国际感染与免疫研究 主任 Philipp Lang教授

作者:2017/05/23 01:35

Philipp A. Lang教授,博导,苏州大学讲座教授

Philipp A. Lang 曾在德国图宾根大学、瑞士苏黎世大学和美国耶鲁大学进行医学专业训练。并取得德国图宾根大学的医学博士学位(M.D)。在医学博士后阶段,他加入了诺贝奖得主Rolf Zinkernagel教授在瑞士苏黎世大学的实验室,主要研究免疫系统对抗病毒和细菌的机理。之后又加入了世界知名华裔科学家麦德华教授和Pamela Ohsahi教授的位于加拿大多伦多大学实验室,继续从事免疫系统研究,并最终获得自然哲学博士学位(Ph.D)。

20102014 年间,Lang博士被聘为杜塞尔多夫大学医学院消化道疾病系首席研究员。2014年起 Lang博士被聘为杜赛尔多夫大学终身教授(W3)并成为分子医学二系的系主任。他目前的主要研究方向是病毒性肝炎(例如乙肝病毒和丙肝病毒)引起的免疫反应方面研究。利用啮齿类动物模型,Lang教授致力于发现可以提高自身免疫功能的未知免疫因子以对抗病毒以及癌症。Lang 教授的研究成果获得了洪堡基金会的Sofja Kovalevskaja(德国最有影响力的科学奖之一)以及图宾根大学杰出医生奖,德国生理学学会Du Bois Reymond。至今,Lang教授的研究成果已在高级别SCI期刊发表90多篇学术论文,包括Nature, Science, Cell, Immunity, Nature medicine, Nature immunology, J Exp Med, J Clin Inest, Proc Natl Acad Sci USA 等顶尖权威杂志。并申请了3个专利。

近五年代表性论文:

1. Mak TW, Grusdat M, Duncan GS, Dostert C, Nonnenmacher Y, Cox M, Binsfeld C, Hao Z, Brüstle A, Itsumi M, Jäger C, Chen Y, Pinkenburg O, Camara B, Ollert M, Bindslev-Jensen C, Vasiliou V, Gorrini C, Lang PA, Lohoff M, Harris IS, Hiller K, Brenner D. Glutathione Primes T Cell Metabolism for Inflammation. Immunity. 2017 Apr 18;46(4):675-689. doi: 10.1016/j.immuni.2017.03.019.

2. Kalkavan H, Sharma P, Kasper S, Helfrich I, Pandyra AA, Gassa A, Virchow I, Flatz L, Brandenburg T, Namineni S, Heikenwalder M, Höchst B, Knolle PA, Wollmann G, von Laer D, Drexler I, Rathbun J, Cannon PM, Scheu S, Bauer J, Chauhan J, Häussinger D, Willimsky G, Löhning M, Schadendorf D, Brandau S, Schuler M, Lang PA*, Lang KS*. Spatiotemporally restricted arenavirus replication induces immune surveillance and type I interferon-dependent tumour regression. Nat Commun. 2017 Mar 1;8:14447. doi: 10.1038/ncomms14447. (* indicates shared authorship)

3. Crome SQ, Nguyen LT, Lopez-Verges S, Yang SY, Martin B, Yam JY, Johnson DJ, Nie J, Pniak M, Yen PH, Milea A, Sowamber R, Katz SR, Bernardini MQ, Clarke BA, Shaw PA, Lang PA, Berman HK, Pugh TJ, Lanier LL, Ohashi PS. A distinct innate lymphoid cell population regulates tumor-associated T cells. Nat Med. 2017 Mar;23(3):368-375. doi: 10.1038/nm.4278. Epub 2017 Feb 6.

4. Gil-Cruz C, Perez-Shibayama C, Onder L, Chai Q, Cupovic J, Cheng HW, Novkovic M, Lang PA, Geuking MB, McCoy KD, Abe S, Cui G, Ikuta K, Scandella E, Ludewig B. Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs. Nat Immunol. 2016 Dec;17(12):1388-1396. doi: 10.1038/ni.3566. Epub 2016 Oct 31.

5. Beyer M, Abdullah Z, Chemnitz JM, Maisel D, Sander J, Lehmann C, Thabet Y, Shinde PV, Schmidleithner L, Köhne M, Trebicka J, Schierwagen R, Hofmann A, Popov A, Lang KS, Oxenius A, Buch T, Kurts C, Heikenwalder M, Fätkenheuer G, Lang PA, Hartmann P, Knolle PA, Schultze JL. Tumor-necrosis factor impairs CD4(+) T cell-mediated immunological control in chronic viral infection. Nat Immunol. 2016 May;17(5):593-603. doi: 10.1038/ni.3399. Epub 2016 Mar 7.

