Department Directory

Zendra E. Zehner, Ph.D.

Zendra E. ZehnerProfessor of Biochemistry & Molecular Biology

PO Box 980614
Richmond, VA 23298-0614

Telephone: 804-828-8753

  • 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.
  • 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

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.


View Dr. Zehner's Publications via the National Library of Medicine's PubMed.


VCU Department of Biochemistry and Molecular Biology Virginia Commonwealth University VCU Medical Center
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