We investigate how translational control shapes immune cell function and how defects in the protein synthesis machinery cause human disease. Our work combines biochemistry, genomics, and human genetics to understand translation at the molecular, cellular, and organismal level.
Protein synthesis is a fundamental cellular process, yet its regulation is remarkably context-dependent. Immune cells face unique translational challenges: they must rapidly reprogram their proteomes upon activation, sustain intense biosynthetic activity during clonal expansion, and fine-tune effector molecule production. We seek to understand how translational control mechanisms orchestrate these processes—and what goes wrong in disease.
T lymphocytes undergo dramatic changes upon antigen recognition: within hours, a quiescent cell transforms into a biosynthetic powerhouse. This process requires coordinated reprogramming of mRNA translation, yet the mechanisms remain poorly understood.
We use ribosome profiling, selective 40S footprinting, and CRISPR screens to dissect translational control in primary human T cells.
T Vatovec, AL Neehus, KJL Jackson, J Bohlen
Nature Immunology
Demonstrates that somatic CBL deficiency selectively impairs B cell development while sparing T cell function, revealing cell-type specific requirements for this E3 ubiquitin ligase.
J Bohlen, I Bagaric, T Vatovec, M Ogishi, JL Casanova, J Bustamante
Journal of Clinical Investigation
Reveals the molecular mechanism underlying autoinflammation in CBL-deficient patients, identifying constitutive ERK activation in monocytes as the driver of disease.
Ribosomopathies—diseases caused by mutations in ribosomal proteins or assembly factors—often manifest with selective tissue defects despite ribosomes being required in every cell. Intriguingly, immunodeficiency is a common feature of several ribosomopathies, suggesting immune cells are particularly vulnerable to translational stress.
We study patient-derived cells and mouse models carrying ribosomopathy-associated mutations, combining proteomics, ribosome profiling, and functional assays.
J Bohlen, Q Zhou, Q Philippot, J Bustamante, Q Zhang, JL Casanova
Cell
Landmark discovery showing that MCTS1 is required for JAK2 translation in human immune cells, explaining why MCTS1-deficient patients are susceptible to mycobacterial infections.
J Bohlen, L Harbrecht, S Blanco, KC von Hohenberg, K Fenzl, G Kramer, B Bukau, AA Teleman
Nature Communications
Establishes that DENR facilitates ribosome recycling after uORF translation, enabling reinitiation at main ORFs including the stress-response transcription factor ATF4.
Transfer RNAs are essential adaptors in protein synthesis, yet mutations affecting tRNA biogenesis and modification cause a surprising spectrum of human diseases—including autoinflammatory syndromes. We investigate how defects in tRNA metabolism trigger inappropriate immune activation.
We combine tRNA sequencing, codon-resolution ribosome profiling, and genetic perturbation to understand how tRNA metabolism shapes the immune cell proteome.
We develop and apply cutting-edge methods to study translation with unprecedented resolution.
Genome-wide snapshots of translation
Tracking scanning ribosomes
Functional genomics in primary cells
Human disease in the dish
