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Associate Professor of Medicine; Scientist, James Graham Brown Cancer Center
Research ProgramTumor Immunobiology
Research Interests
We seek to understand the cellular and molecular mechanisms of leukocyte recruitment and priming in tumor immunotherapy by utilizing a combination of anti-tumor mAb and yeast-derived polysaccharide b-glucan. This research focuses on tumor immunotherapy mediated by anti-tumor antibodies that bind to tumors and activate complement, and which have been shown to be enhanced by co-administration of yeast-derived b-glucan. Granulocytes were discovered to be effector cells for this combination therapy. We also are attempting to determine the mechanism of action of b-glucan in hematopoietic stem and progenitor cell mobilization and radiation protection.
The second major area of interest in the lab involves the roles of B cells in the regulation of autoreactive T cell activation and tolerance using a murine systemic lupus erythematosus (SLE) model. Knowledge gained from these studies has led us to develop effective vaccines for cancer and infectious diseases.
EducationM.D., Jiangsu University School of Medicine, Medicine, 1985
M.S., Nanjing Medical University, Immunology, 1991
Ph.D., Shanghai Second Medical University, Immunology, 1997
Research and Professional Experience
1985-1988
Lecturer, Department of Microbiology & Immunology, Jiangsu University School of Medicine
1991-1994
Assistant Professor, Department of Immunology, Jiangsu University School of Medicine
1997-1999
Postdoctoral Fellow, Division of Experimental Immunology and Immunopathology, Department of Pathology, University of Louisville
1999-2001
Postdoctoral Associate, Section of Rheumatology and Immunobiology, Yale University School of Medicine
2001-2002
Associate Research Scientist, Section of Rheumatology and Immunobiology, Yale University School of Medicine
2003-2007
Assistant Professor, James Graham Brown Cancer Center, and Department of Microbiology & Immunology, University of Louisville
2007-present
Associate Professor, Department of Medicine, and Department of Microbiology & Immunology, University of Louisville
Selected Awards and Professional Honors
1996
Third prize winner of dissertation in The Advanced Course and Symposium in Immunology, organized by IUIS, Beijing, China
1998
New Investigators Award by Clinical Immunology Society
1999-present
Member, American Association of Immunologists
1998-present
Member, Clinical Immunology Society
2002
Career Development Award, S.L.E. Foundation
2003
American Association of Immunologists Junior Faculty Travel Award
2003
American College of Rheumatology Investigator Award
2003
Roger Herzig Junior Faculty Research Prize, University of Louisville
2003-present
Research Member, American College of Rheumatology
2004-present
Member, American Association for Cancer Research
PublicationsYan J, Liu GZ, Xu HX. Studies on the mechanisms involved in the dendritic cell antigen presentation. J Immunol (Chinese) 15:95-7, 1995
Yan J, Liu GZ, Xu HX. Cytokines production involved in the dendritic cell antigen presentation. J Zhenjiang Med Col 4:1-4, 1995
Yan J, Xia S, Shao QX. Preliminary studies on extraction and purification of lipid angiogeneic factor. J Chin Biopharma 16:2-4, 1996
Yan J, Ma BL, Guo XC. Role of costimulatory molecule CD80 (B7-1) in the activation of T lymphocyte. J Chin Immunol 13:79-82, 1997
Yan J, Ma BL, Wang SY. Surface marker changes on the pre- and post- CD80 (B7-1) transfected human tumor cell lines. Chin J Tumor Biother 9:20-4, 1997
Yan J, Ma BL. Studies on the relationship between costimulatory molecule CD80 (B7-1) and CD54 (ICAM-I) in the T cell activation. J Shanghai Immunol 15:21-4, 1997
Yan J, Ma BL, Guo XC. CD80 (B7-1) expression on human tumor cell lines and its costimulatory signals for T cell proliferation and cytokine production. Chin Med J 111:269-71, 1998
Yan J, Ma BL. High-efficient allo-CTL induction with costimulatory molecule CD80 (B7-1) transfected human breast carcinoma cell line in vitro. J. Shanghai Immunol 16:1-4, 1998
Yan J, Vetvicka V, Xia Y, Coxon A, Carroll MC, Mayadas TN, Ross GD. Soluble beta-glucan, a “specific” biological response modifier that targets C3-opsonized tumors in vivo for cytotoxic activation of leukocyte CR3. J Immunol 163:3045-52, 1999
Xia Y, Vetvicka V, Yan J, Hanikyrova M, Mayadas T, Ross GD. The beta-glucan-binding lectin site of mouse CR3(CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells. J Immunol 162(4):2281-90, 1999
Ross GD, Vetvicka V, Yan J, Xia Y, Vetvickova J. Therapeutic intervetion with complement and beta-glucan in cancer. Immunopharmacology 42:61-74, 1999
Yan J, Vectvika V, Mayadas TN, Ross GD. Critical role of Kupffer cell CR3 in the clearance of soluble beta-glucan or C3-opsonized erythrocytes. I mmunopharmacology 46:39-54, 2000
Doyle HA, Yan J, Liang B, Mamula MJ. Lupus autoantigens: their origins, forms, and presentation. Immunol Research 24:59-65. 2001
Yan J, Mamula MJ. B and T cell tolerance and autoimmunity in autoantibody transgenic mice. Int Immunology 14: 963-71, 2002
