James E. Bradner, MD
The Bradner Laboratory studies gene regulatory pathways using the emerging discipline of chemical biology. We focus on cancer, as cancer is a dreadful disease which remains largely incurable. We choose to study cancer biology with chemistry, because if we are successful in controlling cell identity in this manner, new types of chemical probes and therapeutics will emerge directly from these efforts. We consider cancer as a disease of cell state, caused by genetic alterations but influenced also by the cell type of origin and the manner in which the genome is packaged. The insight that no known set of genetic alterations is capable of causing cancer in all cell types establishes the plausibility that reprogramming the cell's fundamental identity may subvert the aggressive behavior of cancer. In addition, recent research has observed high genetic complexity, heterogeneity, plasticity and redundancy of signaling networks in cancer. These findings further establish the pressing need for molecules directed against the master regulatory proteins maintaining cancer cell identity. We have initiated research aimed at three sets of targets: (a) transcription factors, (b) chromatin-modifying enzymes and (c) histone binding modules. We invoke a utilitarian model of drug discovery which is not restricted by any individual chemistry or technology. We support a collaborative, creative approach to drug discovery focused on the most pressing targets irrespective of perceived 'druggability' or profitability.