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 to develop a universal stem cell-based cancer vaccine. The premise is that cancer cells share the expression of molecules (know as “oncofetal antigens”) with embryonic materials and that the immune response against these molecules in the embryonic tissues is cross-protective against cancer. We discovered that vaccination with established hES cell lines generated consistent immunological and clinical activity against a murine colon cancer. The hES cell-based vaccine is a promising modality for immunotherapy of cancer. The goal of my studies is to test if stem cell vaccine is effective against other types of cancer such as leukemia and breast cancer. We will discover the molecules that are present in both stem cells and cancer cells that can be the targets of the immune system and further dissect the detailed molecular interaction between stem cells and the host immune system.
Another research interest 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 obligate chaperone for Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6). The persistence of plasma cells as well as the development of myeloma in XBP1s-transgenic mice is critically dependent on grp94. We will continue to study the mechanism of grp94 in regulating plasma cells and multiple myeloma.
I am 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
Thaxton JE, Liu B, Zheng P, Liu Y, Li Z. Deletion of CD24 impairs development of heat shock protein gp96-driven autoimmune disease through expansion of myeloid-derived suppressor cells. J Immunol 2014, 192(12):5679-5686.
Liu B. Heat shock protein gp96 as an immune chaperone of inflammation and cancer. Austin J Clin Immunol 2014, 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. Immune chaperone gp96 drives the contributions of macrophages to inflammatory colon tumorigenesis. Cancer Res 2014, 74(2):446-59.
Kellner J, Liu B, Kang Y, Li Z. Fact or fiction--identifying the elusive multiple myeloma stem cell. J Hematol Oncol 2013, 6:91.
Hua Y, White-Gilbertson S, Kellner J, Rachidi S, Usmani SZ, Chiosis G, DePinho R, Li Z, Liu B. Molecular chaperone gp96 is a novel therapeutic target of multiple myeloma. Clin Cancer Res 2013, 19(22):6242-51
White-Gilbertson S, Hua Y, Liu B. The role of endoplasmic reticulum stress in maintaining and targeting multiple myeloma: a double-edged sword of adaptation and apoptosis. Front Genet 2013, 4:109. PMCID: PMC3678081.
Zhang Y, Helke KL, Coelho SG, Valencia JC, Hearing VJ, Sun S, Liu B, Li Z. Essential role of the molecular chaperone gp96 in regulating melanogenesis. Pigment Cell Melanoma Res 2013, 27(1):82-9. doi: 10.1111/pcmr.12165. [Epub ahead of print] PMID: 24024552.
Hong F, Liu B, Chiosis G, Gewirth DT, Li Z. 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 2013, 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. Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway. Proc Natl Acad Sci USA 2013, 110(17):6877-82.
Liu B, Staron M, Li Z. Murine but not human basophil undergoes cell-specific proteolysis of a major endoplasmic reticulum chaperone. PLoS ONE 2012, 7(6): e39442. doi:10.1371/journal.pone.0039442.
Wu S, Dole K, Hong F, Noman AS, Isaacs J, Liu B, Li Z. Chaperone gp96-independent inhibition of endotoxin response by chaperone-based peptide inhibitors. J Biol Chem 2012, 287(24):19896-903.
Wu S, Hong F, Gewirth D, Guo B, Liu B, Li Z. The molecular chaperone gp96/GRP94 interacts with toll-like receptors and integrins via its C-terminal hydrophobic domain. J Biol Chem 2012, 287(9): 6735-42.
Staron M, Wu S, Hong F, Stojanovic A, Du X, Bona R, Liu B, Li Z. Heat shock protein gp96/grp94 is an essential chaperone for platelet glycoprotein Ib-IX-V complex. Blood 2011, 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. Folding of toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific chaperone. Nature Communications 2010, 1(6):doi:10.1038/ncomms1070.
Liu B, Nash J, Runowicz C, Swede H, Stevens R, Li Z. Ovarian cancer immunotherapy: Opportunities, progresses and challenges. J Hemato Oncol 2010, 3:7
McAleer JP, Liu B, Li Z, Ngoi S-M, Dai J, Oft M, Anthony T. Vella potent intestinal Th17 priming through peripheral lipopolysaccharide-based immunization. J Leukoc Biol. 2010, 88(1):21-31.
Staron M, Yang Y, Liu B, Li J, Shen Y, Zuniga-Pflucker JC, Aguila HL, Goldschneider I, and Li Z. gp96, an endoplasmic reticulum master chaperone for integrins and toll-like receptors, selectively regulates early T and B lymphopoiesis. Blood 2010, 115(12):2380-2390.
Li Y, Zeng H, Ren-He X, Liu B, Li Z. Vaccination with human pluripotent stem cells generates a broad spectrum of immunological and clinical response against colon cancer. Stem Cells 2009, 27:3103-3111.
Liu B and Li Z. Endoplasmic reticulum HSP90b1 (grp94, gp96) optimizes B-cell function via chaperoning integrin and toll-like receptors but not immunoglobulin. Blood 2008, 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. Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice. J Clin Invest 2008, 118(1):195-204.
Dai J, Liu B, Ngoi SM, Sun S, Vella AT, Li Z. Toll-like receptor 4 hyperresponsiveness via cell surface expression of heat shock protein gp96 potentiates suppressive function of regulatory T cells. J Immunol 2007, 178(5): 3219-3225.
Dai J, Liu B, Cua D, Li Z. 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 2007, 37(3):706-715.
Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrançois L, Li Z. Heat shock protein gp96/grp94 is a master chaperone for toll-like receptors and plays critical roles in the innate function of macrophages. Immunity 2007, 26:215-226.
Liu B, Yang Y, Dai J, Medzhitov R, Freudenberg MA, Zhang PL, Li Z. TLR4 up-regulation at protein or gene level is pathogenic for lupus-like autoimmune disease. J Immunol 2006, 177(10):6880-6888.
Liu B, Dai J, Zheng H, Stoilova D, Sun S, Li Z. Cell surface expression of an endoplasmic reticulum residential heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases. Proc Natl Acad Sci USA 2003, 100:15824-9.
Liu B, DeFilippo AM, Li Z. Overcoming immune tolerance to cancer by heat shock protein vaccines. Molecular Cancer Therapeutics 2002, 1:1147-1151.
Mechanism of gp96/grp94 in regulating plasma cells and myeloma.
MUSC Bridge Funding
Determine the roles of gp96 in regulating multiple myeloma.
ACS IRG (IRG-97-219-14)
Stem cell vaccine against cancer.
South Carolina Clinical & Translational Research Institute, MUSC’s CTSA NIH/NCRR (KL2 RR029880)