Yong Cang, PhDProfessor

Cancer is a leading cause of human death. Cancer arises when somatic mutations override intracellular and immunological control of cell proliferation. The ultimate goal of my laboratory research is to exploit the vulnerability of cancer and develop novel therapeutics stopping the uncontrolled growth and spreading of cancer cells. Our therapeutic development is built upon my 20 years of research expertise in the biology of the Cullin Ring Ligase 4 (CRL4) ubiquitin ligase, particularly CRL4^CRBN, and its application to targeted protein degradation. We have designed CRBN-engaging chemical libraries and screened for novel molecular glue-type degraders of cancer-driving oncoproteins, thus providing a new discovery modality to expand current oncology drug pipelines. Meanwhile, we have developed mouse models to investigate the mechanism underlying the anti-tumor immunity of lenalidomide and its analogues, which have recently been established as molecular glues to redirect CRBN for their clinical effectiveness. Our early success in this field has led us to examine genetic mutations that control cancer sensitivity to T cell-mediated cytotoxicity. Using customized CRISPR-Cas9 library screening in various tumor models, we have identified several pathways that modulate tumor growth by regulating tumor infiltrating lymphocytes, in a manner dependent or independent on the PD-1 immune checkpoint. Given the interdisciplinary and translational nature of our work, we closely collaborate with synthetic and medicinal chemists as well as computational and structural biologists.