Associate Professor of Biochemistry & Molecular Biology
PO Box 980614
Richmond, VA 23298-0614
Email: spdeb@hsc.vcu.edu
Telephone: 804-828-9541
Web Site: www.people.vcu.edu/~sdeb/
Education
Ph.D., Calcutta University
Research
The research interest of my laboratory is to
understand the growth regulatory mechanisms of normal
cells particularly the ones that are deregulated during
oncogenesis. At present, my laboratory is focused to
understand the mechanism of oncogenesis induced by
an oncoprotein coded by the human homologue of mouse
double minute 2 (hmdm2) gene. The hmdm2 gene product
(hMDM2) frequently overexpresses in malignant human
tumors. The oncoprotein forms complex with the tumor
suppressor p53 and inhibits p53-mediated transcriptional
activation. It also interacts with simian virus 40
T antigen in the absence of p53. The hmdm2 gene is
evolutionarily conserved among eukaryotes, which suggests
that the gene product serve an important function in
eukaryotic cells. Several hMDM2-related polypeptides
have been found in cultured mouse or human tumorigenic
cells that overexpress the protein. It is not known
which of these forms induce tumorigenesis. Amplification
of the entire mdm2 gene capable of expressing all the
spliced forms was shown to enhance tumorigenic potential
of murine cells.
Recent work from our laboratory shows that overexpression
of the full-length hMDM2 from its cDNA arrests the
G1 to S phase transition of normal human or murine
cells. Elimination of the growth inhibitory domains
of the oncoprotein induces tumorigenesis. Some cancer-derived
cell lines are partially insensitive to hMDM2-mediated
growth arrest. These observations suggest that normal
cells induce full-length hMDM2 in response to oncogenic
challenges to protect against premature cell cycle
progression. If the oncoprotein is defective in growth
arrest or if the cells are insensitive to hMDM2-mediated
growth arrest, premature progression of cell cycle
may lead to tumorigenesis. Thus hMDM2 may be a target
of viral transforming proteins such as T antigen.
At present, our goal is to understand the normal biological
function of the hMDM2 oncoprotein and how its overexpression
is involved in the etiology of cancer. We are in the
process of analyzing the growth regulatory properties
of full-length hMDM2 as well as the forms of hMDM2
overexpressed in cancer cells. We are interested to
determine the biochemical mechanism of hMDM2-mediated
growth regulation.
Publications
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