唐宏

1984-09--1988-07 南京大學 學士

1988-09--1990-12 中國科學院微生物研究所 碩士

1991-01--1996-05 Rutgers University-New Jersey State University 博士 ^[1] 

1996-06~1999-12,Massachusetts Institute of Technology，博士後

2000-01~2000-10,美國杜邦醫藥公司，高級研究員

2001-2005 中國科學院微生物研究所分子免疫學中心 研究員，主任

2005-2012 中國科學院生物物理研究所感染免疫中心 研究員，主任

2006-2009 生物大分子國家重點實驗室 副主任

2007年起 科技部國家級國際聯合研究中心 主任

2009-2012 中科院感染免疫重點實驗室 主任 ^[1] 

2012-04~2015-12, 中國科學院武漢病毒研究所，副所長 ^[2-3] 

2015-12~2022-04, 中國科學院上海巴斯德研究所，所長 ^[4-5] 

2019-04-10-今,中國細胞生物學會, 常務理事

2016-06-07-今,中國細胞學會免疫細胞分會, 會長

2016-05-06-今,巴斯德國際研究網絡（亞太區）, 負責人

2010-04-28-2015-12-30,中國免疫學會青年免疫學者工作委員會, 主任

2005-01-01-今,中國免疫學會, 常務理事 ^[1] 

主要從事淋巴細胞發育過程中的信號轉導機制，病毒感染的天然免疫調控機理等研究。 ^[6] 

（一）：天然免疫反應：巨噬細胞和樹突狀細胞TLR/RLR受體介導的I/III型干擾素應答反應是機體控制病毒複製與擴散所必需的天然免疫反應。我們實驗室在以下幾方面做出原創性工作：宿主SUMO修飾是激活RLR（RIG-I和Mda5），產生I型干擾素所必需的(Protein & Cell, 2011)；我們原創性發現了冠狀病毒和乙肝病毒均編碼去泛素化酶，抑制I/III型干擾素應答反應的關鍵受體RIG-I或關鍵轉錄因子IRF3活化過程的磷酸化反應(Cell Research, 2008; Protein & Cell, 2011)，逃逸宿主細胞的天然免疫防禦系統。在我們實驗室首創的反映丙型肝炎病毒(HCV)感染自然史和免疫病理的小鼠模型中(Cell Research, 2014)，我們發現HCV感染上調NK細胞抑制性受體NKG2A，導致NK細胞功能耗竭，是HCV建立持續性感染的主要原因(Nature Communications, 2018)。更重要的是，NK細胞耗竭是導致CD8+細胞毒性細胞（CTL）耗竭的誘因，抗體阻斷NKG2A或其配體Qa-1，可以復甦NK跟CTL殺傷功能，終止HCV感染。因此，NKG2A是慢性病毒感染的免疫卡點(checkpoint)。相關的發現在癌症免疫中也得到了映證。而在針對革蘭氏陰性菌感染的腸炎研究中，我們率先發現表觀遺傳因子Baf180是抑制腸炎炎性因子TNFα表達的關鍵轉錄因子(Nature Microbiology, 2017)，以及巨噬細胞中醛糖還原酶產生並釋放的糖醇，是啓動全身天然免疫反應的信使小分子/警報素(Cell Microbe & Host, 2019)。

（二）適應性免疫反應：病毒、細菌等感染性膿毒血癥常伴隨胸腺急劇萎縮，CD4+ T細胞減少(CD4 T lymphopenia),但相關免疫病理機制一直不清楚。我們率先發現，T細胞是抑制炎性風暴所必需的，且足夠的T細胞數量是機體控制炎性反應、降低死亡率的前提條件(Nature Medicine, 2007; PNAS, 2008)。更有意思的，T細胞在天然免疫反應階段行使的這種負調節作用，並不需要病原特異性的T細胞受體(TCR)。因此，T細胞在進化過程中仍保留了抗原非特異性的天然免疫細胞特徵。這種天然免疫樣T細胞功能，還在高血壓引起的心肌損傷中發揮先決性作用(Journal of Immunology, 2014)。

