首页 > 科学研究 > 基因和免疫治疗研究课题组

> 课题组简介

  本课题组的主要研究方向是血液病的基因治疗和免疫治疗研究。结合应用基因组编辑技术和造血干细胞分化技术探索血友病的基因治疗新途径,同时应用嵌合抗原受体T细胞(CAR-T)等技术探索白血病靶向治疗的新型细胞免疫疗法。目前,在血友病的基因治疗及出凝血研究方面已积累丰富的经验,利用腺相关病毒和慢病毒制备平台建立了靶向肝细胞和血小板的基因治疗技术,并在动物实验中对基因治疗的疗效和安全性进行验证。此外,课题组致力于建立符合国际一流标准的细胞免疫治疗GMP实验室,为CAR-T这种新兴免疫治疗方法的科学研究以及临床试验研究,提供理论依据和实践经验。

> 课题组长:王月英 章国卫


> 代表性论文

1.Xu J, Wang YY*, Dai YJ, Zhang W, Zhang WN, Xiong SM, Gu ZH, Wang KK, Zeng R, Chen Z, Chen SJ. DNMT3A Arg882 mutation drives chronic myelomonocytic leukemia through disturbing gene expression/DNA methylation in hematopoietic cells. Proc Natl Acad Sci USA. 2014. 111(7):2620-2625.

2.Zhao LJ, Wang YY, Li G, Ma LY, Xiong SM, Weng XQ, Zhang WN, Wu B, Chen Z, Chen SJ. Functional features of RUNX1 mutants in acute transformation of chronic myeloid leukemia and their contribution to inducing murine full-blown leukemia. Blood. 2012. 119(12):2873-2882.

3.Chen B, Wang YY, Shen Y, Zhang WN, He HY, Zhu YM, Chen HM, Gu CH, Fan X, Chen JM, Cao Q, Yang G, Jiang CL, Weng XQ, Zhang XX, Xiong SM, Shen ZX, Jiang H, Gu LJ, Chen Z, Mi JQ, Chen SJ. Newly diagnosed acute lymphoblastic leukemia in China (I): Abnormal genetic patterns in 1346 childhood and adult cases and their comparison to the reports from Western countries. Leukemia. 2012. 26: 1608-1616.

4.Wang YY, Zhao LJ, Wu CF, Liu P, Shi L, Liang Y, Xiong SM, Mi JQ, Chen Z, Ren R, Chen SJ. C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci U S A. 2011. 108 (6): 2450-2455.

5.Pan MM, Zhang QY, Wang YY, Liu P, Ren RB, Huang JY, Chen LT, Xi XD, Chen Z, Chen SJ. Human NUP98-IQCG fusion protein induces acute myelomonocytic leukemia in mice by dysregulating the Hox/Pbx3 pathway. Leukemia 2015 doi: 10.1038.

6.Xu L, Gu ZH, Li Y, Zhang JL, Chang CK, Pan CM, Shi JY, Shen Y, Chen B, Wang YY, Jiang L, Lu J, Xu X, Tan JL, Chen Y, Wang SY, Li X, Chen Z, Chen SJ. Genomic landscape of CD34+ hematopoietic cells in myelodysplastic syndrome and gene mutation profiles as prognostic markers. Proc Natl Acad Sci USA 2014; 111:8589-8594

7.Chen WL, Wang JH, Zhao AH, Xu X, Wang YH, Chen TL, Li JM, Mi JQ, Zhu YM, Liu YF, Wang YY, Jin J, Huang H, Wu DP, Li Y, Yan XJ, Yan JS, Li JY, Wang S, Huang XJ, Wang BS, Chen Z, Chen SJ, Jia W. A distinct glucose metabolism signature of acute myeloid leukemia with prognostic value. Blood 2014; 124:1645-1654.

8.Zhen T, Wu CF, Liu P, Wu HY, Zhou GB, Lu Y, Liu JX, Liang Y, Li KQ, Wang YY, Xie YY, He MM, Cao HM, Zhang WN, Chen LM, Petrie K, Chen SJ, Chen Z. Targeting of AML1-ETO in t(8;21) leukemia by oridonin generates a tumor suppressor-like protein. Science Translational Medicine 2012; 4:127-138.

9.Baumgartner CK, Zhang G, Kuether EL, Weiler H, Shi Q, Montgomery RR. Comparison of platelet-derived and plasma factor VIII efficacy using a novel native whole blood thrombin generation assay. J Thromb Haemost. 2015 Dec;13(12):2210-9.

