應(yīng)用單細(xì)胞基因表達(dá)研究艾滋病疫苗在細(xì)胞水平上的反應(yīng)差異

 

Flatz博士表示在皮膚學(xué)研究中單細(xì)胞基因表達(dá)分析可以提供很多技術(shù)優(yōu)勢(shì)。

 

“在研究人類疾病時(shí)往往不能得到你所要的那么多的皮膚樣本，如果取走過(guò)多組織材料，病人會(huì)留下疤痕并會(huì)造成傷害。如果使用傳統(tǒng)的流式細(xì)胞法則需要大量的材料，而且大多時(shí)候只能檢測(cè)15-20個(gè)參數(shù)。使用Biomark技術(shù)你可以在每一個(gè)細(xì)胞中檢測(cè)多達(dá)96個(gè)參數(shù)，這就提供了很多機(jī)會(huì)來(lái)同時(shí)檢測(cè)多個(gè)基因轉(zhuǎn)錄因子、蛋白表達(dá)等。所以這種方法解決了樣品材料限制的問(wèn)題，使我們獲得很高的分辨率。我們希望找到和特異皮膚疾病如牛皮癬中有關(guān)的CD4和CD8細(xì)胞群，也可以預(yù)測(cè)應(yīng)用到紅斑狼瘡、濕疹或其他在皮膚病常見(jiàn)的免疫反應(yīng)疾病中。這可以幫助我們了解這些疾病，并可能把他們重新劃分成不同亞群，最終鑒定新的治療靶標(biāo)……我們可以從一個(gè)細(xì)胞中獲得比用以前的技術(shù)更多的信息�！�

 

Lukas Flatz博士在瑞士伯恩大學(xué)獲得醫(yī)學(xué)博士學(xué)位，一直從事免疫及皮膚學(xué)的臨床及科研工作。目前擔(dān)任瑞士洛桑醫(yī)院大學(xué)皮膚科的研究員和醫(yī)生，之前他擔(dān)任過(guò)伯恩大學(xué)傳染病研究所資深科學(xué)家。在美國(guó)國(guó)家衛(wèi)生研究院疫苗研究所病毒實(shí)驗(yàn)室、瑞士日內(nèi)瓦大學(xué)病理學(xué)及免疫學(xué)研究所、瑞士蘇黎世醫(yī)院大學(xué)實(shí)驗(yàn)免疫研究所等單位從事過(guò)博士后工作。

 

“使用Biomark技術(shù)你可以在每一個(gè)細(xì)胞中檢測(cè)多達(dá)96個(gè)參數(shù)……我們可以從一個(gè)細(xì)胞中獲得比用以前的技術(shù)更多的信息”-Flatz博士

 

Kerber R, T Rieger, C Busch., L Flatz, DD Pinschewer, BM Kümmerer, S Günther. 2011. Cross-species analysis of the replication complex of old world arenaviruses reveals two nucleoprotein sites involved in L protein function. J Virol. Dec; 85 (23): 12518-28.

Flatz L, R. Roychoudhuri, M. Honda, A. Filali-Mouhim, J-P. Goulet, N. Kettaf, M. Lin, M. Roederer, E.K Haddad, R.P. Sekaly, G.J. Nabel. 2011. Single cell gene-expression profiling reveals qualitatively distinct CD8 T cells elicited by different gene-based vaccines. Proc Natl Acad Sci U S A, Apr 5; 108 (14): 5724-9.

Bergthaler A.*, L. Flatz*, A.N. Hegazy, S. Johnson, E. Horvath, M. Löhning, D. Pinschewer. 2010. Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression. Proc Natl Acad Sci U S A, Dec 14;107(50):21641-6. *contributed equally

Pinschewer D.D., L.Flatz, R. Steinborn, E. Horvath, M. Fernandez, H.Lutz, M. Suter, A. Bergthaler. 2010. Innate and adaptive immune control of genetically engineered live-attenuated arenavirus vaccine prototypes. International Immunology, June 2010.

Flatz L., T. Rieger, D. Merkler, A. Bergthaler, T. Regen, M. Schedensack, L. Bestmann, A. Verschoor, M. Kreutzfeldt, W. Brück, U.-K. Hanisch, S. Günther, D.D. Pinschewer. 2010. T cell-dependence of Lassa fever pathogenesis. PLoS Pathogens, March 2010, Vol.6/3.

Flatz L., A.N. Hegazy, A. Bergthaler, A. Verschoor, C. Claus, M.Fernandez, L. Gattinoni, S. Johnson, F. Kreppel, S. Kochanek, M. van den Broek, A. Radbruch, F. Levy, P.H. Lambert, C.A. Siegrist, N.P. Restifo, M. Loehning, A. Ochsenbein, G.J. Nabel, D.D. Pinschewer. 2010. Development of replication-defective lymphocytic choriomeningitis virus vectors for induction of potent CD8+ T cell immunity. Nature Medicine, Feb. 17, 10.

Hegazy A.N, M. Peine, C. Helmstetter, I. Panse, A. Frohlich, A. Bergthaler , L. Flatz, D.D. Pinschewer, A. Radbruch, M. Loehning,. 2010. Interferons direct Th2 cell reprogramming to generate a stable GATA-3+T-bet+ cell subset with combined Th2 and Th1 cell functions. Immunity, Jan. 29, 10.

Bergthaler, A., L. Flatz, A. Verschoor, A.N. Hegazy, M. Holdener, K. Fink, B. Eschli, D. Merkler, R. Sommerstein, E. Horvath, M. Fernandez, A. Fitsche, B.M. Senn, J. Sjef Verbeek, B. Odermatt, C.-A. Siegrist, D.D. Pinschewer. 2009. Impaired antibody response causes persistence of prototypic T cell-contained virus. PLoS Biology, Apr 7;7(4).

Lang, P., L. Cervantes-Barragan, A. Verschoor, A.A. Navarini, M. Recher, M. Pellegrini, L. Flatz, A. Bergthaler, K. Honda, B. Ludewig, P.S. Ohashi, K.S. Lang. 2009. Hematopoietic cell-derived interferon controls viral replication and virus-induced disease. Blood 113:1045-52.

Heikenwalder, M., M. Prinz, N. Zeller, K. S. Lang, T. Junt, S. Rossi, A. Tumanov, H. Schmidt, J. Priller, L. Flatz, T. Rulicke, A. J. Macpherson, G. A. Hollander, S. A. Nedospasov, and A. Aguzzi. 2008. Overexpression of lymphotoxin in T cells induces fulminant thymic involution. Am J Pathol 172:1555-1570.