| Cellular
Studies of HSV.
The primary focus of my laboratory research is to carry out studies
on the cellular and molecular mechanisms that regulate the establishment
and maintenance of latent neuronal infection with herpes simplex virus
(HSV). Ongoing research is aimed at documenting the role of neuronal
gene expression in the establishment and maintenance of HSV latency.
In addition, we are studying the role of the host immune system and
the sympathetic nervous system in regulating these processes.
In related research, I have collaborated on studies aimed at understanding
regulation of the HSV LAT promoter during latent infection. The ultimate
goal of this work is to gain enough understanding of the regulation
of latent infection with herpes simplex virus that it may be possible
to devise therapeutic interventions that prevent reactivation of the
virus from the latent state.
Diagnostic PCR Assays.
A second line of investigation involves the development of polymerase
chain reaction (PCR) based assays for the diagnosis of infectious
retinitis. We have now completed assays for the detection of HSV,
varicella zoster virus and cytomegalovirus (CMV) retinitis, using
vitreous as a substrate. All three assays are rapid, make no use of
radioactive reagents, and are relatively inexpensive to run. In addition
they are highly sensitive and specific. Current work is aimed at developing
similar assays using aqueous as a substrate.
CMV Retinitis Studies.
A third line of investigation focuses on blinding CMV retinitis in
patients with AIDS - specifically, studies aimed at determining
the
molecular basis of antiviral drug resistance by CMV and the role
of strain-specific determinants of glycoprotein B in the pathogenesis
of CMV retinitis. Since the virus is extremely difficult to grow
from the eye, we use molecular techniques to amplify CMV genes of
interest
directly from the vitreous of patients with active CMV retinitis.
The amplified genes are then analyzed in order to identify DNA polymorphisms
associated with antiviral drug resistance or specific viral strains. We're
also examining the role of the medicine in the diagnosis and management
of patients with CMV retinitis. Finally, we are studying novel presentation
of CMV keratitis and iritis in otherwise healthy individuals.
VSV
Ocular Disease.
We are currently studying and describing previously unrecognized
presentations of VSV ocular disease, work aided by the use of molecular
diagnostics.
|