Zhi-Zhang Yang
Zhi-Zhang Yang
Assistant Professor
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Department of Medicine
Mayo Clinic


July 1993 to July 1996 Graduate student, Master degree in Immunology Department of Immunology, Tongji Medical University, Wuhan, Hubei 430030, China
July 1981 to August 1984 Doctor of Medicine Yichang Medical College (now, renamed as Medical College of China Three Gorges University), Yichang, Hubei 440000, China



Dr. Yang's work in tumor immune response has accelerated better understanding of the tumor microenvironment in B-cell non-Hodgkin's lymphoma for hematologists. Some discoveries may have therapeutic potential.

Research Interest

 1.Identification of different types of T cells phenotypically and functionally in B-cell non-Hodgkin's lymphoma. Different types of T cells play completely different roles and positively or negatively impact patient survival. Identifying these different T cell types is the basis for understanding how the immune response looks in B-cell non-Hodgkin's lymphoma.

2.Exploration of cytokine-mediated immune response in B-cell non-Hodgkin's lymphoma. Cytokines are soluble proteins produced by many types of cells and play a crucial role in regulating immune response. Dr. Yang's research is exploring how the immune response is mediated and regulated by cytokines.
3.Determination of interaction between tumor cells and immune cells in the tumor microenvironment. Tumor cells and immune cells coexist in tumor tissue. They interact constantly and adapt to each other. This interaction changes the status of the immune response in tumor patients. Dr. Yang'sresearch is testing how this interaction happens and what mechanism is involved in B-cell non-Hodgkin's lymphoma.

Professional Activities:


Michael A. O’Connor Young Investigator/Travel Award, 3rd Mayo Clinic State of the Art Symposium: Hematological Malignancies. Scottsdale, Arizona. 2006



