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Department of Microbiology and Immunology

Xue-Zhong Yu, MD

Dr. Yu PictureProfessor

Department of Microbiology & Immunology
Department of Medicine
Distinguished Endowed Chair
SmartState Cancer Stem Cell Biology & Therapy Program
Medical University of South Carolina

Education
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.

Contact Info
Email: yux@musc.edu
Phone: (843) 792-4756
Office: HCC HO350
Lab: HCC HO356

Research Interests

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. 

Recent Publications

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 rapamycinBlood 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 XZAbundant 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 XZT 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 miceBiol 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 XZPrevention 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 andAnasetti 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 XZLBH589 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 XZAdoptive 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 XZC-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 diseaseBlood 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 activationEur J Immunol, in press.

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, in press. 

Current Research Support

Alloreactive Regulatory T cells Control GVHD and Maintain GVL

NIH/NCI
 R01 CA118116

08/01/2006 – 06/30/2016

Elucidating the Function of PKC-theta in Alloreactivity and GVHD

NIH/NIAID
 R01 AI082685

06/01/2010 – 05/31/2015

Targeting IL-12/23 p40 Pathways for the Control of GVHD

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
NIH/NCI
 R21 CA192202

2/01/2015 – 1/31/2017

South Carolina Center of Economic Excellence Endowed Program
State of South Carolina
05/2013 -

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