Visual Universitätsmedizin Mainz

Research Team PD Dr. Christian Becker

PD Dr. rer. nat. Becker
PD Dr. rer. nat. Christian Becker

Tel. 06131-17-2917
06131-17-8277
Fax 06131-17-474523
christian.becker@unimedizin-mainz.de

Staff:

Natascha Anna Maria Luther, PhD Student

Fatemeh Shahneh, PhD Student

Ana Flávia Fernandes Ribas Nardy, PhD sudent (guest)

Marie Helen-Winter, MD Student

We are constantly looking for talented scientist und students. If you are interested in joining our Group or Need further Information please do not hesitate to contact us.

Contact:

Lab 147: 06131 17-8147

Office: 06131 17-2917

 

Research fields:

  • molecular characterization of T cell function
  • Development of T cell modulating agents

Selected Publications:

Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.
Luther N, Shahneh F, Brähler M, Krebs F, Jäckel S, Subramaniam S, Stanger C, Schönfelder T, Kleis-Fischer B, Reinhardt C, Probst HC, Wenzel P, Schäfer K, Becker C.

Circ Res. 2016 Dec 9;119(12):1286-1295.

Interferon-α Suppresses cAMP to Disarm Human Regulatory T Cells. 
Bacher N, Raker V, Hofmann C, Graulich E, Schwenk M, Baumgrass R, Bopp T, Zechner U, Merten L, Becker C*, Steinbrink K*.
Cancer Res. 2013 Sep 15;73(18):5647-56. doi: 10.1158/0008-5472.CAN-12-3788. Epub 2013 Jul 22. *shared senior authors

Angiotensin II-Induced Vascular Dysfunction Depends on Interferon-γ-Driven Immune Cell Recruitment and Mutual Activation of Monocytes and NK-Cells.
Kossmann S, Schwenk M, Hausding M, Karbach SH, Schmidgen MI, Brandt M, Knorr M, Hu H, Kröller-Schön S, Schönfelder T, Grabbe S, Oelze M, Daiber A, Münzel T, Becker C*, Wenzel P*.
Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1313-9. doi: 10.1161/ATVBAHA.113.301437 *shared senior authors

Repression of cyclic adenosine monophosphate upregulation disarms and expands human regulatory T cells.
Klein M, Vaeth M, Scheel T, Grabbe S, Baumgrass R, Berberich-Siebelt F, Bopp T, Schmitt E, Becker C.
J Immunol. 2012 Feb 1;188(3):1091-1097

CD4-mediated regulatory T-cell activation inhibits the development of disease in a humanized mouse model of allergic airway disease.

Martin H, Reuter S, Dehzad N, Heinz A, Bellinghausen I, Saloga J, Haasler I, Korn S, Jonuleit H, Buhl R, Becker C*, Taube C*.

J Allergy Clin Immunol. 2012 Feb;129(2):521-528 *shared senior authors

Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells.

Becker C, Taube C, Bopp T, Becker C, Michel K, Kubach J, Reuter S, Dehzad N, Neurath MF, Reifenberg K, Schneider FJ, Schmitt E, Jonuleit H.

Blood. 2009 Aug 6;114(6):1263-9.

Adoptive tumor therapy with T lymphocytes enriched through an IFN-gamma capture assay.

Becker C, Pohla H, Frankenberger B, Schüler T, Assenmacher M, Schendel DJ, Blankenstein T.

Nat Med. 2001 Oct;7(10):1159-62

Funding:

Bundesministerium für Bildung und Forschung, NMFZ, Deutsche Forschungsgemeinschaft

Projects:

 

B8   Development and testing of nanoparticles repealing cAMP-mediated immunosuppression in melanoma

Tumor-mediated immunosuppression represents an important obstacle in the development of efficient immunotherapeutic regimen. Major mechanisms of immunosuppression consist in production of immunosuppressive molecules by the tumor and in the activation of regulatory T cells (Treg).

The second messenger cyclic adenosine monophosphate (cAMP) is a versatile controller of innate inflammatory activity, an important component in Treg suppressive function and controls growth and metastasis in melanoma cells. Its pathway thus represents an attractive target for immunotherapeutic intervention with melanoma growth. Due to a broad physiological importance, however, the cAMP pathway should not be addressed on the systemic level. The project therefore aims to develop nanoparticles as controlled release carrier for interference with melanoma-mediated immunosuppression by site-specific inhibition of cAMP Formation.

 

 

Role of T helper cell activation and effector pathways in the pathogenesis and progression of vascular Inflammation

Established therapies in cardiovascular disease are mainly restricted to alleviating symptoms and preventing aggravation. Exploration of the pathogenic interface, particularly the immune cell response, will allow new therapeutic strategies based on established immune therapeutic drugs and regimen. T lymphocytes are important participants in inflammatory responses both through their adaptive and innate functions. Recent evidence indicates that functionally distinct T helper cell subsets, distinguishable by their patterns of cytokine production, contribute to vascular inflammation in the setting of artheriosclerosis, hypertension and autoimmune vasculitis and also participate in venous thrombosis. However, the molecular events regulating perivascular T cell recruitment and inflammatory activity are largely unknown. This project aims at the identification of murine T cell subsets and their activation and effector pathways that contribute to vascular inflammation in the setting of thrombosis and angiotensin II-induced hypertension. Ultimately, the project intends to characterize changes in T cell composition and function in the blood of patients with thromboembolic disease and evaluate patient T cell reactivities in a humanized mouse model.

Regulatory T cells in postthrombotic vessel repair

Postthrombotic syndrome (PTS) is a chronic and frequent complication in deep vein thrombosis (DVT) attributed to insufficient thrombus resolution and persistent vein wall inflammation not addressed by current anticoagulant therapy. Identifying new strategies to dampen DVT-associated vein wall inflammation and improve vessel repair could therefore be beneficial for PTS prevention.

Regulatory T cells (Treg) suppress numerous immune activities and have been recently rediscovered as important regulators of non-immunological processes. We observed an accumulation of Treg in the vein wall after DVT induction in the inferior vena cava (IVC) ligation model, suggesting a role of these cells in regulation of vein wall inflammation and/or vessel repair. To address the potential therapeutic effects of modulating this population and identify the vascular regulating factors it produces, we seek to selectively deplete and activate Treg after DVT induction and perform gene expression profiling of Treg accumulating in the inflamed vein wall. Identified Treg factors will be functionally characterized in respect of their impact on postthrombotic vein wall inflammation/repair in vivo and on vascular cells in vitro.