Klinik für Hautkrankheiten

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Forschungsgruppe

Research fields

We are investigating the molecular and cellular regulation of T cell responses and aim to use this knowledge to understand and improve immunotherapies

Current research topics

Cyclic adenosine monophosphate (cAMP) serves cells of all life forms as a signaling messenger and to regulate gene expression. Regulatory T cells (Treg) transfer cAMP to other immune cells to suppress their function (J. Exp. Med 2007). In melanomas, melanoma cells acidify their environment by lactate, which instigates cAMP production in monocytes, suppressing their anti-tumor activities (Nat. Immunol. 2018).

We have collaborated with colleagues in chemistry and immunology to develop nanoparticulate micelles that release an cAMP (Adenylate cyclase) inhibitor in tumor tissue.  Local application of such inhibitor-loaded particles suppresses melanoma growth through metabolic reprogramming of infiltrating immune cells. We are currently further improving the cAMP inhibitor particles to make them systemically and thus clinically applicable. At the same time, we continue to investigate the molecular basis of cAMP-mediated reprogramming of the immune system to identify alternative, cell-specific intervention points.

Regulatory T cells (Treg) have -in addition to their role in suppressing immune responses- an important and non-redundant role in tissue repair. The cellular and molecular mechanisms underlying the development and function of 'repair Treg' in injured tissue are poorly defined.

We recently identified a specialized population of Treg that develops in venous blood clots and controls clot resolution by potentiating monocyte recruitment, differentiation and matrix metalloproteinase (MMP) activity through the matricellular protein, secreted protein acidic and rich in cysteine (SPARC) (Shahneh et al., 2020). We believe that 'clot Treg‘ and their products offer new therapeutic opportunities for the treatment of sterile tissue inflammation, such as in vascular diseases and tumors.

 

Chronic venous insufficiency (CVI) is a very common health problem. The most common manifestations of chronic venous disease are dilated skin veins and varicose veins. The exact etiology of CVI remains unclear, but inflammatory processes are thought to be of critical importance. Varicose veins have a larger infiltrate of inflammatory cells than normal veins, and monocytes are a major component.

Varicose veins removed during surgery to correct venous dysfunction or for cosmetic reasons and their healthy counterpart used in cardiac bypass surgery provide an exceptional opportunity to understand the activities of human vascular monocytes.

We are exploring the specific function of monocytes in inflamed venous tissue and expect to contribute to the understanding of CVI pathology and, moreover, chronic tissue inflammation.

Publications

Inflammatory Monocyte Counts Determine Venous Blood Clot Formation and Resolution.

Shahneh F, Christian Probst H, Wiesmann SC, A-Gonzalez N, Ruf W, Steinbrink K, Raker VK, Becker C.
Arterioscler Thromb Vasc Biol. 2021 Dec 16:ATVBAHA121317176. doi: 10.1161/ATVBAHA.121.317176.

Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression.

Johann K, Bohn T, Shahneh F, Luther N, Birke A, Jaurich H, Helm M, Klein M, Raker VK, Bopp T, Barz M, Becker C.
Nat Commun. 2021 Oct 13;12(1):5981. doi: 10.1038/s41467-021-26269-w.

Specialized regulatory T cells control venous blood clot resolution through SPARC.
Shahneh F, Grill A, Klein M, Frauhammer F, Bopp T, Schäfer K, Raker V, Becker C.
Blood. 2020 Sep 15:blood.2020005407. doi: 10.1182/blood.202000540
 
Thrombo-Inflammation in Cardiovascular Disease: An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis.
d'Alessandro E, Becker C, Bergmeier W, Bode C, Bourne JH, Brown H, Buller HR, Ten Cate-Hoek AJ, Ten Cate V, van Cauteren YJM, Cheung YFH, Cleuren A, Coenen D, Crijns HJGM, de Simone I, Dolleman SC, Klein CE, Fernandez DI, Granneman L, van T Hof A, Henke P, Henskens YMC, Huang J, Jennings LK, Jooss N, Karel M, van den Kerkhof D, Klok FA, Kremers B, Lämmle B, Leader A, Lundstrom A, Mackman N, Mannucci PM, Maqsood Z, van der Meijden PEJ, van Moorsel M, Moran LA, Morser J, van Mourik M, Navarro S, Neagoe RAI, Olie RH, van Paridon P, Posma J, Provenzale I, Reitsma PH, Scaf B, Schurgers L, Seelig J, Siegbahn A, Siegerink B, Soehnlein O, Soriano EM, Sowa MA, Spronk HMH, Storey RF, Tantiwong C, Veninga A, Wang X, Watson SP, Weitz J, Zeerleder SS, Ten Cate H; Scientific Reviewer Committee.
Thromb Haemost. 2020 Apr;120(4):538-564. doi: 10.1055/s-0040-1708035.

Acute deep vein thrombosis suppresses peripheral T cell effector function.
Prochaska JH, Luther N, Brähler M, Schulz A, Hermanns MI, Lackner KJ, Espinola-Klein C, Münzel T, Wild PS, Becker C.
Br J Haematol. 2019 Mar;184(5):847-850. doi: 10.1111/bjh.15192.

Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages.
Bohn T, Rapp S, Luther N, Klein M, Bruehl TJ, Kojima N, Aranda Lopez P, Hahlbrock J, Muth S, Endo S, Pektor S, Brand A, Renner K, Popp V, Gerlach K, Vogel D, Lueckel C, Arnold-Schild D, Pouyssegur J, Kreutz M, Huber M, Koenig J, Weigmann B, Probst HC, von Stebut E, Becker C, Schild H, Schmitt E, Bopp T.
Nat Immunol. 2018 Dec;19(12):1319-1329. doi: 10.1038/s41590-018-0226-8. 

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. doi: 10.1161/CIRCRESAHA.116.309301.

 
 
 
 

Team

Laboratory Head
PD Dr. rer. nat. Christian Becker
T 0251 83-52453
christiangeorg.becker@ukmuenster.de

Pubmed: F-5384-2010
ORCID: orcid.org/0000-0002-1716-7208

Staff:
Friederike Pauline Neesen
Doğa Uncuer, PostDoc

Join us

The lab recently relocated from Mainz to Münster. I am looking for talented scientists and students. If you are interested in joining my group or need further information please do not hesitate to contact me.