Department of Microbiology and Immunology
Xue-Zhong Yu, MD
Department of Microbiology & Immunology
Department of Medicine
Distinguished Endowed Chair
SmartState Cancer Stem Cell Biology & Therapy Program
Medical University of South Carolina
Dr. Yu received a Bachelor of Science degree in Medicine (an MD equivalent) and then a Master of Science in Immunology from Peking University Health Sciences Center in Beijing China. After his residency in Nanchang China, he completed a postdoctoral fellowship at the Fred Hutchinson Cancer Research Center in Seattle, Washington.
Phone: (843) 792-4756
Office: HCC HO350
Lab: HCC HO356
The research in Dr. Yu’s Lab focuses on the biology of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) after allogeneic hematopoietic stem cell transplantation (HSCT). The ultimate goal of these studies is to prevent or treat GVHD while preserving GVL effect, which could greatly enhance the therapeutic potential of HSCT. Because T cells play central role to induce GVHD and mediated GVL effect, understanding T-cell response to normal tissue versus tumor cells is critical for achieving the ultimate goal. The major lines of current work in Dr. Yu’s Lab include: 1) T-cell differentiation and GVHD development; 2) Biology of regulatory T cells and their potential application in the control of GVHD; 3) Control of GVHD development by targeting protein kinases essential for T-cell survival and function; 4) Evaluation of metabolic pathways or intermediates as biomarkers and therapeutic targets in GVHD and leukemia relapse.
Yu XZ and Anasetti C. Enhancement of susceptibility to Fas-mediated apoptosis of Th1 cells by nonmitogenic anti-CD3ε F(ab;)2. Transplantation 69(1):104,2000.
Yu XZ, Bidwell SJ, Martin PJ, and Anasetti C. CD28-specific antibody prevents graft versus-host disease in mice. J Immunol 164(10):4564, 2000.
Yu XZ, Bidwell SJ, Martin PJ, and Anasetti C. Anti-CD3 F(ab’)2 prevents graft-versus-host disease by Electively depleting donor T cells activated by recipient alloantigen. J Immunol 166(9):5838, 2001.
Yu XZ, Martin PJ, and Anasetti C. CD28-signal enhances apoptosis on CD8 T cells upon strong TCR ligation. J Immunol 170(7):3002, 2003.
Yu XZ, Levin SD, Madrenas J, and Anasetti C. Lck required for activation-induce death after TCR ligation with partial agonists. J Immunol 172(3):1437, 2004.
Yu XZ, Albert, MH, and Martin PJ, and Anasetti C. CD28 ligation induces transplantation tolerance IFNγ-dependent depletion of T cells that recognize alloantigen. J Clin Invest 113(11):1624, 2004.
Albert MH, Yu XZ, Martin PJ, and Anasetti C. Prevention of lethal acute GVHD with an agonistic CD28 antibody and rapamycin. Blood 105(3):1355, 2005.
Albert MH, Martin PJ, Anasetti C, and Yu XZ. Antigen-dependent suppression of alloresponses by Foxp3-induced regulatory T cells in transplantation. Eur J Immunol 35:2598, 2005.
Yu XZ, Liang Y, Nurieva RI, Guo F, Anasetti C, and Dong C. Opposing effects of ICOS on graft-versus-host disease mediated by CD4 and CD8 T cells. J Immunol 2006 176(12):7394-401, 2006. PMID: 16751384
Yu XZ, Albert MH, and Anasetti C. Alloantigen affinity and CD4 help determine severity of graft-versus-host disease mediated by CD8 donor T cells. J Immunol 176(6):3383-90, 2006. PMID: 16517706
Nurieva, RI, Thomas s. Nguyen T, Martin-Orozco N, Wang Y, Kaja MK, Yu XZ, and Dong C. T-cell tolerance of function is determined by combinational co stimulator signals. EMBO J 25(11):2623, 2006.
Liang Y, Liu C, Djeu JY, Zhong B, Peters T, Scharffetter-Kochanek K, Anasetti C, and Yu XZ. Beta2 integrins separate graft-versus-host disease and graft-versus-leukemia effects. Blood 111(2):954-62, 2008. PMID: 17928532
Wang H., Peters T, Sindrilaru A, Kess D, Oreshkova T, Yu XZ, Seier AM, Schreiber H, Wlaschek M, Blakytny R, Rohrbein J, Schulz G, Weiss J, and Scharffetter-Kochanek K. TGF-beta-dependent suppressive function of Tregs requires wild-type levles of CD18 in a mouse model of psoriasis. J Clin Invest 118(7):2629-39, 2008.
