The Martinez Lab uses drug discovery technology to identify novel biological regulatory pathways and potentially therapeutic small molecules.
Our current efforts are focused on the characterization of a set of compounds we have recently identified through a cell-based assay screen, which show the ability to modulate epigenetic and transcriptional events. We are analyzing the anti-cancer activity of these small molecules in human cancer cell lines and in in-vivo mouse models. The mechanism of action of these novel drugs is also being evaluated through a variety of biochemical assays and systems approaches.
Our best hit compound to date shows potent anticancer properties against non-small cell lung cancers, and breast cancer cells, while being markedly less effective in inhibiting the growth of normal cells. This small molecule triggers histone modifications, reverses telomere position silencing effects, and blocks the ability of human cancer cells to form colonies on soft agar. Our search for its molecular target(s) is underway. For this purpose, we are taking advantage of microarray technology, biochemical methods, synthetic chemistry, and comparative bioinformatics methods.
A related project aims at identifying novel ligands and novel target genes for the nuclear receptor family of transcription factors through a unique approach that correlates cancer cell responses to thousands of drugs with gene expression data through a collaboration with scientists at the NCI.
Finally, in a more clinically focused study, we are profiling epigenetic enzymes in breast cancer patient samples to identify novel molecular targets.