Protein methyltransferases (PMTs) are involved in numerous epigenetic processes through histone and nonhistone methylation. The dysregulation of the processes has been implicated in many diseases including developmental abnormalities, neurological disorders and cancer. Among over 50 human protein lysine methyltransferases (PKMTs) and 10 human protein arginine methyltransferases (PRMTs), most of them remain to be fully characterized in regard to their substrate profiles and epigenetic functions. With our long-term goal to reveal PMT-associated epigenetic biology and target druggable PMT-associated processes for cancer therapy, the current ongoing projects in my laboratory mainly focus on the following aspects: (a) develop and apply novel technologies to profile PMT substrates and annotate their downstream functions with accurate biological or disease models (cancer, stem cells and neural diseases); (b) design and identify potent, target-specific small-molecule PMT inhibitors as structural or chemical probes, pharmacological modulators and anti-cancer reagents; (c) collaborate with structural biologists, computational biologists, caner biologists and physicians to formulate innovative concepts and approaches to identify and address emerging epigenetic questions. Our ambitious vision is to build up a highly integrated platform at the interface of chemistry and biology, and advocate it for epigenetic research and disease treatment.