Our laboratory is interested in the regulation of
genomic instability in mammalian cells. These studies have led us
to the investigation of cell cycle checkpoint genes which are part
of a signal transduction pathway that governs a cell1s response to
environmental cues. We use genetic, molecular, biochemical, and cytogenetic
techniques to study the cell biology of tumor cell formation and progression
in human cells.
Initial studies demonstrated that gene amplification, one type of
genomic instability, could be detected in tumor cells, but not in
normal cells. We identified the first set of genes which controls
this process in human cells. The tumor suppressor gene, p53, prevents
gene amplification in primary cells, essentially by acting as part
of a signal transduction pathway that senses genomic damage and allows
for the cell to halt cell cycle progression to increase chances for
repair. Knowledge of these control processes can be used in the diagnosis
of cancer or the identification of individuals that are predisposed
to neoplasia. We have begun screening studies to identify such individuals.
More recently, we have extended our studies to additional types of
chromosomal abnormalities, recombination, and aneuploidy. We would
like to understand how these processes are modulated in human cells
so that it can be used to increase therapeutic efficiency. Genomic
instability is known to underlie the processes of metastasis and the
generation of drug-resistant tumor cells, two events which impair
cancer treatment. Recent studies have begun to examine how altered
epithelial cell adhesion contributes to mutagenic processes. |
Biomedical Sciences (BMS) Graduate Program
