My lab works on the regulation of gene expression
by hepatitis B virus (HBV). One project examines the mechanism of
action of the HBV posttranscriptional regulatory element (PRE), which
is an RNA element that facilitates the cytoplasmic accumulation of
viral mRNA. The PRE appears to be analogous to the Rev-response element
of HIV-1, but depends solely on host proteins for its function. We
have found two cellular proteins that bind to the PRE, and are now
assessing the role of these proteins in PRE function. We are also
characterizing the minimal cis-sequences required for PRE function,
with the goal of producing a small functional cassette that can be
used for maximizing gene expression for gene therapy and other medical
applications. Another project follows up on our discovery that one
of the HBV envelope proteins causes stress in the endoplasmic reticulum,
resulting in changes in both viral and cellular gene transcription.
We are cataloging the cellular genes activated by this protein, as
well as attempting to characterize the signaling pathway from the
endoplasmic reticulum to the nucleus. The eventual goal of these projects
is to use the information gathered to devise novel therapeutic agents
that can down-regulate HBV in the infected liver. |
Biomedical Sciences (BMS) Graduate Program
