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Michael Imperiale

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Primary Appointment: Microbiology and Immunology
Primary PIBS Dept.: Microbiology and Immunology
Other PIBS Depts.: Cancer Biology
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 DESCRIPTION OF RESEARCH
  Our laboratory studies the molecular biology of the small DNA tumor virus, BK polyomavirus. BKPyV is a ubiquitous human pathogen that establishes a subclinical, persistent infection of the urinary tract during early childhood. In healthy individuals, the virus is excreted periodically into the urine but does not cause disease, but in renal and bone marrow transplant patients, the virus can cause severe and sometimes life threatening illnesses. We are interested in the interplay between viral and host factors that determine whether the virus will persist or replicate in the cell. On the host cell side, our current efforts are focused on nuclear factors with which the virus interacts during infection. The first of these are called promyelocytic leukemia nuclear bodies (PML-NBs), which have been reported to play various roles in the biology of the cell. In the context of BKPyV infection, PML-NBs seems to be mainly anti-viral, although some of our data indicate that they facilitate early steps in the viral life cycle. The second is the DNA damage response, which the cell normally uses to detect and repair damaged DNA. Our evidence indicates that BKPyV both induces and requires a DNA damage response for its replication. We are currently investigating why the virus interacts with the damage response machinery. On the virus side, we are uncovering the genetic determinants on the viral chromosome that regulate the switch between persistence and active replication. Since there are no effective antiviral drugs with which to treat transplant patients, we are hopeful that these studies will lead to the identification of new therapeutic targets.