10.Chen Y, Schroeder JA, Kuether EL, Zhang G, Shi Q. Platelet Gene Therapy by Lentiviral Gene Delivery to Hematopoietic Stem Cells Restores Hemostasis and Induces Humoral Immune Tolerance in FIX Mice. Mol Ther. 2014 Jan;22(1):169-77.

11.Cao HM*, Wang ZY*, Zhang GW*, Liu CF, Pan CM, Zhao SX, Song ZY, Song HD*, Zhang L. Identification of a locus (DSP2) for disseminated superficial porokeratosis at chromosome 12q21.2-24.21. Clin Exp Dermatol.;37(6):672-6; 2012 Aug.

12.Jun-Hua Ma*, Shu-Hong Shen*, Guo-Wei Zhang*, Dong-Sheng Zhao, Chao Xu, Chun-Ming Pan, He Jiang, Zhi-Quan Wang, Huai-Dong Song. Identification of a locus for autosomal dominant high myopia on chromosome 5p13.3-p15.1 in a Chinese family. Molecular Vision. 2010 Oct 12;16:2043-54 .

13.Zhang G, Shi Q, Fahs SA, Kuether EL, Walsh CE, Montgomery RR. Factor IX ectopically expressed in platelets can be stored in α-granules and corrects the phenotype of hemophilia B mice. Blood 2010 Aug 26;116(8):1235-43.

14.Song HD*, Tu CC*, Zhang GW*, Wang SY, Zheng K, Lei LC, Chen QX, Gao YW, Zhou HQ, Xiang H, Zheng HJ, Chern SW, Cheng F, Pan CM, Xuan H, Chen SJ, Luo HM, Zhou DH, Liu YF, He JF, Qin PZ, Li LH, Ren YQ, Liang WJ, Yu YD, Anderson L, Wang M, Xu RH, Wu XW, Zheng HY, Chen JD, Liang G, Gao Y, Liao M, Fang L, Jiang LY, Li H, Chen F, Di B, He LJ, Lin JY, Tong S, Kong X, Du L, Hao P, Tang H, Bernini A, Yu XJ, Spiga O, Guo ZM, Pan HY, He WZ, Manuguerra JC, Fontanet A, Danchin A, Niccolai N, Li YX, Wu CI, Zhao GP. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human. Proc Natl Acad Sci U S A. 2005, Feb 15; 102(7):2430-5.

15.Song HD*, Sun XJ*, Deng M*, Zhang GW*, Zhou Y, Wu XY, Sheng Y, Chen Y, Ruan Z, Jiang CL, Fan HY, Zon LI, Kanki JP, Liu TX, Look AT, Chen Z. Hematopoietic gene expression profile in zebrafish kidney marrow. Proc Natl Acad Sci U S A. 2004, Nov 16; 101(46):16240-16245.

16.The Chinese SARS Molecular Epidemiology Consortium. Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China. Science 2004, 303(5664): 1666~1669.

17.Zhang R, Wang Q, Zhang L, Chen S. Optimized human factor IX expression cassettes for hepatic directed gene therapy of hemophilia B. Front Med. 2015 Mar; 9(1): 90-9.

18.Carbonaro DA (co-1st author), Zhang L (co-1st author), X Jin, Montiel-Equihua C, Geiger S, Carmo M. Pre-clinical demonstration of lentiviral vector mediated correction of immunological and metabolic abnormalities in models of adenosine deaminase deficiency. Mol Ther. 2013 Nov 20.

19.Zhang L, Thrasher AJ, Gaspar HB. Current progress on gene therapy for primary immunodeficiencies. Gene Ther. 2013 Oct; 20(10):963-9.

20.Montiel-Equihua CA, Zhang L, Knight S, Saadeh H, Scholz S, Carmo M, Alonso-Ferrero ME, Blundell MP, Monkeviciute A, Schulz R, Collins M, Takeuchi Y, Schmidt M, Fairbanks L, Antoniou M, Thrasher AJ, Gaspar HB. The β-globin locus control region in combination with the EF1α short promoter allows enhanced lentiviral vector-mediated erythroid gene expression with conserved multilineage activity. Mol Ther. 2012 Jul; 20(7):1400-9.

21.Drissen R, Guyot B, Zhang L, Aztberger A, Sloane-Stanley J, Wood W, Porcher C, and Vyas P. Combinatorial action of two upstream enhancers regulates erythroid Gata1 expression. Blood. 2010 Apr 29; 115(17):3463-71.

22.Zhang L, Yang SH, Sharrocks AD. Rev7/MAD2B links c-Jun N-terminal protein kinase pathway signalling to activation of the transcription factor Elk-1. Mol Cell Biol. 2007 Apr; 27(8):2861-9.