  1. Novak AJ, Asmann YW, Maurer MJ, Wang C, Slager SL, Hodge LS, Manske M, Price-Troska T, Yang ZZ, Zimmermann MT, Nowakowski GS, Ansell SM, Witzig TE, McPhail E, Ketterling R, Feldman AL, Dogan A, Link BK, Habermann TM, Cerhan. Whole-Exome Analysis Reveals Novel Somatic Genomic Alterations Associated 1 with Outcome in Immunochemotherapy-Treated Diffuse Large B-Cell Lymphoma. Blood Cancer J. 2015 Aug 28; 5:e346. doi: 10.1038/bcj.2015.69.
  2. Xiu B, Lin Y, Grote DM, Ziesmer SC, Gustafson MP, Maas ML, Zhang Z, Dietz AB, Porrata LF, Novak AJ, Liang AB, Yang ZZ (Co-corresponding author), Ansell SM. IL-10 induces the development of immunosuppressive CD14+HLA-DRlow/- monocytes in B-cell non-Hodgkin lymphoma. Blood Cancer J. 2015, Jul 31;5:e328. doi: 10.1038/bcj.2015.56.
  3. Boddicker RL, Kip SN, Xing X, Zeng Y, Yang ZZ, Lee JH, Almada LL, Elsawa SF, Knudson RA, Law ME, Ketterling RP, Cunningham JM, Wu Y, Maurer MJ, O’Byrne MM, Cerhan JR, Slager SL, Link BK, Porcher JC, Grote DM, Jelinek DF, Dogan A, Ansell SM, Fernandez-Zapico ME, Feldman AL. The oncogenic transcription factor IRF4 is regulated by a novel CD30/NF-κB positive feedback loop in peripheral T-cell lymphoma. Blood. 2015; 2015 May 14;125(20):3118-27. doi: 10.1182/blood-2014-05-578575.
  4. Yang ZZ (corresponding author), Grote DM, Ziesmer SC, Xiu B, Novak AJ, Ansell SM. PD-1 expression defines two distinct T-cell sub-populations in follicular lymphoma that differentially impact patient survival. Blood Cancer J. 2015; Feb 20;5:e281. doi: 10.1038/bcj.2015.1.
  5. Asmann YW, Maurer MJ, Wang C, Sarangi V, Ansell SM, Feldman AL, Nowakowski GS, Manske M, Price-Troska T, Yang ZZ, Slager SL, Habermann TM, Cerhan JR, Novak AJ. Genetic diversity of newly diagnosed follicular lymphoma. Blood Cancer J. 2014 Oct 31;4:e256. doi: 10.1038/bcj.2014.80. No abstract available. PMID: 25360902.
  6. Smeltzer JP, Jones JM, Ziesmer SC, Grote DM, Xiu B, Ristow KM, Yang ZZ, Nowakowski GS, Feldman AL, Cerhan JR, Novak AJ, Ansell SM. Pattern of CD14+ follicular dendritic cells and PD1+ T cells independently predicts time to transformation in follicular lymphoma. Clin Cancer Res. 2014 Jun 1;20(11):2862-72. doi: 10.1158/1078-0432.CCR-13-2367. Epub 2014 Apr 11. PMID: 24727328.
  7. Yang ZZ (corresponding author), Grote DM, Xiu B, Ziesmer SC, Price-Troska TL, Hodge LS, Yates DM, Novak AJ, Ansell SM. TGF-β upregulates CD70 expression and induces exhaustion of effector memory T cells in B-cell non-Hodgkin's lymphoma. Leukemia. 2014 Sep;28(9):1872-84. doi: 10.1038/leu.2014.84. Epub 2014 Feb 26. PMID: 24569779.
  8. Hodge LS, Ziesmer SC, Yang ZZ, Secreto FJ, Novak AJ, Ansell SM. Constitutive activation of STAT5A and STAT5B regulates IgM secretion in Waldenstrom's macroglobulinemia. Blood. 2014 Feb 13;123(7):1055-8. doi: 10.1182/blood-2013-08-521963. Epub 2013 Dec 11. PMID: 24335105.
  9. Yang ZZ (corresponding author), Grote DM, Ziesmer SC, Xiu B, Yates NR, Secreto FJ, Hodge LS, Witzig TE, Novak AJ, Ansell SM. Soluble and membrane-bound TGF-beta-mediated regulation of intratumoral T cell differentiation and function in B-cell non-Hodgkin lymphoma. PLoS One. 2013; 8(3):e59456. Epub 2013 Mar 15. PMCID:3598706.
  10. Hodge LS, Ziesmer SC, Yang ZZ, Secreto FJ, Gertz MA, Novak AJ, Ansell SM.  IL-21 in the bone marrow microenvironment contributes to IgM secretion and proliferation of malignant cells in Waldenstrom macroglobulinemia.  Blood. 2012 Nov 1; 120(18):3774-82. Epub 2012 Sep 13.  PMID: 22976953.
  11. Yang ZZ (corresponding author), Grote DM, Ziesmer SC, Niki T, Hirashima M, Novak AJ, Witzig TE, and Ansell SM. IL-12 regulates TIM-3 expression and induces T cell exhaustion in patients with follicular B-cell non-Hodgkin lymphoma. J. Clin. Invest. 2012 Apr 2;122(4):1271-82. doi: 10.1172/JCI59806. Epub 2012 Mar 19. PMID: 22426209.
  12. Ansell SM, Tang H, Kurtin PJ, Koenig PA, Nowakowski GS, Nikcevich DA, Nelson GD, Yang Z, Grote DM, Ziesmer SC, Silberstein PT, Erlichman C, Witzig TE. Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma. Leukemia. 2011 Oct 21. doi: 10.1038/leu.2011.297. [Epub ahead of print]. PMID: 22015775.
  13. Yang ZZ (corresponding author), Grote DM, Ziesmer SC, Manske MK, Witzig TE, Novak AJ, Ansell SM. Soluble IL-2Ralpha facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma. Blood. 2011; 118(10):2809-20. PMID: 21719603.
  14. Yang ZZ, Novak AJ, Ziesmer SC, Witzig TE, and Ansell SM. Malignant B cells skew the balance of regulatory T cells and TH17 cells in B-cell non-Hodgkin's lymphoma. Cancer Res. 2009; 69(13):5522-30. PMID: 19509224.
  15. Wilcox RA, Feldman AL, Wada DA, Yang ZZ, Comfere NI, Dong H, Kwon ED, Novak AJ, Markovic SN, Pittelkow MR, Witzig TE, Ansell SM. B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood. 2009; 114(10):2149-58. PMID: 19597183.
  16. Czesnikiewicz-Guzik M, Lee WW, Cui D, Hiruma Y, Lamar DL, Yang ZZ, Ouslander JG, Weyand CM and Goronzy JJ. T cell subset-specific susceptibility to aging. Clin Immunol. 2008; 127(1): 107-18. PMID: 18222733.
  17. Yang ZZ, Novak AJ, Ziesmer SC, Witzig TE, and Ansell SM. CD70+ Non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25- T cells. Blood. 2007; 110(7): 2537-44. PMID: 17615291.
  18. Lee WW *, Yang ZZ * (* both authors contribute equally to this work), Li G, Weyand CM, and Goronzy JJ. Unchecked CD70 expression on T cells lowers threshold for T cell activation in Rheumatoid Arthritis. J. Immunol. 2007; 179(4): 2609-15. PMID: 17675524.
  19. Yang ZZ, Novak AJ, Ziesmer SC, Witzig TE, and Ansell SM. Attenuation of CD8(+) T-cell function by CD4(+)CD25(+) regulatory T cells in B-cell non-Hodgkin's lymphoma. Cancer Res. 2006; 66(20):10145-52. PMID: 17047079.
  20. Yang ZZ, Novak AJ, Stenson MJ, Witzig TE, and Ansell SM. Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T-cells in B-cell Non-Hodgkin Lymphoma. Blood. 2006; 107(9):3639-46. PMID: 16403912.
  21. Yang ZZ, Zhang AY, Yi FX, Li PL and Zou AP. Redox regulation of HIF-1a levels and HO-1 expression in renal medullary interstitial cells. Am J Physiol Renal Physiol. 2003; 284: F1207-12. PMID: 12595275.
  22. Yang ZZ and Zou AP. Homocysteine enhances TIMP-1 expression and cell proliferation associated with NADH oxidase in rat mesangial cells. Kidney International. 2003; 63: 1012-1020. PMID: 12631082.
  23. Yuan B, Liang M, Yang ZZ, Ruth E, Taylor N, Olivier M and Cowley AW Jr. Gene expression reveals vulnerability to oxidative stress and interstitial fibrosis of the renal outer medulla to nonhypertensive elevations of ANG II.  Am J Physiol Regul Integr Comp Physiol. 2003; 284 (5): R1219-F1230. PMID: 12676744.
  24. Yang ZZ and Zou AP. Transcriptional regulation of heme oxygenases by hypoxia-inducible factor-1a in renal medullary interstitial cells. Am J Physiol Renal Physiol. 2001; 281(5): F900-F908. PMID: 11592948.
  25. Zou AP, Yang ZZ, Li PL and Cowley AW Jr. Oxygen-dependent expression of hypoxia-inducible factor-1a in renal medullary cells of rats. Physiol Genomics. 2001; 6: 159-168. PMID: 11526200.

