development of BKV associated nephropathy in kidney transplant recipients