實驗室主要從事的研究工作已發表高水平論文60多篇（Cell, Nat Med, Nat Immunol, Nat Microbiology, Nat Communs, Immunity, Cell Host & Microbe, Cell Res, Genes & Dev, PNAS等）。 ^[6] 

1991-1994年 新澤西州細胞與分子生物學基金資助

1996-2000年 Irvington Institute of Immunology 研究基金

2000-2003年 中國科學院海外傑出人才引進計劃“百人計劃”

2001-2004年 基金委“國家傑出青年” 基金資助

2007-2009年 江蘇省高層次創新創業人才基金

2008年 國務院政府特殊津貼

2009年 談家楨生命科學創新獎

2009年 新世紀百千萬人才工程國家級人選

2010年 中國科學院優秀研究生指導教師獎

2011年 北京市科學技術獎一等獎（第一完成人）

2012年 第四屆中國僑界貢獻獎（創新團隊）“重要病毒感染的免疫應答與調節機制” （負責人）

2018年 上海市領軍人才 ^[6] 

（ 1 ） 丙型肝炎病毒感染及防治的基礎研究, 主持, 國家級, 2011-01--2013-08

（ 2 ） HBV/HCV病毒感染免疫的機理和疫苗研究, 主持, 部委級, 2007-01--2011-12

（ 3 ） 胸腺退化的規律、意義及發生機制, 參與, 國家級, 2010-10--2016-09

（ 4 ） 炎症小體（inflammasome）介導的急性肝損傷機制研究, 參與, 國家級, 2011-01--2015-12

（ 5 ） 建立艾滋病、手足口病和丙型肝炎等動物模型, 主持, 市地級, 2012-01--2015-12

（ 6 ） 人感染H7N9禽流感疫情研究, 參與, 部委級, 2013-05--2014-12

（ 7 ） 肥胖症的腸道生態免疫學調節機制, 主持, 國家級, 2013-01--2017-12

（ 8 ） 埃博拉病毒感染的免疫病理研究, 主持, 國家級, 2015-07--2017-12

（ 9 ） 病毒性肝炎誘發肝癌的炎症調控機制, 主持, 部委級, 2017-01--2019-12

（ 10 ） 丙型肝炎病理進展和糖代謝紊亂丙肝肝外疾病的發病機制研究, 參與, 部委級, 2017-01--2019-12

（ 11 ） 慢性丙肝免疫耗竭機制和丙肝病毒清除策略研究, 主持, 部委級, 2017-05--2022-04

（ 12 ） 丙型肝炎病毒持續感染的免疫調節機制研究, 主持, 國家級, 2016-01--2020-12

2013年 中國專利《一種CD81和OCLN雙轉基因小鼠的構建方法和用途》專利號：ZL2013 1 0502450.6

2015年 美國專利《CD81 AND OCLN DOUBLE TRANSGENIC MOUSE AND ITS CONSTRUCTION METHODS》專利號：US2015/0113673 AI

2017年 歐洲專利《A METHOD FOR CONSTRUCTING A CD81 AND OCLN DOUBLE TRANSGENIC MOUSE》專利號：14189856.9

2019年 中國專利《靶向NK細胞免疫檢查點治療感染性疾病的方法》專利號：201910219951.0

2020年 中國專利《用於胚胎或生殖細胞移植的二元控制儀器》專利號：ZL 2019 2 2088990.X ^[6] 

1， B 細胞發育， 《分子細胞生物學》， 陳燁光，張傳茂，陳全 主編， 第22章， pp414-426，清華大學出版社，北京，2006年9月第一版，2011年第二版

2， 胸腺和T細胞發育，《分子細胞生物學》， 陳燁光，張傳茂，陳全 主編， 第23章， pp427-440，清華大學出版社，北京，2006年9月第一版，2011年第二版

3， 炎症性細胞因子與疾病，《免疫學前沿進展》，曹雪濤 主編，第19章，人民衞生出版社，北京，2009年（第一版），2011年（第二版） ^[6] 

1. Tang H, Severinov K, Goldfarb A, Fenyo D, Chait B, and Ebright R. (1994) Location, structure and function of the target of a transcription activator protein. Genes & Dev. 8, 3058-3067.