6. Xu HC, Huang J, Khairnar V, Duhan V, Pandyra AA, Grusdat M, Shinde P, McIlwain DR, Maney SK, Gommerman J, Löhning M, Ohashi PS, Mak TW, Pieper K, Sic H, Speletas M, Eibel H, Ware CF, Tumanov AV, Kruglov AA, Nedospasov SA, Häussinger D, Recher M*, Lang KS*, Lang PA*. Deficiency of the B cell-activating factor receptor results in limited CD169+ macrophage function during viral infection. J Virol. 2015 May;89(9):4748-59. (* indicates shared authorship)

7. Shaabani N, Honke N, Dolff S, Görg B, Khairnar V, Merches K, Duhan V, Metzger S, Recher M, Barthuber C, Hardt C, Proksch P, Häussinger D, Witzke O, Lang PA*, Lang KS*. IFN-γ licenses CD11b+ cells to induce progression of systemic lupus erythematosus.J Autoimmun. 2015 Jun 19. pii: S0896-8411(15)00078-5. (* indicates shared authorship)

8. Qvartskhava N*, Lang PA*, Görg B, Pozdeev VI, Ortiz MP, Lang KS, Bidmon HJ, Lang E, Leibrock CB, Herebian D, Bode JG, Lang F, Häussinger D. Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase. Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5521-6. (* indicates shared authorship)

9. Itsumi M, Inoue S, Elia AJ, Murakami K, Sasaki M, Lind EF, Brenner D, Harris IS, Chio II, Afzal S, Cairns RA, Cescon DW, Elford AR, Ye J, Lang PA, Li WY, Wakeham A, Duncan GS, Haight J, You-Ten A, Snow B, Yamamoto K, Ohashi PS, Mak TW. Idh1 protects murine hepatocytes from endotoxin-induced oxidative stress by regulating the intracellular NADP+/NADPH ratio.Cell Death Differ. 2015 Apr 17.

10. Warsi J, Hosseinzadeh Z, Elvira B, Pelzl L, Shumilina E, Zhang DE, Lang KS, Lang PA, Lang F.  USP18 Sensitivity of Peptide Transporters PEPT1 and PEPT2. PLoS One. 2015 Jun 5;10(6):e0129365.

11. Khairnar V, Duhan V, Maney SK, Honke N, Shaabani N, Pandyra AA, Seifert M, Pozdeev V, Xu HC, Sharma P, Baldin F, Marquardsen F, Merches K, Lang E, Kirschning C, Westendorf AM, Häussinger D, Lang F, Dittmer U, Küppers R, Recher M, Hardt C, Scheffrahn I, Beauchemin N, Göthert JR, Singer BB, Lang PA, Lang KS. CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production. Nat Commun. 2015 Feb 18;6:6217.

12. Rahbar R, Lin A, Ghazarian M, Yau HL, Paramathas S, Lang PA, Schildknecht A, Elford AR, Garcia-Batres C, Martin B, Berman HK, Leong WL, McCready DR, Reedijk M, Done SJ, Miller N, Youngson B, Suh WK, Mak TW, Ohashi PS. B7-H4 expression by nonhematopoietic cells in the tumor microenvironment promotes antitumor immunity. Cancer Immunol Res. 2015 Feb;3(2):184-95.

13. McIlwain DR, Grusdat M, Pozdeev VI, Xu HC, Shinde P, Reardon C, Hao Z, Beyer M, Bergthaler A, Häussinger D, Nolan GP*, Lang KS*, Lang PA*. T-cell STAT3 is required for the maintenance of humoral immunity to LCMV. Eur J Immunol. 2015 Feb;45(2):418-27.

Lang E, Gatidis, Freise NF, Bock H, Kubitz R, Lauermann C, Orth HM, Klindt C, Schuier M, Keitel V, Reich M, Liu G, Schmidt S, Xu HC, Quadri SM, Herebian D, Pandyra AA, Mayatepek E, Gulbins E, Lang F, Häussinger D, Lang KS*, Föller M*, Lang PA*. Conjugated bilirubin triggers anemia by inducing erythrocyte death. Hepatology.2015 Jul 28. doi: 10.1002/hep.27338. (* indicates shared authorship)

14. Lang PA*, Meryk A*, Pandyra AA*, Brenner D, Brüstle A, Xu HC, Merches K, Lang F, Khairnar V, Sharma P, Funkner P, Recher M, Shaabani N, Duncan GS, Duhan V, Homey B, Ohashi PS, Häussinger D, Knolle PA, Honke N, Mak TW, Lang KS. Toso regulates differentiation and activation of inflammatory dendritic cells during virus infection. Cell Death Differ.2015 Jan; 22(1):164-73. doi: 10.1038/cdd.2014.138. (* indicates shared authorship)

15. Joedicke JJ, Myers L, Carmody AB, Messer RJ, Wajant H, Lang KS, Lang PA, Mak TW, Hasenkrug KJ, Dittmer U. Activated CD8+ T cells induce expansion of Vβ5+ regulatory T cells via TNFR2 signaling. J Immunol.2014 Sep 15;193(6):2952-60.

