The long-term objective of the Chen laboratory is to identify novel mechanisms that can be targeted for developing innovative treatments for cancer and other recalcitrant human diseases. Their research focus for two decades has been on ubiquitin-like (Ubl) modifications, the regulation of which influences major oncogenic pathways and anti-tumor immunity. Even though more than 1000 enzymes/proteins are involved, Ubl modifications have been poorly addressed by FDA approved drugs, and thus are an untapped resource for new therapeutic development. The Chen laboratory has made major contributions to the discovery of new chemical and biochemical approaches to target Ubl modifications and to the elucidation of small ubiquitin-like modification (SUMO)-mediated cellular regulatory mechanisms. Her research program is transdisciplinary involving collaborations with other academic laboratories, clinicians and biotech industry.