2. Blatter E, Ross W, Tang H, Gourse R, and Ebright R. (1994) Domain organization of RNA polymerase a subunit: C-terminal 85 amino acid constitute a domain capable of dimerization and DNA binding. Cell 78, 889-896.

3. Tang H, Severinov K., Goldfarb A and Ebright R. (1995) Rapid RNA polymerase genetics: one-day, no-column preparation of reconstituted recombinant Escherichia coli RNA polymerase. Proc. Natl. Acad. Sci. USA 92, 4902-4906.

4. Ebright RH, Tang H, Blatter E, Severinov K, Goldfarb A, Ross W and Gourse R. (1995) Location, structure, and function of the target of a transcription activator protein. FASEB J. 9 (6), 1321.

5. Tang H, Sun X, Reinberg D, and Ebright R. (1996) Protein-protein interactions in eukaryotic transcription initiation: structure of the pre-initiation complex. Proc. Natl. Acad. Sci. USA 93, 1119-1124.

6. Tang H, Kim Y, Severinov K, Goldfarb A, and Ebright R. (1996) Escherichia coli RNA polymerase: rapid reconstitution from recombinant a, b, b’ and s subunits. Methods Enzymol. 273, 130-134.

7. Gaal T, Ross W, Blatter EB, Tang H, Jia X, Krishnan VV, Assa-Munt N, Ebright RH and Gourse R (1996) DNA binding determinants of the a subunit of RNA polymerase: a novel DNA binding domain architecture. Genes & Dev.10, 16-26.

8. Heyduk T, Ma Y, Tang H, Ebright R. (1996) Fluorescence Anisotropy: Rapid, quantitative assay for protein-DNA and protein-protein interaction. Methods Enzymol.274, 492-503.

9. Heyduk T, Heyduk E, Severinov K, Tang H, and Ebright R (1996) Rapid epitope mapping by hydroxyl-radical protein footprinting: Determinants of RNA polymerase alpha subunit for interaction with beta, beta’ and sigma subunits. Proc. Natl. Acad. Sci. USA 93,10162-66.

10. Jia X, Krishana VV, Gaal T, Ross W, Blatter E, Tang H, Ebright RH, Gourse RL and Assamunt N (1996) DNA-binding determinants of the alpha-subunit of RNA polymerase-A novel DNA binding domain architecture. Biophys. J. 70 (2), SU481.

11. Langrange T, Kapanidis, AN, Tang H, Reinberg D and Ebright RH (1998) New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor IIB. Genes & Dev. 12, 34-44.

12. Tang H and Sharp PA (1999) Transcriptional regulation of the murine 3' IgH enhancer by Oct-2. Immunity 11, 517-26.

13. He HZ, Ding Y, Bartlam M, Sun F, Le Y, Qin XC, Jiang F, Liu YW, Tang H, Liu JY, Zhao NM and Rao ZH (2003) Mechanism for b-lactam and protein acetylation revealed by the crystal structure of Tabtoxin Resistance protein, a GCN5-related N-acetyltransferase, complexed with acetyl coenzyme A. J Mol Biol. 325, 1019–1030

14. Chen H, Tang H and Ebright RH (2003) Functional Interaction between RNA Polymerase α subunit C-Terminal Domain and б⁷⁰ UP-Element-and Activator-Dependent Transcription. Mol Cell，11(6):1621-33.

15. Zheng Y, Shi Y, Tian C, Jiang C, Jin H, Chen J, Almasan A, Tang H and Chen H (2004) Essential Role of the Voltage-dependent Anion Channel (VDAC) in Mitochondrial Permeability Transition Pore Opening and Cytochrome C Release Induced by Arsenic Trioxide. Oncogene, 23:1239-47.

16. Kang X, Xu Y, Wu X, Liang Y, Wang C, Guo J, Wang Y, Chen M, Wu D, Wang Y, Bi S, Qiu Y, Lu P, Cheng J, Xiao B, Hu L, Gao X, Liu J, Wang Y, Song Y, Zhang L, Suo F, Chen T, Huang Z, Zhao Y, Lu H, Pan C and Tang H (2005) Proteomic Fingerprints for Potential Application to Early Diagnosis of Severe Acute Respiratory Syndrome. Clin Chem 51(1): 56-64.

