T cell Signaling group
T Cell Signal Transduction 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 translate this knowledge into new strategies for immunotherapy and pharmacological immune modulation. We combine molecular and cellular approaches with quantitative proteomics, transcriptomics, imaging, and functional analyses of primary human T cells and engineered cellular models.
Our work focuses on three interconnected research areas:
• Molecular regulation of TCR signaling
The protein tyrosine kinases LCK and ZAP-70 initiate and propagate signaling downstream of the TCR. We investigate how their activity, localization, molecular interactions, and conformational dynamics are regulated and how alterations in these processes affect T-cell activation. A particular focus lies on the functional characterization of disease-associated mutations and previously unrecognized regulatory regions in signaling proteins.
• Signaling in engineered T cells
Engineered immune receptors, including chimeric antigen receptors (CARs), use components of physiological T-cell signaling but can differ substantially in signal strength, dynamics, and spatial organization. We investigate how proximal signaling networks determine the activation, functionality, and persistence of engineered T cells. By integrating experimental data with computational analyses and artificial intelligence, we aim to identify signaling features that predict T-cell functionality and guide the rational optimization of engineered immune receptors. Our long-term goal is to translate this mechanistic knowledge into safer and more effective cellular immunotherapies.
• Identification and characterization of immunomodulatory compounds
Natural products and their derivatives represent an important source of novel therapeutic agents. We identify compounds that either enhance or suppress human T-cell responses and characterize their molecular mechanisms of action. By integrating functional assays with signaling and transcriptomic analyses, we aim to discover new pharmacological tools and potential lead compounds for treating immune-related diseases.