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Polansky-Biskup lab

How the structure of the genome shapes the immune system in health and disease

Introduction
Members
Cooperation partners
Selected Publications

Immuno-Epigenetics

Not only the DNA sequence – our genome – but also the 3D structure of our genome – the ‘epi-genome’ – is essential in determining the type and function of a cell. That’s why the analysis of the epigenome facilitates deep insights into the developmental history of a cell and its current gene expression profile, but also allows deductions on its future destiny.

CD4+ T lymphocytes provide immunological protection by differentiation into various functional subtypes which efficiently clear invading pathogens, prevent tumor formation and maintain immunological memory towards re-occurring pathogens. However, they are also one of the main contributors to chronic inflammation and auto-immunity during disease.

Therefore, our group focuses on the analysis and interpretation of epigenomic structures of CD4+ T lymphocytes during health and during chronic inflammatory diseases such as rheumatoid arthritis. These insights will not only highlight promising candidate genes which are involved in the disease-associated mis-differentiation of pro-inflammatory T cells, but will also pinpoint promising target elements for therapeutic intervention, as epigenetic modifications are in general reversible and hence, ‘druggable’.

We employ state-of-the-art epigenome-profiling techniques to characterize the epigenome of T lymphocytes during health and disease. From the epigenomic data, we can learn about their differentiation and activation state, find disease-associated biomarkers and identify target genes which contribute to their pathogenic function during disease.

As the second step, we aim at understanding how these epigenetic changes functionally contribute to disease-associated differentiation and senescence of T lymphocytes. We have shown in the past how epigenetic control elements mediate permanent imprinting of a cellular function during normal T cell differentiation. This knowledge will now be applied to clarify disease-associated gene-expression. In addition, we found that the degree of cellular senescence is also encoded in the epigenome and now analyze the molecular mechanisms involved in this process, as cellular senescence has been reported to increase during chronic inflammation.

Our third line of research concentrates on elucidating how targeted manipulation of the epigenetic machinery can influence the function and survival of a cell as a potential therapeutic approach. For this, we employ state-of-the-art ‘epigenetic editing’ techniques including the CRISPR/Cas9-tools, to specifically change the epigenetic state of regulatory elements of disease-associated genes. With this, we want to re-program pathogenic T cells into their normal counterparts or to equip T cell populations with a favorable function for their application in adoptive T cell therapy against auto-immune diseases. Furthermore, the targeted manipulation of the epigenetic senescence mechanism might prevent the accumulation of senescent T cells during chronic inflammation and improve the survival of highly expanded T cell populations during adoptive T cell therapy.

Group Leader
    Dr. Julia Polansky-Biskup

Dr. Julia Polansky-Biskup

Deutsches Rheuma-Forschungszentrum Berlin
Immuno-Epigenetics
Charitéplatz 1
10117 Berlin

Tel: +49 3028460729
Tel: +49 30450524197
Fax: +49 3028460656
julia.polansky@drfz.de

Keywords
Epigenetics
Epigenetic editing
Immune-regulation
T-Lymphocytes
Cellular senescene

Liaison-Gruppe
Continue to Members

Group leader:
Dr. Julia K. Polansky-Biskup

PhD students:
Christopher Kressler

Master students:
Wojciech Leszczynski
Lydia Verlaat
Dania Hamo
Marcus Fricke

Group Leader
    Dr. Julia Polansky-Biskup

Dr. Julia Polansky-Biskup

Deutsches Rheuma-Forschungszentrum Berlin
Immuno-Epigenetics
Charitéplatz 1
10117 Berlin

Tel: +49 3028460729
Tel: +49 30450524197
Fax: +49 3028460656
julia.polansky@drfz.de

Keywords
Epigenetics
Epigenetic editing
Immune-regulation
T-Lymphocytes
Cellular senescene

Liaison-Gruppe
Continue to Cooperation partners

Benedikt Brors, Jürgen Eils (beide DKFZ Heidelberg)

Ho-Ryun Chung (MPI-MG Berlin)

Thomas Hildebrandt, Susanne Holtze (IZW, Berlin)

Jochen Hühn (HZI Braunschweig)