Yan J, Mamula MJ. Autoreactive T cell revealed in the normal repertoire: escape from negative selection and peripheral tolerance. J Immunol 168: 3188-94, 2002
Hong F, Hansen R, Yan J, Allendorf D, Baran J, Ostroff G, Ross GD. Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res 63:9023-31, 2003
Anderson B, McNiff J, Yan J, Doyle HA, Mamula MJ, Shlomchik MJ, Shlomchik WD. Memory CD4 T cells do not induce graft-versus-host disease. J Clin Invest 112:101-8, 2003
Wang T, Scully E, Yin Z, Kim H, Wang S, Yan J, Mamula MJ, Anderson JF, Craft, J, Fikrig E. IFN-gamma T cells help control murine West Nile virus infection. J Immunol 171:2524-31, 2003
Hong F, Yan J, Baran J, Allendorf D, Hansen R, Ostroff G, Xing P, Cheung N, Ross GD. Mechanism by which orally administered b(1,3) Glucans enhance the tumoricidal activity of anti-tumor monoclonal antibodies in murine tumor models. J Immunol 173:797-806, 2004
Liang FT, Yan J, Mbow ML, Sviat SL, Gilmore RD, Mamula M, Fikrig E. Borrelia burgdorferi changes its surface antigenic expression in response to immune attack. Infection Immunity 72:5759-67, 2004
Yan J, Allendorf DJ, Brandley B. Yeast whole glucan particle (WGP) beta-glucan in conjunction with antitumour monoclonal antibodies to treat cancer. Expert Opin Biol Ther 5:691-702, 2005
Yan J, Wolff MJ, Unternaehrer J, Mellman I, Mamula MJ. Targeting antigen to CD19 on B cells efficiently activates T cells. Int Immunology 17:869-77, 2005
Allendorf DJ, Yan J, Ross GD, Hansen RD, Baran JT, Subbarao K, Wang L, Haribabu B. C5a-mediated leukotriene B4-amplified neutrophil chemotaxis is essential in tumor immunotherapy facilitated by anti-tumor monoclonal antibody and beta-glucan. J Immunol 174:7050-6, 2005 (Corresponding author)
Yan J, Harvey BP, Gee RJ, Shlomchik MJ, Mamula MJ. B Cells drive early T cell autoimmunity in vivo prior to dendritic cells-mediated autoantigen presentation. J Immunol 177:4481-7, 2006
Cramer DE, Allendorf DJ, Baran JT, Hansen R, Marroquin J, Li B, Ratajczak J, Ratajczak MZ, Yan J. Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury. Blood 107:835-40, 2006
Ding C*, Wang L*, Al-Ghawi H, Marroquin J, Mamula M, Yan J. Toll-like receptor engagement stimulates anti-snRNP autoreactive B cells for activation. (*co-first author). Eur J Immunol 36:2013-24, 2006 (Editor’s commentary)
Li B, Allendorf D, Hansen R, Marroquin J, Ding C, Cramer D, Yan J. Yeast beta-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via CR3-Syk-PI3-kinase pathway. J Immunol 177:1661-9, 2006
Ratajczak MZ, Reca R, Wysoczynski M, Yan J, Ratajczak J. Modulation of the SDF-1-CXCR4 axis by the third complement component (C3) – Implications for trafficking of CXCR4+ stem cells. Exp Hematol 34:986-95, 2006
Reca R, Wysoczynski M, Yan J, Lambris JD, Ratajczak MZ. The role of third complement component (C3) in homing of hematopoietic stem/progenitor cells into bone marrow. Adv Exp Med Biol 586:35-51, 2006
Xu H, Chilton P, Tanner M, Huang Y, Schanie C, Dy-Liacco M, Yan J, Ildstad ST. Humoral immunity is the dominant barrier for alogeneic bone marrow engraftment in sensitized recipients. Blood 108(10):3611-9, 2006
Ding C, Yan J. Regulation of autoreactive B cells: checkpoints and activation. Arch Immunol Ther Exp (Warsz) 55(2):83-9, 2007
Li B*, Allendorf D*, Hansen R, Marroquin J, Cramer DE, Harris CL, Yan J. Combined yeast beta-glucan and anti-tumor mAb therapy require C5a-mediated neutrophil chemotaxis via regulation of decay accelerating factor CD55. (*two authors contributed equally) Cancer Res 67:7421-30, 2007
Li B, Cramer D, Wagner S, Hansen R, King C, Kakar S, Ding C, Yan J. Yeast glucan particles activate murine resident macrophages to secrete proinflammatory cytokines via MyD88- and Syk kinase-dependent pathways. Clin Immunol 124(2):170-81, 2007 (Cover art)
Xu H, *Yan J, *Huang YM, Chilton PM, Ding CL, Schanie CL, Wang L, Ildstad ST. Co-stimulatory blockade of CD154:CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization. Blood, Sep 7; [Epub ahead of print] PMID: 17827394 (*two authors contributed equally)
Xu H, Yan J, Ildstad ST. Xenotransplantation: a step closer to reality? Blood 110:3815, 2007 (Commentary)
Reca R, Cramer D, Yan J, Laughlin M, Janowska-Wieczorek A, Ratajczak J, Ratajczak M. A novel role of complement in mobilization; immunodeficient mice are poor mobilizers because they lack complement-activating immunoglobulin. Stem Cells 25(12):3093-100, 2007
Xu H, Chilton PM, Huang Y, Schanie CL, Yan J, Ildstad ST. Addition of cyclophosphamide to T-cell depletion-based nonmyeloablative conditioning allows donor T-cell engraftment and clonal deletion of alloreactive host T-cells after bone marrow transplantation. Transplantation 15:83(7):954-63, 2007
Salvador C, Li B, Hansen R, Cramer D, Kong M, Yan J. Yeast-derived beta-glucan augments the therapeutic efficacy mediated by anti-vascular endothelial growth factor monoclonal antibody in human carcinoma xenograft models. Clin Cancer Res 14(4):1239-47, 2008
Contact InfoCTR Building
505 South Hancock Street
Louisville, KY 40202
Phone: (502) 852-3628
Fax: (502) 852-2123
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