17. Weng C, Li Y, Xu D, Shi Y, Tang H (2005) Specific cleavage of Mcl-1 by caspase-3 in TRAIL- induced apoptosis in Jurkat leukemia T cells. J Biol Chem, 280:(11) 10491–10500.

18. Perry AK, Chen G, Zheng DH, Tang H and Cheng G (2005) The host type I interferon response to viral and bacterial infections. Cell Res, 15(6):407-422.

19. Zheng Y, Yamaguchi H, Tian C, Lee M, Tang H, Wang H and Chen Q (2005) Arsenic trioxide (As₂O₃) induces apoptosis through activation of Bax in hematopoietic cells. Oncogene, 24(20):3339-47.

20. Qin X and Tang H (2006) Differential regulation of chromatin structure of the murine 3’ IgH enhancer and IgG2b germline promoter in response to lipopolysaccharide and CD40 signaling. Mol Immunol 43:1211–20.

21. Chen J, Chen L, Wang G and Tang H (2007) Cholesterol-dependent and independent CD40 internalization and signaling activation in cardiovascular endothelial cells. Arterioscler Thromb Vasc Biol, 27:2005-2013.

22. Kim K, Zhao J, Auh S, Yang X, Du P, Tang H*, and Fu Y* (2007) Adaptive immune cells temper initial innate responses. Nature Med 13(10):1248-1252 (*co-correspondence).

23. Pan L, Chen S, Weng C, Call G, Zhu D, Tang H, Zhang N and Xie T (2007) Stem Cell Aging Is Controlled Both Intrinsically and Extrinsically in the Drosophila Ovary. Cell Stem Cell, 1:458-469.

24. Zhao J, Kim KD, Yang X, Auh S, Fu YX* and Tang H* (2008) Hyper innate responses in neonates lead to increased morbidity and mortality after infection. Proc Natl Acad Sci U S A 105(21):7528-33 (*co-correspondence).

25. Zheng D, Chen G, Guo B, Cheng G* and Tang H* (2008) PLP2, a potent deubiquitinase from murine hepatitis virus, strongly inhibits cellular type I interferon production. Cell Res, 18:1105–13 (*co-correspondence).

26. Deng W, Shi M, Han M, Zhong J, Li Z, Li W, Hu Y, Yan L, Wang J, He Y, Tang H, Deubel V, Luo X, Ning Q, Sun B (2008) Negative regulation of virus-triggered IFN-beta signaling pathway by alternative splicing of TBK1. J Biol Chem. 283(51):35590-7.

27. Zhao J, Yang X, Kim KD, Auh S, Fu YX* and Tang H* (2009) Do adaptive immune cells suppress or activate innate immunity? Trends Immunol. 30(1):8-12 (*co-correspondence).

28. Li X, Yang X, Xu Y, Jiang X, Li X, Nan F, Tang H. (2009) Troglitazone inhibits cell proliferation by attenuation of epidermal growth factor receptor signaling independent of peroxisome proliferator-activated receptor gamma. Cell Res. 19(6):669-71.

29. Yu J, Pan L, Qin X, Chen H, Xu Y, Chen Y, Tang H. (2010) MTMR4 Attenuates Transforming Growth Factor β (TGFβ) Signaling by Dephosphorylating R-Smads in Endosomes. J Biol Chem, 285(11):8454–8462.

30. Mi Z, Fu J, Xiong Y and Tang H. (2010) SUMOylation of RIG-I positively regulates the type I interferon signaling. Protein Cell, 1(3):275-283.

31. Tang H and Fu Y (2010) A new role for T cells in dampening innate inflammatory responses. Sci China Life Sci., 53(2):190-4.

32. Jiang J, Tang H. (2010) Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein. Protein Cell. 1(12):1106-17.

33. Fu J, Xiong Y, Xu Y, Cheng G and Tang H. (2011) MDA5 is SUMOylated by PIAS2β in the upregulation of Type I interferon signaling. Mol Immunol. 48(4):415-22 (Epub 2010 Dec 14).

