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Calvin
James, Ph.D.
Director, Tropical Disease Institute
Associate Professor of Virology
Department of Biomedical Sciences
jamesca@ohiou.edu
Life Sciences Building 229
740-593-2355 |
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Research Interest: Viruses, because of their
limited number of genes and their total dependence
on their host for successful replication, have
proven to be excellent models for the study of
eucaryotic gene regulation. Further, it has been
documented that transcription of some of the
adenovirus early genes and a number of cellular
genes, including some oncogenes, is enhanced by
phorbol ester tumor promoters. This discovery has
been the basis for the current in vitro model for
studying phorbol ester regulation of transcription.
This model uses HeLa whole cell extracts and cloned
promoters from phorbol ester responsive and
nonresponsive genes to study transcription in an in
vitro transcription system. Recently, the focus has
been on efforts to activate the phorbol ester
receptor, protein kinase C (PKC), present in whole
cell extracts, in an effort to determine its role on
transcription of genes of interest. This system has
provided evidence that upon stimulation of PKC,
there is a parallel increase in the transcription of
adenovirus E1A gene, thus, mimicking the in vivo
observation. In contrast, there is inhibition of the
adenovirus VA gene. These observations allow a
direct biochemical test of specificity of the
induction of gene expression by phorbol esters, and
should lead to an identification of target molecules
whose phosphorylation by PKC might play a role in
gene induction. Ultimately, this work should provide
the basis for a model to define the molecular basis
for transmembrane signaling by substances which
affect gene regulation. In addition, the knowledge
gained from studies on the regulation of viral and
cellular genes could provide the basis for designing
substances that could selectively inhibit the
regulation of viral genes. |
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