Guo F, Iclozan C, Suh WK, Anasetti C, and Yu XZ. CD28 controls differentiation of regulatory T cells from naive CD4 T cells. J Immunol 181(4):2285-91, 2008. PMID: 18684917
Yu Y, Iclozan C, Yamazaki T, Yang X, Anasetti C, Dong C, and Yu XZ. Abundant c-Fas-associated death domain-like interleukin-1-converting enzyme inhibitory protein expression determines resistance of T helper 17 cells to activation-induced cell death. Blood 114(5):1026-8, 2009. PMID: 19429865
Valenzuela JO, Iclozan C, Hossain MS, Prlic M, Hopewell E, Bronk CC, Wang J, Celis E, Engelman RW, Blazar BR, Bevan MJ, Waller EK, Yu XZ, and Beg AA. PKCtheta is required for alloreactivity and GVHD but not for immune responses toward leukemia and infection in mice. J Clin Invest 119(12):3774-86, 2009. PMID: 19907075
Iclozan C, Yu Y, Liu C, Liang Y, Yi T, Anasetti C, and Yu XZ. T helper17 cells are sufficient but not necessary to induce acute graft-versus-host disease. Biol Blood Marrow Transplant 16(2):170-8, 2010. PMID: 19804837
Semple K, Yu Y, Wang D, and Yu XZ. Efficient and selective prevention of graft-versus-host disease by antigen-specific induced regulatory T cells in mice. Biol Bone Marrow Transplant 17(3):309, 2011.
Semple K, Nguyen A, Yu Y, Anasetti C, and Yu XZ. Strong CD28 costimulation suppresses generation of induced regulatory T cells from naïve precursors through Lck signaling. Blood 117(11):3096, 2011.
Li J, Semple K, Liu C, Chen F, Blazar BR, and Yu XZ. Role of CD28, CTLA4 and ICOS in acute graft versus-host disease mediated by CD4 T cells in mice. Biol Bone Marrow Transplant 17(7):962, 2011.
Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, and Yu XZ. Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood 118(18):5011-20, 2011. PMID: 21856864
Veerapathran A, Pidala J, Beato F, Yu XZ, and Anasetti C. Ex vivo expansion of human Tregs specific for alloantigens presented directly or indirectly. Blood 118(20):5671-80, 2011. PMID: 21948174
Yu Y, Yu J, Liu C, Iclozan C, Kaosaard K, Anasetti C,and Yu XZ. Bim is required for T-cell allogeneic responses and graft-versus-host disease in vivo. Am J Blood Res 2(1):77, 2012.
Wang D, Iclozan C, Liu C, Xia C, Anasetti C, and Yu XZ. LBH589 enhances T cell activation in vivo and accelerates graft-versus-host disease in mice. Biol Blood Marrow Transplant (8):1182-1190, 2012. PMID: 22698484
Yu Y, Cho HI, Wang D, Kaosaard K, Anasetti C, Celis E, and Yu XZ. Adoptive transfer of Tc1 or Tc17 cells elicits antitumor immunity against established melanoma through distinct mechanisms. J Immunol 2013 Feb 15;190(4):1873-81. PMID: 23315072
Wang D, Yu Y, Haarberg K, Fu J, Kaosaard K, Nagaraj S, Anasetti C, Gabrilovich D, and Yu XZ. Dynamic change and impact of myeloid-derived suppressor cells in allogeneic bone marrow transplantation in mice. Biol Blood Marrow Transplant (5):692-702, 2013. PMID: 23376089
Li J, Heinrichs J, Leconte J, Haarberg K, Semple K, Liu C, Gigoux M, Kornete M, Piccirillo CA, Suh WK, and Yu XZ. Phosphatidylinositol 3-Kinase-Independent Signaling Pathways Contribute to ICOS-Mediated T Cell Costimulation in Acute Graft-Versus-Host Disease in Mice. J Immunol 191(1)200- 2013. PMID: 23729441
Yu Y, Wang D, Kaosaard K, Liu C, Fu J, Haarberg K, Anasetti C, Beg AA, and Yu XZ. C-Rel is an essential transcription factor for the development of acute graft-versus-host disease in mice. Eur J Immunol 43(9):2327, 2013. PMID: 23716202
Veerapathran A, Pidala J, Beato F, Betts B, Kim J, Turner JG, Hellerstein MK, Yu XZ, Janssen W, and Anasetti C. Human regulatory T cells against minor histocompatibility antigens: ex vivo expansion for prevention of graft-versus-host disease. Blood 122(13):2251, 2013.
Haarberg MK, Li J, Jeinrichs J, Wang D, Liu C, Bronk CC, Kaosaard K, Owyang AM, Holland S, Masuda E, Tso K, Blazar BR, Anasetti C, Beg AA, and Yu XZ. Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice. Blood 122(14):2500, 2013. Featured Article in that Issue.
Betts BC, Veerapatharan A, Pidala J, Yu XZ, and Anasetti C. STAT5 polarization promotes iTregs and suppresses human T-cell alloresponses while preserving CTL capacity. J Leukoc Biol 95(2):205, 2014.