34. Da Q, Yang X, Xu Y, Gao G, Cheng G, Tang H. (2011) TANK-Binding Kinase 1 Attenuates PTAP-Dependent Retroviral Budding through Targeting Endosomal Sorting Complex Required for Transport-I. J Immunol. 186(5):3023-30 (Epub 2011 Jan 26).

35. Wang G, Chen G, Zheng D, Cheng G, Tang H (2011) PLP2 of Mouse Hepatitis Virus A59 (MHV-A59) Targets TBK1 to Negatively Regulate Cellular Type I Interferon Signaling Pathway. PLoS ONE, 6(2): e17192. doi:10.1371/journal.pone.0017192.

36. Wang X, Pan L, Wang S, Zhou J, McDowell W, Park J, Haug J, Staehling K, Tang H, Xie T. (2011) Histone H3K9 trimethylase Eggless controls germline stem cell maintenance and differentiation. PLoS Genet. 7(12):e1002426. Epub 2011 Dec 22.

37. Zhang X, Angkasekwinai P, Dong C and Tang H (2011) Structure and function of interleukin-17 family cytokines. Protein Cell, 2(1):26-40.

38. Upadhyay V, Poroyko V, Kim T, Devkota S, Fu S, Liu D, Tumanov AV, Koroleva EP, Deng L, Nagler C, Chang EB, Tang H & Fu YX (2012) Lymphotoxin regulates commensal responses to enable diet-induced obesity. Nat Immunol 13(10):947-53.

39. Yu J, He X, Chen YG, Hao Y, Yang S, Wang L, Pan L, Tang H (2013)Myotubularin-related Protein 4 (MTMR4) Attenuates BMP/Dpp Signaling by Dephosphorylation of Smad Proteins. J Biol Chem. 288(1):79-88.

40. Wu A, Su C, Wang D, Peng Y, Liu M, Hua S, Li T, Gao GF, Tang H, Chen J, Liu X, Shu Y, Peng D, Jiang T.(2013) Sequential reassortments underlie diverse influenza H7N9 genotypes in China. Cell Host Microbe.14(4):446-52.

41. Wang XX, Ying P, Diao F, Wang Q, Ye D, Jiang C, Shen N, Xu N, Chen WB, Lai SS, Jiang S, Miao XL, Feng J, Tao WW, Zhao NW, Yao B, Xu ZP, Sun HX, Li JM, Sha JH, Huang XX, Shi QH, Tang H, Gao X, Li CJ. (2013) Altered protein prenylation in Sertoli cells is associated with adult infertility resulting from childhood mumps infection. J Exp Med.210(8):1559-74.

42. Ma F, Feng J, Zhang C, Li Y, Qi G, Li H, Wu Y, Fu Y, Zhao Y, Chen H, Du J, Tang H. (2014) The requirement of CD8+ T cells to initiate and augment acute cardiac inflammatory response to high blood pressure. J Immunol, 192(7):3365-73

43. Chen J, Zhao Y, Zhang C, Chen H, Feng J, Chi X, Pan Y, Du J, Guo M, Cao H, Chen H, Wang Z, Pei R, Wang Q, Pan L, Niu J, Chen X, Tang H. (2014) Persistent hepatitis C virus infections and hepatopathological manifestations in immune-competent humanized mice. Cell Res. Sep;24(9):1050-66.

44. Yang Z, Du J, Chen G, Zhao J, Yang X, Su L, Cheng G, Tang H. (2014) Coronavirus MHV-A59 infects the lung and causes severe pneumonia in C57BL/6 mice. Virol Sin. 29(6):393-402

45. Pan L, Wang S, Lu T, Weng C, Song X, Park JK, Sun J, Yang ZH, Yu J, Tang H, McKearin DM, Chamovitz DA, Ni J, Xie T. (2014) Protein competition switches the function of COP9 from self-renewal to differentiation. Nature. 514(7521):233-6.

