The mission of our laboratory is to utilize knowledge learned from the immune system’s responses to cellular stress and gut bacteria to develop novel cancer therapeutics.
The Liu Lab is interested in understanding chaperone biology and unfolded protein response in B cells and plasma cells in both normal and pathological conditions. We have demonstrated that heat shock protein gp96, also known as grp94, is an essential chaperone for folding Wnt co-receptor LRP6 and that it is required for multiple myeloma cell survival, which is mediated in part by the Wnt target surviving. Additionally, we found that gp96 is highly expressed in malignant plasma cells in multiple myeloma. The higher levels of gp96 have a significant association with worse clinical stage in this disease. Our laboratory is currently studying the mechanism of gp96 in regulating myeloma initiation and progression, as well as developing gp96 target therapeutics for the treatment of myeloma.
Our laboratory is also interested in the function of dendritic cells (DCs) in cross-presenting antigens to T-cell receptors, which play essential roles in both the priming and sustenance of adaptive T-cell responses. We have generated a mouse model devoid of gp96 specifically in DCs. We discovered that the deletion of gp96 from DCs resulted in the alteration of subsets of DCs and T cells. Intriguingly, we found that targeting gp96 on DCs significantly delayed the onset of tumor development and prolonged survival in a clinically relevant, spontaneous mammary cancer model in mice. Currently, we are investigating the distinct function of DCs in the different tumor microenvironments and have developed a gp96-targeted strategy to enhance cancer immunotherapy as well as identify its clients that regulate DC functions.
The third arm of our research focuses on uncovering the mechanisms of Th17 cell differentiation in vivo. Th17 cells are important for combating fungal and bacterial infections in the oral cavity, lung and gut. Differentiation of Th17 cells takes place in the small intestine of mice colonized by SFB, Bifidobacterium adolescentis and other human commensal strains. The precise cellular and molecular events that lead to Th17 cell generation in the gut are not yet fully understood. Our laboratory has generated unique mouse models to investigate the mechanisms of Th17 differentiation now identify novel microbial metabolites that promote protective Th17 immunity in inflammation and cancers. The potential of commensal bacterial antigens as tumor vaccines is also being investigated in multiple mouse cancer models.
Affiliation: Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Contact Information
Biomedical Research Tower 588
460 W. 12th Ave.
Columbus, OH 43210
Office: 614-685-3648
Fax: 614-293-7526
Email: Bei.Liu@osumc.edu