Chatterjee S, Thyagarajan K, Kesarwani P, Song JH, Soloshchenko M, Fu J, Bailey SR, Vasu C, Kraft AS, Paulos CM, and Yu XZ and Mehrotra S. Reducing CD73 expression by IL1β-programmed Th17 cells improves immunotherapeutic control of tumors. Cancer Res 74(21):6048, 2014.
Bronk CC, Yoder S, Hopewell EL, Yang S, Celis E, Yu XZ, and Beg AA. NF-κB is crucial in proximal T-cell signaling for calcium influx and NFAT activation. Eur J Immunol 44(12):3741, 2014.
Fu J, Wang, Yu Y, Heinrichs J, Wu Y, Schutt S, Kaosaard K, Liu C, Haarberg K, Bastian D, McDonald DG, Anasetti C, and Yu XZ. T-bet is critical for the development of acute graft-versus-host disease through controlling T-cell differentiation and function. J Immunol 194(1):388, 2015.
Xiao G, Wang X, Sheng J, Lu S, Yu XZ, and Wu JD. Soluble NKG2D ligand promotes MDSC expansion and skews macrophage to the alternatively activated phenotype. J Hematology & Oncology. 8:13, 2015.
Wu Y, D Bastian, S Schutt, HD Nguyen, J Fu, J Heinrichs, C Xia, and Yu XZ. Essential role of interleukin-12/23p40 in the development of graft-verse-host disease in mice. Biol Bone Marrow Transplant 21(7):1195, 2015.
Li J, Heinrichs J, Haarberg K, Semple K, Veerapathran A, Liu C, Anasetti C, and Yu XZ. HY-specific induced regulatory T cells display high specificity and efficacy in the prevention of acute graft-versus-host disease. J Immunol 195(2):717, 2015.
Zhang L, Ke F, Liu Z, Bai J, Liu J, Yan S, Xu Z, Lou F, Wang H, Zhu H, Sun Y, Cai W, Gao Y, Li Q, Yu XZ, Qian Y, Hua Z, Deng J, Li QJ, and Wang H. MicroRNA-31 negatively regulates peripherally derived regulatory T-cell generation by repressing retinoic acid-inducible protein 3. Nat Commun 6:7639, 2015.
Yan S, Xu Z, Lou F, Zhang L, Ke F, Bai J, Liu Z, Liu J, Wang H, Zhu H, Sun Y, Cai W, Gao Y, Su B, Li Q, Yang X, Yu J, Lai Y, Yu XZ, Zheng Y, Shen N, Chin YE, and Wang H. NF-κB-induced microRNA-31 promotes epidermal hyperplasia by repressing protein phosphatase 6 in psoriasis. Nat Commun 6:7652, 2015.
Wu Y, D Bastian, J Heinrichs, HD Nguyen, J Fu, C Liu, J Jin, QJ Li, C Xia, and Yu XZ. Micro-RNA-17-92 controls T cell responses in graft-versus-host disease and graft-versus-leukemia in mice. Blood, in press.
Schutt S, J Fu, H Nguyen, D. Bastian, J Heinrichs, Y Wu, C Liu, J Pidala, and Yu XZ. Inhibition of BTK and ITK with ibrutinib is effective in the prevention of chronic graft-versus-host disease in mice. Plos One, in press.
Fu J, Y Wu, H Nguyen, J Heinrichs, S Schutt, C Liu, and Yu XZ. T-bet promotes acute graft-versus-host disease through hematopoietic antigen presenting cells in mice. J Immunol, in revision.
Nguyen HD, KM Haarberg, Y Wu, J Fu, J. Heinrichs, D. Bastian, S Schutt, S Chatterjee, S Shrestha, C Liu, S Mehrotra, H Chi, and Yu XZ. Distinct metabolic reprograming of T cells in response to alloantigen after hematopoietic cell transplantation. J Clin Invest, in revision.
Current Research Support
Alloreactive Regulatory T cells Control GVHD and Maintain GVL (PI)
NIH/NCI R01 CA118116
08/01/2006 – 06/30/2016
Elucidating the Function of PKC-theta in Alloreactivity and GVHD (Co-PI)
NIH/NIAID R01 AI082685
06/01/2010 – 05/31/2016
Targeting IL-12/23 p40 Pathways for the Control of GVHD (PI)
NIH/NCI R01 CA169116
03/01/2013 – 02/28/2018
JAK2/STAT3 as a Therapeutic Target and Marker of GVHD (Co-Mentor)
NIH/NHLBI K08 HL116547
7/01/2013 – 6/30/2018
Identification and Validation of T-cell Metabolic Targets for Controlling GVHD and Leukemia Relapse (PI)
NIH/NCI R21 CA192202
2/01/2015 – 1/31/2017
MicroRNA Regulates Graft-versus-Host Disease (PI)
NIH/NIAID R01 AI118305
08/01/2015 – 02/28/2020
South Carolina Center of Economic Excellence Endowed Program (PI)
State of South Carolina