46. Chen J, Wang N, Dong M, Guo M, Zhao Y, Zhuo Z, Zhang C, Chi X, Pan Y, Jiang J, Tang H, Niu J, Yang D, Li Z, Han X, Wang Q, Chen X. (2015) The Metabolic Regulator Histone Deacetylase 9 Contributes to Glucose Homeostasis Abnormality Induced by Hepatitis C Virus Infection. Diabetes. 64(12):4088-98

47. Yang Y and Tang H. (2016) Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia. Cell Mol Immunol. 13(4):432-42.

48. X He, J Yu, M Wang, Y Cheng, Y Han, S Yang, G Shi, L Sun, Y Fang, S Gong, Z Wang, YX Fu, L Pan and H Tang (2017) Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune response in Drosophila and mice. Nature Microbiology, 2:17056

49. Wang Z, Gao Y, Zhang C, Hu H, Guo D, Xu Y, Xu Q, Zhang W, Deng S, Lv P, Yang Y, Ding Y, Li Q, Weng C, Chen X, Gong S, Chen H, Niu J, Tang H. (2017) Quinolinate Phosphoribosyltransferase is an Antiviral Host Factor Against Hepatitis C Virus Infection. Sci Rep, 7(1):5876.

50. Zhang C, Feng J, Du J, Zhuo Z, Yang S, Zhang W, Wang W, Zhang S, Iwakura Y, Meng G, Fu YX, Hou B, Tang H.(2017) Macrophage-derived IL-1α promotes sterile inflammation in a mouse model of acetaminophen hepatotoxicity. Cell Mol Immunol. doi: 10.1038/cmi.2017.22.

51. Fu W, Liu X, Lin X, Feng H, Sun L, Li S, Chen H, Tang H, Lu L, Jin W, Dong C.(2018) Deficiency in T follicular regulatory cells promotes autoimmunity. J Exp Med, 215(3):815-825.

52. Zhang H, Zhang C, Tang H, Gao S, Sun F, Yang Y, Zhou W, Hu Y, Ke C, Wu Y, Ding Z, Guo L, Pei R, Chen X, Sun Sy M, Zhang B, Li C. (2018) CD2-associated Protein Contributes to Hepatitis C Virus Propagation and Steatosis by Disrupting Insulin Signaling. Hepatology. doi: 10.1002/hep.30073.

53. Y Zhang, T Kim, JA Wroblewska, V Tesic, V Upadhyay, RR Weichselbaum, AV Tumanov, H Tang, X Guo, HD Tang & YX Fu (2018) Type 3 innate lymphoid cell-derived lymphotoxin prevents microbiota-dependent inflammation. Cell Mol Immunol, 15:697–709.

54. S Hong, Z Zhang, H Liu, M Tian, X Zhu, Z Zhang, W Wang, X Zhou, F Zhang, Q Ge, B Zhu, H Tang*, Z Hua* and B Hou* (2018) B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4+ T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen. Immunity, 49:695-708. (*co-correspondence)

55. C Zhang, X Wang, S Li, T Twelkmeyer, W Wang, S Zhang, S Wang, J Chen, X Jin, Y Wu, X Chen, S Wang, J Niu, H Chen and H Tang (2019) NKG2A is a NK cell exhaustion checkpoint for HCV persistence. Nat Communs, 10: 1507.

56. Yang S, Zhao Y, Yu J, Fan Z, Gong ST, Tang H*, Pan L*. (2019) Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila. Cell Host & Microbe. 14;26(2):240-251.e8. (*co-correspondence)

57. Deng S, Sun Z, Qiao J, Liang Y, Liu L, Dong C, Shen A, Wang Y, Tang H*, Fu YX*, Peng H*. (2020) Targeting tumors with IL-21 reshapes the tumor microenvironment by proliferating PD-1^intTim-3^-CD8⁺ T cells. JCI Insight. Apr 9;5(7). pii: 132000. doi: 10.1172/jci.insight.132000 (*co-correspondence).

58. Zhang, C., Wang, F., Silvestre, J., Arenzana-Seisdedos F. & Tang H. (2020) Is aberrant CD8+ T cell activation by hypertension associated with cardiac injury in severe cases of COVID-19?. Cell Mol Immunol.

59. X Lin, T Twelkmeyer, S Wang, R Xu, FS Wang, C Zhang, H Tang (2020) An Immunopathogenic Perspective of interleukin-1 Signaling. Cell Mol Immunol. May 28. doi: 10.1038/s41423-020-0475-y.