Department of Microbiology and Immunology
Bei Liu, MD, MPH
2000-2006 Postdoctoral Fellow, Center for Immunotherapy of Cancer and Infectious Diseases
University of Connecticut Health Center
2006-2010 Research Associate, Department of Immunology, Neag Comprehensive Cancer Center
University of Connecticut Health Center
1986 MD Tianjin Medical University, Tianjin, P.R.China
1999 MS Beijing Medical University, Beijing, P.R.China
2009 MPH University of Connecticut Health Center, Farmington, CT
Office Tel: 843-792-8994
Lab Tel: 843-792-8998
My research interests are in the areas of cancer immunotherapy, stem cell-based cancer vaccine and innate immunity. The main focus of my research is focusing on the understanding chaperone biology in B cells and plasma cells in both normal and pathological conditions. We have demonstrated that grp94 is an essential chaperone for folding Wnt co-receptor LRP6 (Liu et al., PNAS 2013) and that it is required for multiple myeloma cell survival, which is mediated in part by the Wnt target survivin (Hua et al., Clin Cancer Res 2013). More recently, we found that grp94 is highly expressed in malignant plasma cells in multiple myeloma. The higher levels of grp94 have a significant association with worse clinical stage in this disease (Chhabra et al., J Hematol Oncol 2015). Our studies have shown that grp94 is a promising therapeutic target for multiple myeloma. We will continue to study the mechanism of grp94 in regulating plasma cells and multiple myeloma as well as develop grp94 target therapeutics for treatment of multiple myeloma.
My lab is also interested in the function of dendritic cells. Dendritic cells (DCs) are professional antigen-presenting cells (APCs) which play a critical role in both innate and adaptive immune response. DCs are especially effective in cross-presenting antigens to MHC molecules and play essential roles in both the priming and sustaining of adaptive T cell response. Heat shock protein grp94 is the endoplasmic reticulum (ER) resident member of the HSP90 family. Recent genetic data demonstrate that grp94 is a master chaperone for TLRs and integrins. We have generated a novel mouse model that is specifically devoid of grp94 expression in dendritic cells but not in other cell types. By using this mouse model, the goal of this study is to understand its clients in DC homeostasis, antigen cross-presentation, as well as in tumor surveillance against both spontaneous and inflammation-induced cancer.
An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response.
Li Z, Dai J, Zheng H, Liu B, Caudill M.
Frontiers in bioscience : a journal and virtual library. 2002; 7:d731-51.
Overcoming immune tolerance to cancer by heat shock protein vaccines.
Liu B, DeFilippo AM, Li Z.
Molecular cancer therapeutics. 2002; 1(12):1147-51.
Cell surface expression of heat shock protein gp96 enhances cross-presentation of cellular antigens and the generation of tumor-specific T cell memory.
Dai J, Liu B, Caudill MM, Zheng H, Qiao Y, Podack ER, Li Z.
Cancer immunity. 2003; 3:1.
Preparation of humanized ovarian carcinoma anti-idiotypic minibody.
Chang X, Cui H, Feng J, Li Y, Liu B, Cao S, Cheng Y, Qian H.
Hybridoma and hybridomics. 2003; 22(2):109-15.
Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases.
Liu B, Dai J, Zheng H, Stoilova D, Sun S, Li Z.
Proceedings of the National Academy of Sciences of the United States of America. 2003; 100(26):15824-9.
The anti-tumor immune responses induced by a fusion protein of ovarian carcinoma anti-idiotypic antibody 6B11ScFv and murine GM-CSF in BALB/c mice.
Cui H, Chang XH, Liu B, Feng J, Li Y, Ye X, Cao SJ, Fu TY, Yao Y, Li HQ, Qian HN.
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2004; 14(2):234-41.
Combination of imatinib mesylate with autologous leukocyte-derived heat shock protein and chronic myelogenous leukemia.
Li Z, Qiao Y, Liu B, Laska EJ, Chakravarthi P, Kulko JM, Bona RD, Fang M, Hegde U, Moyo V, Tannenbaum SH, Ménoret A, Gaffney J, Glynn L, Runowicz CD, Srivastava PK.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2005; 11(12):4460-8.
TLR4 up-regulation at protein or gene level is pathogenic for lupus-like autoimmune disease.
Liu B, Yang Y, Dai J, Medzhitov R, Freudenberg MA, Zhang PL, Li Z.
Journal of immunology (Baltimore, Md. : 1950). 2006; 177(10):6880-8.
Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages.
Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrançois L, Li Z.
Immunity. 2007; 26(2):215-26. NIHMSID: NIHMS188066
TLR4 hyperresponsiveness via cell surface expression of heat shock protein gp96 potentiates suppressive function of regulatory T cells.
Dai J, Liu B, Ngoi SM, Sun S, Vella AT, Li Z.
Journal of immunology (Baltimore, Md. : 1950). 2007; 178(5):3219-25.
1R01 CA193939 Role (PI) 04/01/2016-03/31/2021
NIH/NCI “Mechanism of gp96/grp94 in regulating plasma cells and myeloma.”
The goal of this proposal is to elucidate the mechanism of gp96/grp94 in regulating plasma cell survival and multiple myeloma cell persistence during chronic ER stress and the therapeutic implications of gp96 inhibitors for myeloma.
1U01AI125859 Role (PI) 06/21/2016-05/31/2021
NIH/NIAID "Extrinsic and intrinsic factors regulating commensal-specific T helper-17 cells."
The goal of this proposal is to elucidate the mechanisms of SFB-specific Th17 cell induction.
1P01CA177575 Role (Co-leader, Project 1) 09/01/2015-08/31/2020
NIH/NCI “Endoplasmic reticulum chaperones in cancer biology and therapy.”
The goals of this program are to improve the structural knowledge of grp94 (gp96), to understand its role in cancer and immunity, and to develop grp94-targeted cancer therapeutics.
1R01DK105033 Role (Co-investigator) 12/10/2015-11/30/2020
NIH/NIDDK “Novel mechanisms of UPR sensing and nonalcoholic fatty liver disease.”
The goal of this proposal is to uncover the molecular mechanism of UPR sensing by genetic screening for novel players in the ER and to understand critically the roles of UPR in NAFLD.
R01 CA188419 Role (Co-investigator) 04/01/2015-03/31/2020
NIH/NCI "Thrombocytes in cancer immunity.”
This proposal will test the hypothesis that platelets (thrombocytes) play a role in the immune suppression of cancer by suppressing T cell anti-tumor functions and promoting myeloid-derived suppressor cells (MDSC), towards developing anti-platelet agents as adjuncts for cancer immunotherapy.