IRCM Researchers

The immune system provides a pivotal defence against pathogens such as viruses and malignant cells caused by mutations. It is composed of innate and adaptive immune cells, the latter contain T and B lymphocytes. The Gu lab is interested in understanding how signalling and transcriptional networks control T and B cell functions to prevent various infection, autoimmunity and cancer.

High affinity antibodies-producing B cells and memory B cells are generated in the germinal center (GC), a special structure in peripheral lymphoid organs. We are investigating molecular mechanisms that control the function of T and B cells in the GC in various animal models. Up to date, we have identified that E3 ubiquitin ligases CBLs in B cells control B cell entry into and exit from the GC, consequently determining the initiation of the GC reaction and expansion of high affinity antibody-producing B cells in GCs. In addition, we have found that CBLs in T cells are critical regulators to prevent GC reactions from producing autoantibodies responsible for lupus-like autoimmune diseases. Moreover, we have revealed recently that lysosome biogenesis play a critical role in the generation of high affinity antibody-producing memory B cells. Our current research focuses on understanding the molecular mechanisms by which CBL proteins and lysosome biogenesis exert their functions in these processes. Elucidation of these mechanisms may help to treat autoimmune diseases and design a better strategy for vaccination in the future. 

Cancer immunotherapy is a promising approach to treat various cancers. However, it is still not fully understood how the tumour microenvironment (TME) especially in solid tumours effectively suppresses anti-tumour immunity. Our lab has identified that CBL-B is an important regulator to control T cell anti-tumour immunity by regulating immune checkpoints TGF-ß, CTLA4, and PD-1 signalling. We recently also found that G protein coupled receptor (GPCR) signalling potentially may play a critical role in modulating T cell anti-tumour immunity. Our current work in this direction focuses on elucidating the mechanisms controlled by the CBL-B and GPCR signalling pathways and exploiting to target these signalling pathways for cancer immunotherapy. Our studies may provide completely new tools to prevent and treat various cancers.