仓勇

实验室研究蛋白泛素化降解调控及其在发育和疾病生成中的作用, 同时也探索小分子化合物劫持泛素连接酶用于治疗癌症和调节免疫功能的机制。具体有两个方向的研究：

1. 靶向蛋白降解的新型分子胶水化合物的发现，机制研究，及其在癌症治疗领域的应用。

2. 用遗传和化学手段研究T细胞控制癌症细胞生长和转移的机制。

实验室常用实验手段包括：

1. 癌症细胞生物学技术

2. 基因敲除/敲入小鼠模型

3. CRISPR基因组体外和体内筛选

4. 化学生物学技术

5. 生物信息分析

Introduction to Cang Lab:

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.