Grant: Foundation Grant

Histones package our genetic information (DNA) and regulate all processes needed for a cell to grow or differentiate. There are several changes in the histone tail that act in concert with other factors (epi-genome) to govern gene activity states and the overall function of our genetic identity. Indeed, the epigenome is like the symphony of our cells, the partition that makes sense of the musical notes (DNA). Therefore, aberrant histone and chromatin modifications disrupt these normal cellular processes leading to the development of cancer. Our ground-breaking discovery of mutations in these histone genes (oncohistones as we named them with mutations at three specific residues in the histone 3 tails) in deadly brain cancers in children has linked human normal development and what we now know are epigenetic-driven cancers. We also recently uncovered oncohistones in other bone or muscle cancers, leukemia and head an neck cancers. We aim in this program to understand how this new mechanism of cancer promotes aberrant growth, identify targets amenable to therapy, provide relevant models to test the effects of these therapies prior to rapidly translating them by using our collaborative network to clinical trials at the bedside. Ultimately, if successful, our program will positively change the bleak outcome of oncohistone-associated cancers.