Over 50,000 men and women will be diagnosed with head and neck cancer this year. Current treatments are generally highly toxic and there is a significant risk for metastatic recurrence which invariably leads to death. This project investigates the role of a unique intracellular pathway, the methylation of linker histones, which package DNA into the chromosomes, by the histone methyltransferase Wolf-Hirschhorn syndrome candidate 1 (WHSC1) in head and neck cancer. In cancer, it is possible that the aberrant function of linker histones contributes to cancer growth via altered chromatin structure leading to aberrant gene expression. Experiments in this project will aim to assess the effect of WHSC1-mediated methylation of linker histones on the ability of cancer cells to die, resist to chemoradiotherapy and to develop features of adaptability and thus resistance to treatment. Successful completion of this project will provide the groundwork for the introduction of novel WHSC1 inhibitors in the clinic for patients with head and neck cancer.