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Office: 803 434 3581
Fax:
E-mail:
creek
@uscmed.sc.edu
Department of Pathology and Microbiology, University
of South Carolina School of Medicine, Columbia, SC 29208
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My
research program centers on exploring the cellular and molecular changes
initiated by human papillomavirus type 16 (HPV16), a DNA virus associated
with nearly all cervical cancers. In particular we use an in vitro model
system of HPV-mediated human cell carcinogenesis. Using this model we have
characterized several key changes that mark the progression from normal to
premalignant cells upon transfection of normal human keratinocytes (HKc)
with HPV16 DNA. We have determined that progression in this model is
associated with increasing resistance to growth inhibition by transforming
growth factor-beta (TGF-beta). TGF-beta resistance is the result of a loss
in the expression of the TGF-beta receptor type I (TGF-beta RI). Current
studies, funded by the National Cancer Institute (NCI), are exploring the
molecular mechanism(s) leading to a loss of TGF-beta RI in these cells.
Additional areas of focus in my laboratory include; (1)
studies exploring the specific functions of the HPV16 E6 and E7 oncoproteins
required to induce TGF-beta resistance and disrupt TGF-beta signaling in
normal HKc and (2) experiments aimed at identifying the elements within the
HPV16 upstream regulatory region (URR) that are responsible for TGF-beta
modulation of HPV16 early gene expression. Our recent results, published in
the Journal of Virology, demonstrate that TGF-beta modulation of HPV16 early
gene expression is mediated by NF1/Ski interactions.
A long term goal of our research is to determine which
markers of progression identified in our in vitro model can be verified and
tested in the human population. To this end we are employing a DNA
microarray approach, using both our in vitro model system and cervical cells
collected from routine Pap smears. These studies are being conducted in our
microarray core facility, which I serve as Director. We hope to identify
biological markers of cervical cancer progression that will find an
application in screening, using “diagnostic” DNA microarrays, to ultimately
identify among HPV positive women, those at greatest risk to develop
cervical cancer.
Finally, in a program recently funded by the NCI, I am
coordinating a project that brings together Claflin University (a
Historically Black College or University located in Orangeburg, South
Carolina) and the South Carolina Cancer Center in a collaborative effort
aimed at training minority undergraduate students in cancer research, and at
establishing solid collaborative research programs among cancer researchers
at the two institutions. |
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