16. Parish IA, Marshall HD, Staron MM, Lang PA, Brüstle A, Chen JH, Cui W, Tsui YC, Perry C, Laidlaw BJ, Ohashi PS, Weaver CT, Kaech SM. Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1. J Clin Invest. 2014 Aug;124(8):3455-68.

17. Xu HC, Grusdat M, Pandyra AA, Polz R, Huang J, Sharma P, Deenen R, Köhrer K, Rahbar R, Diefenbach A, Gibbert K, Löhning M, Höcker L, Waibler Z, Häussinger D, Mak TW, Ohashi PS, Lang KS*, Lang PA*. Type I interferon protects antiviral CD8(+) T cells from NK cell cytotoxicity. Immunity. 2014 Jun 19;40(6):949-60. (* indicates shared authorship)

18. Grusdat M, McIlwain DR, Xu HC, Pozdeev VI, Knievel J, Crome SQ, Robert-Tissot C, Dress RJ, Pandyra AA, Speiser DE, Lang E, Maney SK, Elford AR, Hamilton SR, Scheu S, Pfeffer K, Bode J, Mittrücker HW, Lohoff M, Huber M, Häussinger D, Ohashi PS, Mak TW, Lang KS*, Lang PA*. IRF4 and BATF are critical for CD8+ T-cell function following infection with LCMV. Cell Death Differ. 2014 Feb 14. (* indicates shared authorship)

19. Brenner D, Brüstle A, Lin GH, Lang PA, Duncan GS, Knobbe-Thomsen CB, St Paul M, Reardon C, Tusche MW, Snow B, Hamilton SR, Pfefferle A, Gilani SO, Ohashi PS, Lang KS, Mak TW. Toso controls encephalitogenic immune responses by dendritic cells and regulatory T cells. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1060-5.

20. Holderried TA, Lang PA, Kim HJ, Cantor H. Genetic disruption of CD8+ Treg activity enhances the immune response to viral infection. Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21089-94.

21. Honke N, Shabaani N, Zhang DE, Iliakis G, Xu HC, Häussinger D, Recher M, Löhning M, Lang PA*, Lang KS*. Usp18 driven viral replication in dendritic cells contributes to break of immunological tolerance in autoimmune diabetes. PLoS Pathogens 2013 Oct; 9(10):e1003650. doi: 10.1371/journal.ppat.1003650. (* indicates shared authorship)

22. Garbers C, Kuck F, Aparicio-Siegmund S, Konzak K, Kessenbrock M, Sommerfeld A, Häussinger D, Lang PA, Brenner D, Mak TW, Rose-John S, Essmann F, Schulze-Osthoff K, Piekorz RP, Scheller J. Cellular senescence or EGFR signaling induces Interleukin 6 (IL-6) receptor expression controlled by mammalian target of rapamycin (mTOR).Cell Cycle. 2013 Nov 1;12(21):3421-32.

23. Raczkowski F, Ritter J, Heesch K, Schumacher V, Guralnik A, Höcker L, Raifer H, Klein M, Bopp T, Harb H, Kesper D, Pfefferle P, Grusdat M, Lang PA, Mittrücker HW, Huber M. The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells. Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15019-24.

24. Maretzky T, McIlwain DR, Issuree PD, Li X, Malapeira J, Amin S, Lang PA, Mak TW, Blobel CP. iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding.Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11433-8.

25. Lang PA*, Xu HC*, Grusdat M, McIlwain DR, Pandyra AA, Harris IS, Shaabani N, Honke N, Kumar Maney S, Lang E, Pozdeev VI, Recher M, Odermatt B, Brenner D, Häussinger D, Ohashi PS, Hengartner H, Zinkernagel RM, Mak TW, Lang KS. Reactive oxygen species delay control of lymphocytic choriomeningitis virus. Cell Death Differ.2013 Apr;20(4):649-58. (* indicates shared authorship)

26. Lang KS*, Lang PA*, Meryk A*, Pandyra AA*, Boucher LM, Pozdeev VI, Tusche M, Göthert JR, Haight J, Wakeham D, You-Ten A, McIlwain DR, Merchers K, Khairnar V, Recher M, Nolan GP, Hitoshi Y, Funkner P, Navarini AA, Verschoor A, Shaabani N, Honke N, Penn LZ, Ohashi PS, Häussinger D, Lee KH, Mak TW. Involvement of Toso in activation of monocytes, macrophages and granulocytes. Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2593-8. (* indicates shared authorship)

27. Isuree PDA, Maretzky T, McIlwain DR, Monette S, Qing X, Lang PA, Swendeman SL, Park-Min KH, Binder N, Kalliolias GD, Yarilina A, Horiuchi K, Ivashkiv LB, Mak TW, Salomon JE, Blobel CP. Novel role for IRHOM2 in the pathogenesis of inflammatory arthritis. J Clin Invest. 2013 Feb 1;123(2):928-32.

