Research Topics and Financial Support

Post-transcriptional Gene Regulation in T Cells

Deregulation or inactivation of selected RNA-binding proteins induces the development of autoimmune and autoinflammatory diseases or boosts anti-tumor responses, respectively. We are trying to understand the complex interactions of selected RNA-binding proteins with newly identified cooperation partners and dissect how this network functions to control target mRNA expression via composite cis-elements. We aim to identify novel targets and markers and possible modes of therapeutic intervention. To reach this goal we undertake mechanistic analyses addressing the structural basis, function or regulation and employ global approaches to define binding sites and interactomes. We assess the physiologic importance of identified regulators in genetic models studying immune homeostasis, induced immune responses and pathologies.

Selected publications:

Tavernier, S. J. et al. A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation. Nat Commun 10, 5337, https://doi.org/10.1038/s41467-019-12704-6 (2019).

Essig, K. et al. Roquin targets mRNAs in a 3'-UTR-specific manner by different modes of regulation. Nat Commun 9, 3810, doi:10.1038/s41467-018-06184-3 (2018).

Jeltsch, K. M. et al. Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T(H)17 differentiation. Nat Immunol 15, 1079-1089, doi:10.1038/ni.3008 (2014).

Vogel, K. U. et al. Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation. Immunity 38, 655-668, doi:10.1016/j.immuni.2012.12.004 (2013).