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Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
Email: zehner@hsc.vcu.edu
Telephone: 804-828-8753
Education
- B.A., 1969, Bradley University
- M.S., 1972, University of Houston
- Ph.D., Biochemistry, Baylor College of Medicine, Houston, TX, 1979.
Dissertation Advisor: Professor Salih J. Wakil.
Post-Doc
- Staff Fellow, Laboratory of Biochemistry, National Cancer Institute,
NIH, w/ Dr. Bruce Paterson, 1979-1980
- Muscular Dystrophy Post-doctoral Fellowship, Laboratory of Biochemistry,
National Cancer Institute, NIH, w/ Dr. Bruce Paterson, 1980-1982
Research
The overall goal of the laboratory is to understand how genes are differentially
expressed during growth, development and in cancer. Since cancer can be viewed as
de-differentiation, it is important to understand normal patterns of gene
expression and how these pathways are usurped during tumor progression.
Prostate cancer (PC) is the most common malignancy diagnosed in men and metastatic
PC represents the second highest cause of mortality. Available treatment options
for patients with hormone-refractory PC are palliative and remain mostly
ineffective with a poor prognosis of 12 months after diagnosis. Since relevant
target molecules are unknown for metastatic PC, it is necessary to find markers
that identify products involved in the transition from non-metastatic, androgen-
dependent into metastatic forms of PC. Micro RNAs (miRNAs) are non-coding, single-
stranded small RNAs that negatively regulate gene expression and constitute a new
class of gene regulators that could be relevant targets for novel therapies to
block prostate tumor progression.
To this end, the Zehner lab is identifying miRs that are differentially expressed
in models of prostate tumor progression using state-of-the art miR array screening
technologies. Tumor suppressor miRs, whose expression is low in metastatic PC cell
lines represent novel drugs, the restoration of which could combat progression of
tumor cells to the metastatic state. The effect of restoring tumor suppressor miR
expression in metastatic PC cell lines will be monitored on cell growth, signaling
pathways, apoptosis, migration, and invasion in vitro and on tumor growth in vivo.
In support of this approach we have found that restoring miR17-3p expression to a
metastatic prostate cell subline reduced tumor growth by 80% in nude mice.
Conversely, miRs that are highly expressed in metastatic PC might be acting as
oncomiRs. Their expression will be lowered by anti-miRs and the effect of this
alteration assessed in vitro and in vivo as described above. Tumor suppressor miRs
or anti-miRs represent relevant drugs to combat tumor progression whereas oncomiRs
are new targets for drug development.
The intermediate filament proteins (IFPs) provide an excellent model system for
addressing mechanisms of differential gene expression during development and in
cancer as over 30 different members have evolved to meet the specialized needs of
various cell-types. Of these, vimentin exhibits an important global expression
pattern appearing first at the delineation of the mesoderm. A number of cell-types
derive from this lineage and continue to synthesize vimentin in the fully
differentiated tissue whereas other cell-types, i.e., muscle or neural lineage,
turn-off vimentin and activate the expression of the tissue-specific IFP genes,
desmin or neurofilaments (GFAP), respectively. In addition, vimentin expression is
regulated by cell-cycle, growth factors, cytokines, tumor promoters, and viral
infection. Moreover, the vimentin gene is expressed in most, if not all, metastatic
solid tumors despite their embryological origin and is an important marker for the
epithelial-mesenchymal transition (EMT) that precedes cancer progression. An
understanding of how the same gene is down-regulated in some cells, but activated
in others remains a central question of cell biology. We are using a variety of
molecular biology and biochemical approaches to determine how the vimentin gene is
regulated during development of skeletal and heart muscle. It is clear that an
understanding of the mechanism(s) by which the vimentin gene is regulated is
important to understanding cellular controls which have gone array thereby
contributing to the metastatic tumor cell.
Publications
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1101 E Marshall St | PO Box 980614 | Richmond, VA 23298 | ph 804.828.9762 | fax 804.828.1473
Site Update July 20, 2008, Responsible Unit - Department of Biochemistry & Molecular Biology, biochemgrad@mail.vcu.edu
Virginia Commonwealth University,
VCU School of Medicine
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