28. Lang PA*, Shaabani N*, Borkens S, Honke N, Scheu S, Booth S, Brenner D, Meryk A, Barthuber C, Recher M, Mak TW, Ohashi PS, Häussinger D, Griffiths GM, Thrasher AJ, Bouma G, Lang KS. Reduced type I interferon production by dendritic cells and weakened antiviral immunity in patients with Wiskott-Aldrich syndrome protein deficiency.J Allergy Clin Immunol.2013 Mar;131(3):815-24. (* indicates shared authorship)

29. Brüstle A*, Brenner D*, Knobbe CB, Lang PA, Virtanen C, Hershenfield BM, Reardon C, Lacher SM, Ruland J, Ohashi PS, Mak TW. The NF-κB regulator MALT1 determines the encephalitogenic potential of Th17 cells.J Clin Invest.2012 Dec 3;122(12):4698-709 (* indicates shared authorship)

30. Chen G, Dimitriou I, Milne L, Lang KS, Lang PA, Fine N, Ohashi PS, Kubes P, Rottapel R. The 3BP2 Adapter Protein Is Required for Chemoattractant-Mediated Neutrophil Activation.J Immunol. 2012 Sep 1;189(5):2138-50.

31. Kaesler S, Sobiesiak M, Kneilling M, Volz T, Kempf WE, Lang PA, Lang KS, Wieder T, Heller-Stilb B, Warskulat U, Häussinger D, Lang F, Biedermann T. Effective T-cell recall responses require the taurine transporter Taut.Eur J Immunol. 2012 Apr;42(4):831-41.

32. Shaabani N, Honke N, Lang PA, Görg B, Proksch P, Gailus N, Gotoh T, Häussinger D, Lang KS. Tunicamycin inhibits diabetes.Cell Physiol Biochem. 2012;29(3-4):595-602.

33. Recher M, Burns SO, de la Fuente MA, Volpi S, Dahlberg C, Walter JE, Moffitt K, Mathew D, Honke N, Lang PA, Patrizi L, Falet H, Keszei M, Mizui M, Csizmadia E, Candotti F, Nadeau K, Bouma G, Delmonte OM, Frugoni F, Fomin AB, Buchbinder D, Lundequist EM, Massaad MJ, Tsokos GC, Hartwig J, Manis J, Terhorst C, Geha RS, Snapper S, Lang KS, Malley R, Westerberg L, Thrasher AJ, Notarangelo LD. B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice.Blood. 2012 Mar 22;119(12):2819-28.

34. McIlwain DR*, Lang PA*, Maretzky T, Hamada K, Ohishi K, Maney SK, Berger T, Murthy A, Duncan G, Xu HC, Lang KS, Häussinger D, Wakeham A, Itie-Youten A, Khokha R, Ohashi PS, Blobel CP, Mak TW. iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS.Science. 2012 Jan 13;335(6065):229-32. (* indicates shared authorship)

35. Hao Z, Duncan GS, Su YW, Li WY, Silvester J, Hong C, You H, Brenner D, Gorrini C, Haight J, Wakeham A, You-Ten A, McCracken S, Elia A, Li Q, Detmar J, Jurisicova A, Hobeika E, Reth M, Sheng Y, Lang PA, Ohashi PS, Zhong Q, Wang X, Mak TW. The E3 ubiquitin ligase Mule acts through the ATM-p53 axis to maintain B lymphocyte homeostasis.J Exp Med. 2012 Jan 16;209(1):173-86.

36. Wang C, McPherson AJ, Jones RB, Kawamura KS, Lin GH, Lang PA, Ambagala T, Pellegrini M, Calzascia T, Aidarus N, Elford AR, Yue FY, Kremmer E, Kovacs CM, Benko E, Tremblay C, Routy JP, Bernard NF, Ostrowski MA, Ohashi PS, Watts TH. Loss of the signaling adaptor TRAF1 causes CD8+ T cell dysregulation during human and murine chronic infection.J Exp Med. 2012 Jan 16;209(1):77-91.

37. Lang PA*, Lang KS*, Xu HC, Grusdat M, Parish IA, Recher M, Elford AR, Dhanji S, Shaabani N, Tran CW, Dissanayake D, Rahbar R, Ghazarian M, Brüstle A, Fine J, Chen P, Weaver CT, Klose C, Diefenbach A, Häussinger D, Carlyle JR, Kaech SM, Mak TW, Ohashi PS. Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity.Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1210-5. (* indicates shared authorship)