Celluloepidemiology-A paradigm for quantifying infectious disease dynamics on a population level.

To complement serology as a tool in public health interventions, we introduced the "celluloepidemiology" paradigm where we leveraged pathogen-specific T cell responses at a population level to advance our epidemiological understanding of infectious diseases, using SARS-CoV-2 as a model. Applying flow cytometry and machine learning on data from more than 500 individuals, we showed that the number of T cells with positive expression of functional markers not only could distinguish patients who recovered from COVID-19 from controls and pre-COVID donors but also identify previously unrecognized asymptomatic patients from mild, moderate, and severe recovered patients. The celluloepidemiology approach was uniquely capable to differentiate health care worker groups with different SARS-CoV-2 exposures from each other.

An NGS-based approach for precise and footprint-free CRISPR-based gene editing in human stem cells.

Precise gene editing with conventional CRISPR/Cas9 is often constrained by low knock-in (KI) efficiencies (≈ 2-20 %) in human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). This limitation typically necessitates labour-intensive manual isolation and genotyping of hundreds of colonies to identify correctly edited cells. Fluorescence- or antibiotic-based enrichment methods facilitate the identification process but can compromise cell viability and genomic integrity.

Analysis of Wilms' tumor protein 1 specific TCR repertoire in AML patients uncovers higher diversity in patients in remission than in relapsed.

The Wilms' tumor protein 1 (WT1) is a well-known and prioritized tumor-associated antigen expressed in numerous solid and blood tumors. Its abundance and immunogenicity have led to the development of different WT1-specific immune therapies. The driving player in these therapies, the WT1-specific T-cell receptor (TCR) repertoire, has received much less attention.

Generation of four distinct isogenic cell lines with truncating variants in I-band or A-band titin.

Truncating variants in TTN (TTNtv) are present in 15-25 % of patients with idiopathic dilated cardiomyopathy. Interestingly, the pathogenicity of TTNtv seems to be linked to their location within the gene. More proximal I-band TTNtv (TTNtvI) harbour less pathogenic potential than distant A-band TTNtv (TTNtvA).

Investigation of Strategies to Block Downstream Effectors of AT1R-Mediated Signalling to Prevent Aneurysm Formation in Marfan Syndrome.

Cardiovascular outcome in Marfan syndrome (MFS) patients most prominently depends on aortic aneurysm progression with subsequent aortic dissection. Angiotensin II receptor blockers (ARBs) prevent aneurysm formation in MFS mouse models. In patients, ARBs only slow down aortic dilation.

Lack of functional TCR-epitope interaction is associated with herpes zoster through reduced downstream T cell activation.

The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4 T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients.