What We Do

The laboratory is an established group of researchers working on the molecular biology of growth control in normal and cancer cells.  We are focused on critical pathways that contribute to carcinogenesis (formation of cancer) and we are actively searching for new inroads to anti-cancer therapy.  Specific research areas center around cellular pathways representing high value therapeutic targets to treat the disease.   These pathways include epigenetic regulation of gene expression as well as DNA repair pathways.  We are also interested in developing new diagnostics for cancer detection in the blood stream as well as in specific organs, such as ovarian  and bladder. In addition, we are identifying drugs that inhibit or poison essential DNA binding proteins in cancer cells.  Our recent findings on epigenetic reprogramming in cancer cells are highlighted on this page to illustrate how we use modern tools of genetics, imaging, molecular biology and biochemistry to develop an understanding of a complex regulatory process in cells.  Our other projects are described in the linked pages on the navigation pane to the left, along with recent publications from my group of collaborators.

A Sample Project:  DNA Repair Induces Epigenetic Revisions in Cells.

In this project we designed mutated green fluorescent protein (GFP) genes inside cells that can be ‘switched on’ to produce GFP following a DNA breakage event.  These cells do not fluoresce green due to the mutated GFP; however, we have engineered these cells to glow green by introducing a single DNA break at a precise location in the GFP cassette.  The cells undergo what is called homologous recombination and can self correct using a breakage/rejoining pathway that all cells have to correct mutations.  When we analyzed cells that went throught this repair process, we found expression of the GFP was non-uniform.  Some cells expressed the gene (glow green) rather well, while others expressed poorly.  We have since demonstrated that these cells are different in the pattern and extent of DNA methylation, an epigenetic process that can alter gene expression (methylated cytosines at CpG repeat elements tend to shut expression down or silence the underlying gene).  The following short video illustrates nicely our findings.  Cells were induced to undergo repair of the GFP gene and we used live imaging of individual cells to show that expression of GFP is different between each daughter cell (after the cells divide).