Thomas Lengauer (MPI-INF Saarbrücken)

Thomas Manke (MPI-IE Freiburg)

Nikolaus Rajewsky, Wei Chen (beide MDC Berlin)

Philip Rosenstiel (Uni Kiel)

Jürgen Ruland (TU München)

Birgit Sawitzki (Charite Berlin)

Alexander Scheffold (Charite, Berlin)

Joachim L. Schultze (Uni Bonn)

Marcel Schulz (Uni Saabrücken)

Uta Syrbe (Charite Berlin)

Hans-Dieter Volk (Charite und BCRT Berlin)

Group Leader
    Dr. Julia Polansky-Biskup

Dr. Julia Polansky-Biskup

Deutsches Rheuma-Forschungszentrum Berlin
Immuno-Epigenetics
Charitéplatz 1
10117 Berlin

Tel: +49 3028460729
Tel: +49 30450524197
Fax: +49 3028460656
julia.polansky@drfz.de

Keywords
Epigenetics
Epigenetic editing
Immune-regulation
T-Lymphocytes
Cellular senescene

Liaison-Gruppe
Continue to Selected Publications

Szilagyi BA, Triebus J, Kressler C, de Almeida M, Tierling S, Durek P, Mardahl M, Menning A, Engelbert D, Floess S, Huehn J, Syrbe U, Walter J, Polansky JK*, Hamann A* (2017). Gut memories don´t fade: Expression of the gut homing receptor integrin α4β7 is stably imprinted in CD4+ memory T cells by epigenetic modification of regulatory regions in the itga4 locus. * shared last authorship. Mucosal Immunology, doi: 10.1038/mi.2017.7.

Schmidt F, Gasparoni N, Gasparoni G, Gianmoena K, Cadenas C, Polansky JK, Ebert P, Nordström K, Barann M, Sinha A, Fröhler S, Xiong J, Amirabad A, Ardakani F, Hutter B, Zipprich G, Felder B, Eils J, Brors B, Chen W, Hengstler J, Hamann A, Lengauer T, Rosenstiel P, Walter J, Schulz MH (2017). Combining transcription factor binding affinities with open chromatin data for accurate gene expression prediction. Nuclear Acid Res, 9;45(1):54-66.

Stunnenberg HG, Hirst M, Abrignani S, […] Polansky J, […] Zipprich G (2016). The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery. Cell. 17;167(5):1145-1149.

Durek P, Nordström K, Gasparoni G, Kressler C, de Almeida M, Salhab A, Bassler K, Ulas T, Xiong J, Glažar P, Klironomos F, Sinha A, Kinkley S, Yang X, Schmidt F, Dehghani Amirabad A, Behjati Ardakani F, Feuerbach L, Gorka O, Ebert P, Müller F, Li N, Frischbutter S, Schlickeiser S, Cendon C, Fröhler S, Felder B, Gasparoni N, Imbusch CD, Hutter B, Zipprich G, Tauchmann Y, Reinke S, Wassilew G, Hoffmann U, Arrigoni L, Richter AS, Sieverling L, Chang H-D, Syrbe U, Manke T, Kalus U, Eils J, Brors B, Ruland J, Lengauer T, Rajewsky N, Chen W, Schulz MH, Dong J, Sawitzki B, Chung H-R, Rosenstiel P, Schultze JL, Radbruch A, Walter J, Hamann A, Polansky JK. (2016) Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development. Immunity, 45, 1148-1161.

Pink M, Ratsch BA, Mardahl M, Durek P, Polansky JK, Karl M, Baumgrass R, Wallner S, Cadenas C, Gianmoena K, Floess S, Chen W, Nordstroem K, Tierling S, Olek S, Walter J, Hamann A, Syrbe U: (2016) Imprinting of Skin/Inflammation Homing in CD4+ T Cells Is Controlled by DNA Methylation within the Fucosyltransferase 7 Gene. J Immunol, doi:10.4049/jimmunol.1502434

Kinkley S, Helmuth J, Polansky JK, Dunkel I, Gasparoni G, Fröhler S, The DEEP consortium, Chen W, Walter J, Hamann A, Chung H-R. (2016) reChIP-seq reveals widespread bivalency of H3K4me3 and H3K27me3 in CD4+ memory T-Cells. Nature Communications, vol. 7, pp. 12514.

