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.
Recent Publications | Additional Publications
Fugle CW, Zhang Y, Hong F, Sun S, Westwater C, Rachidi S, Yu H, Garret-Mayer E, Kirkwood K, Liu B*, Li Z. (2016) CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells. Oncoimmunology 5(10):e1226719.
Chhabra S, Jain S, Wallace C, Hong F, Liu B*. (2015) High expression of endoplasmic reticulum chaperone grp94 is a novel molecular hallmark of malignant plasma cells in multiple myeloma. J Hematol Oncol 8(1):77. [Epub ahead of print] PubMed PMID: 26108343.
Rachidi S, Sun S, Wu BX, Jones E, Drake RR, Ogretmen B, Cowart LA, Clarke CJ, Hannun YA, Chiosos G, Liu B, Li Z. (2015) Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis. J Hepatol (4):879-88.
Thaxton JE, Liu B, Zheng P, Liu Y, Li Z. (2014) Deletion of CD24 impairs development of heat shock protein gp96-driven autoimmune disease through expansion of myeloid-derived suppressor cells. J Immunol 192(12):5679-5686.
Liu B. (2014) Heat shock protein gp96 as an immune chaperone of inflammation and cancer. Austin J Clin Immunol 1(3):2.
Morales C, Rachidi S, Hong F, Sun S, Ouyang X, Wallace C, Zhang Y, Garret-Mayer E, Wu J, Liu B, Li Z. (2014) Immune chaperone gp96 drives the contributions of macrophages to inflammatory colon tumorigenesis. Cancer Res 74(2):446-59.
Kellner J, Liu B, Kang Y, Li Z. (2013) Fact or fiction--identifying the elusive multiple myeloma stem cell. J Hematol Oncol 6:91.
Hua Y, White-Gilbertson S, Kellner J, Rachidi S, Usmani SZ, Chiosis G, DePinho R, Li Z, Liu B. (2013) Molecular chaperone gp96 is a novel therapeutic target of multiple myeloma. Clin Cancer Res 19(22):6242-51.
White-Gilbertson S, Hua Y, Liu B. (2013) The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis. Front Genet 4:109. PMCID: PMC3678081
Hong F, Liu B, Chiosis G, Gewirth DT, Li Z. (2013) Alpha 7 helix region of αlpha I domain is crucial for integrin binding to ER chaperone gp96: a potential therapeutic target for cancer metastasis. J Biol Chem 288:18243-48.
Liu B, Staron M, Hong F, Wu BX, Sun S, Morales C, Crosson CE, Tomlinson S, Kim I, Wu D, Li Z. (2013) Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway. Proc Natl Acad Sci USA 110(17):6877-82.
Liu B, Staron M, Li Z. (2012) Murine but not human basophil undergoes cell-specific proteolysis of a major endoplasmic reticulum chaperone. PLoS One 7(6):e39442.
Wu S, Dole K, Hong F, Noman AS, Isaacs J, Liu B, Li Z. (2012) Chaperone gp96-independent inhibition of endotoxin response by chaperone-based peptide inhibitors. J Biol Chem 287(24):19896-903.
Wu S, Hong F, Gewirth D, Guo B, Liu B, Li Z. (2012) The molecular chaperone gp96/GRP94 interacts with toll-like receptors and integrins via its C-terminal hydrophobic domain. J Biol Chem 287(9): 6735-42.
Staron M, Wu S, Hong F, Stojanovic A, Du X, Bona R, Liu B, Li Z. (2011) Heat shock protein gp96/grp94 is an essential chaperone for platelet glycoprotein Ib-IX-V complex. Blood 117(26):7136-44.
Liu B, Yang Y, Qiu Z, Staron M, Hong F, Li Y, Wu S, Li Y, Hao B, Bona R, Han D, Li Z. (2010) Folding of toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific chaperone. Nature Communications 1(6):79.
Liu B, Nash J, Runowicz C, Swede H, Stevens R, Li Z. (2010) Ovarian cancer immunotherapy: Opportunities, progresses and challenges. J Hemato Oncol 3:7
McAleer JP, Liu B, Li Z, Ngoi S-M, Dai J, Oft M, Anthony T. (2010) Vella potent intestinal Th17 priming through peripheral lipopolysaccharide-based immunization. J Leukoc Biol 88(1):21-31.
Staron M, Yang Y, Liu B, Li J, Shen Y, Zuniga-Pflucker JC, Aguila HL, Goldschneider I, and Li Z. (2010) gp96, an endoplasmic reticulum master chaperone for integrins and toll-like receptors, selectively regulates early T and B lymphopoiesis. Blood 115(12):2380-2390.
Li Y, Zeng H, Ren-He X, Liu B, Li Z. (2009) Vaccination with human pluripotent stem cells generates a broad spectrum of immunological and clinical response against colon cancer. Stem Cells 27:3103-3111.
Liu B and Li Z. (2008) Endoplasmic reticulum HSP90b1 (grp94, gp96) optimizes B-cell function via chaperoning integrin and toll-like receptors but not immunoglobulin. Blood 112(4):1223-1230.
Wang Z, Liu B, Wang P, Dong X, Fernandez-Hernando C, Li Z, Hla T, Li Z, Claffey K, Smith JD, Wu D. (2008) Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice. J Clin Invest 118(1):195-204.
Dai J, Liu B, Ngoi SM, Sun S, Vella AT, Li Z. (2007) Toll-like receptor 4 hyperresponsiveness via cell surface expression of heat shock protein gp96 potentiates suppressive function of regulatory T cells. J Immunol 178(5):3219-3225.
Dai J, Liu B, Cua D, Li Z. (2007) Essential roles of IL-12 and dendritic cells but not IL-23 and macrophages in lupus-like diseases initiated by cell surface heat shock protein gp96. Eur J Immunol 37(3):706-715.
Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrançois L, Li Z. (2007) Heat shock protein gp96/grp94 is a master chaperone for toll-like receptors and plays critical roles in the innate function of macrophages. Immunity 26:215-226.
Liu B, Yang Y, Dai J, Medzhitov R, Freudenberg MA, Zhang PL, Li Z. (2006) TLR4 up-regulation at protein or gene level is pathogenic for lupus-like autoimmune disease. J Immunol 177(10):6880-6888.
Liu B, Dai J, Zheng H, Stoilova D, Sun S, Li Z. (2003) Cell surface expression of an endoplasmic reticulum residential heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases. Proc Natl Acad Sci USA 100:15824-9.
Liu B, DeFilippo AM, Li Z. (2002) Overcoming immune tolerance to cancer by heat shock protein vaccines. Molecular Cancer Therapeutics 1:1147-1151.
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 (Co-investigator) 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.