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Startseite Institute Molekulare und Klinische Im... Forschung Arbeitsgruppen AG Simeoni

Arbeitsgruppe L. Simeoni

Research Interests

Lymphocyte signaling

Signaling via antigen receptors (i.e TCR and BCR) is crucial for the activation of lymphocytes and for the generation of an immune response. Defects in signal transduction may lead to pathological modifications such as chronic inflammation and cancer. Our group focuses on the analysis of how lymphocyte activation is regulated. We aim at better understanding the molecular mechanisms of immune responses in health and disease.

Currently, we focus on the following topics:

1. Analysis of post-translational modifications of Src-family kinases (SFKs):
SFKs such as Lck andFyn are crucial enzymes involved in the initiation of TCR-mediated signaling. Targeting of SFKs has recently become a novel therapeutic option to treat T-cell-mediated diseases. Regulation of SFKs activity occurs via phosphorylation of conserved tyrosine residues (e.g. Y394 and Y505 in Lck). In addition to these well-characterized sites, SFKs possess additional amino acid residues which can be modified post-translationally. However, their function remains still elusive. Thus, our aim is to further investigate the functional significance of post-translational modifications in the regulation of SFKs activation (Project B19 in SFB854).

2. Identification of new targets of oxidation in normal lymphocytes and leukemia cells.
Cysteine residues have recently become the focus of intensive investigation, as they function as “switches” upon oxidation of the thiol groups. Nevertheless, the function of thiol-switches in the regulation of lymphocyte biology is not completely understood. Our aim is to identify redox-sensitive signaling pathways in lymphocytes under both physiological and pathological conditions (Project TP-Simeoni in SPP1710). Additionally, we also aim at understanding the function of cysteine oxidation in acute myeloid leukemia (Project TP6 in Else Kröner-Forschungskolleg Magdeburg).

3. Regulation of T-cell activation by microRNAs.
MicroRNAs represent an abundant class of non-coding small RNAs that function as regulators of protein expression. Functional studies suggest that miRNAs regulate different aspects of the vertebrate immune system such as lineage commitment, proliferation, differentiation and migration and represent tempting therapeutic tools to modulate the immune response. To shed further light onto the role of miRNA in T-cell activation, we performed a miRNA array analysis. We have selected miRNAs candidates which are rapidly expressed upon T-cell stimulation. Our aim is to functionally characterize the selected miRNAs in T-cell activation (Project P12 in GRK1167).

Contact:

Simeoni, Prof. Dr. biol. hum. Luca

 

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