Goldstein JD, Burlion A, Zaragoza B, Sendeyo K, Polansky JK, Huehn J, Piaggio E, Salomon BL, Marodon G. (2016) Inhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression. PLoS One. Apr 14;11(4):e0153682.

Polansky JK, Bahri R, Divivier M, Duitman EH, Vock C, Goyeneche-Patino DA, Orinska Z, Bulfone-Paus S. (2016) High dose CD11c-driven IL15 is sufficient to drive NK cell maturation and anti-tumor activity in a trans-presentation independent manner. Scientific Reports Jan 29;6:19699.

Bahri R, Pateras IS, D’Orlando O, Goyeneche-Patino DA, Campbell M, Polansky JK, Sandig H, Papaioannou M, Evangelou K, Foukas PG, Gorgoulis VG, Bulfone-Paus S. (2015) IL-15 suppresses colitis-associated colon carcinogenesis by inducing antitumor immunity. Oncoimmunology. 4(9):e1002721.

Polansky JK, Syrbe U, Hamann A. (2013) Epigenetic analyses – new therapeutic approaches for rheumatic diseases? Z Rheumatol. 72(8):804-8.

Toker A, Engelbert D, Garg G, Polansky JK, Floess S, Miyao T, Baron U, Düber S, Geffers R, Giehr P, Schallenberg S, Kretschmer K, Olek S, Walter J, Weiss S, Hori S, Hamann A, Huehn J. (2013) Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus. J Immunol. 190(7):3180-8.

Polansky JK, Schreiber L, Thelemann C, Ludwig L, Krüger M, Baumgrass R, Cording S, Floess S, Hamann A and Huehn J (2010). Methylation matters: Binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells. J Mol Med. Oct;88(10):1029-40.

Polansky JK, Floess S, Freyer J, Hamann A and Huehn J. (2009). Epigenetic regulation of Foxp3 expression in regulatory T cells. Book chapter in The Epigenetics of Autoimmune disease, John Wiley & Sons, Inc.

Huehn J, Polansky JK, Hamann A. (2009). Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat Rev Immunol. Feb;9(2):83-9.

Polansky JK, Kretschmer K, Freyer J, Floess S, Garbe A, Baron U, Olek S, Hamann A, von Boehmer H, Huehn J (2008). DNA methylation controls Foxp3 gene expression. Eur J Immunol. 38(6):1654-63.

Apostolou I, Verginis P, Kretschmer K, Polansky J, Huehn J, von Boehmer H. (2008). Peripherally Induced Treg: Mode, Stability, and Role in Specific Tolerance. J Clin Immunol. Nov;28(6):619-24.

Polansky JK and Huehn J (2007). To be or not to be a Treg: Epigenetic regulation of Foxp3 expression in regulatory T cells. Z Rheumatol. 66(5): 417-20.

Floess S, Freyer J, Siewert C, Baron U, Olek S, Polansky J, Schlawe K2 Chang HD, Bopp T, Schmitt E, Klein-Hessling S, Serfling E, Hamann A, and Huehn J (2007). Epigenetic control of the foxp3 locus in regulatory T cells. PLoS biology 5: e38.

Marson A, Kretschmer K, Frampton GM, Jacobsen ES, Polansky JK, MacIsaac KD, Levine SS, Fraenkel E, von Boehmer H, Young RA (2007). Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature 22; 445(7130):931-5.

Group Leader
    Dr. Julia Polansky-Biskup

Dr. Julia Polansky-Biskup

Deutsches Rheuma-Forschungszentrum Berlin
Immuno-Epigenetics
Charitéplatz 1
10117 Berlin

Tel: +49 3028460729
Tel: +49 30450524197
Fax: +49 3028460656
julia.polansky@drfz.de

Keywords
Epigenetics
Epigenetic editing
Immune-regulation
T-Lymphocytes
Cellular senescene

Liaison-Gruppe
Continue to Introduction