The followings are published in Chinese with English Abstract

  1. Fang CY, Wu XW, Hang JY, Liu M, Yang ZZ, Liang ZH, Gong FL. Determination of immune reaction of EBV-specific cytotoxic T lymphocytes (CTL) against EBV-LCLs bearing different haplotypes.  Chinese Journal of Immunology. 2001; 17(3): 119-122. (In Chinese)
  2. Wu XW, Jiang XD, Yang ZZ, Gong FL. The C4 Short Gene is More Frequent in Southern Chinese than That in Northern Chinese. Acta Universitatis Medicinae Tongji. 2000; 29(1): 8-10. (In Chinese)
  3. Tu ZK, Wu XW, Liu M, Jiang XD, Yang ZZ, Wu F, Gong FL, Zhao XZ. Association between the feature of the immune response to hepatitis B vaccine and HLA-DRB1 alleles in a Hubei population of the Han nationality. Immunological journal. 2000; 16(1): 45-47. (In Chinese)
  4. Tu ZK, Wu XW, Liu M, Jiang XD, Yang ZZ, Wu W, Gong FL, Zhao XZ. Association between the feature of the immune response to hepatitis B vaccine and HLA class I in Hubei population of the Han nationality. Chinese Journal of Immunology. 1999; 15(1): 20-22. (In Chinese)
  5. Gong FL, Xiong P, Yang ZZ, Xu Y, Jiang XD, Wu XW, Liu M, Wu F, Ferencik S. Liu JY, Grosse-Wilde H. An investigation of the polymorphism of HLA class II alleles in the Han population in Hubei Province of China.  Chinese Journal of Medical Genetics. 1999; 16(4): 216-219. (In Chinese)
  6. Gong FL, Yang ZZ, Xiong P, Xu JZ, Xu Y, Jiang XD, Wu XW, Ferencik S, Liu JY, Grosse-Wilde H. Association between HLA class II (DRB1, DPB1 and DQB1) and Myasthenia gravis in Hubei Han Chinese. Journal of Chinese Pathophysiology. 1999; 15(7): 221. (In Chinese)
  7. Yang ZZ, Wu XW, Jiang XD, Liu M, Wu F, Tu ZK, Gong FL, Zhao XZ. The effect of genetic polymorphism of HLA class I on TNF bioactivity in B lymphoblastoid cell lines. Chinese Journal of Immunology. 1998; 14(4):273. (In Chinese)
  8. Yang ZZ, Liu M, Wu XW, Jiang XD, Wu F, Gong FL, Zhao XZ. Influence of HLA-DRB1 genetic polymorphism on TNF production in B lymphoblastoid cell lines. Immunological Journal. 1998; 14 (3):146. (In Chinese)
  9. Liu M, Wu XW, Wu F, Yang ZZ, Zhao XZ. Simple and practical methods of transforming human B lymphocyte by EB virus. Acta of Tongji Medical University. 1997; 26(4):274. (In Chinese)
  10. Yang Y, Wu XW, Yang ZZ, Wei CH, Liu M, Wu F, Gong FL, Zhao XZ. A research on C4 RFLP of SLE patients of Hubei Han Nationality. Chinese Journal of Immunology. 1997; 13(2):112. (In Chinese)
  11. Yang ZZ, Wu XW, Wu F, Jiang XD, Liu M, Zhang WJ, Dawkins RL, Zhao XZ. RFLP of HLA central region revealing the genetic conservation of HLA haplotype. Immunological Journal. 1996; 12(2):96. (In Chinese)
  12. Yang ZZ, Wu XW, Gong FL. TNF genetic polymorphism in auto-immune diseases. Foreign Medical Science-Immunology. 1995; 6:309. (In Chinese)
  13. Yang ZZ, Wu XW, Zhao XZ. Association between HLA class II (DRB, DPB1 and DQB1) and SLE patients. Immunological Journal. 1995; 11(4): 275. (In Chinese)


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