T Cell Signaling and Therapeutic Modulation Research Group
T cells are central regulators of adaptive immunity. They recognize antigens through the T cell receptor (TCR) and integrate signals from co-stimulatory, co-inhibitory, cytokine, and chemokine receptors to control their activation, differentiation, metabolism, and effector functions. Dysregulation of these signaling processes can lead to immunodeficiency, autoimmunity, chronic inflammation, and cancer.
Our research aims to understand the molecular mechanisms that regulate T-cell signaling and to use this knowledge to develop new strategies for therapeutic modulation of immune-cell function. We combine biochemical and cellular approaches with quantitative signaling analyses, proteomics, interactome and transcriptomic studies, pharmacological perturbation, functional analyses, and computational approaches including network analysis and artificial intelligence in collaboration with the group of Prof. Ernesto W. De Luca https://www.hcai.ovgu.de/.
- Molecular regulation of T-cell signaling
A major focus of our work is to understand how signals are initiated and propagated through the T-cell receptor signaling machinery. We are particularly interested in the regulation of ZAP-70, its molecular interactions, and the mechanisms that connect receptor-proximal signaling to downstream T-cell activation.
In parallel, we investigate the functional organization of T-cell signaling networks, with particular interest in pathway dependencies, cross-talk, feedback mechanisms, and other regulatory interactions that shape T-cell responses.
- Signaling and engineering of therapeutic immune cells
Engineered immune receptors, including chimeric antigen receptors (CARs), use components of physiological lymphocyte signaling but can differ substantially in signal strength, dynamics, activation threshold, and spatial organization.
We investigate how proximal signaling networks determine the activation and functionality of engineered immune cells and how these networks can be rationally modified to improve cellular responses. A particular interest is the dynamic organization of receptor-associated signaling networks and the identification of signaling features associated with immune-cell function.
Our goal is to translate mechanistic insights into the rational design and improvement of engineered cellular therapies.
- Therapeutic modulation of T-cell responses
We investigate how T-cell signaling and function can be therapeutically modulated. A particular focus lies on glucocorticoids and immunomodulatory compounds, including natural products and their derivatives, that either enhance or suppress T-cell responses.
We aim to understand their molecular mechanisms of action and how modulation of specific signaling pathways translates into altered T-cell activation and function. These studies may provide new strategies for controlling immune responses in immune-mediated diseases and cellular immunotherapy.