A5065704289- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Atherosclerosis and Cardiovascular Diseases
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Liver Diseases and Immunity
- Gut microbiota and health
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Inflammatory Bowel Disease
- Diabetes and associated disorders
- Immune cells in cancer
- Genetic factors in colorectal cancer
- COVID-19 Clinical Research Studies
- Mitochondrial Function and Pathology
- Gene Regulatory Network Analysis
- Clinical Nutrition and Gastroenterology
- Cardiac Fibrosis and Remodeling
- Metal complexes synthesis and properties
- SARS-CoV-2 and COVID-19 Research
- Microscopic Colitis
- Adipokines, Inflammation, and Metabolic Diseases
University Medical Center Groningen
2014-2025
University of Groningen
2014-2025
University of California, San Francisco
2021-2024
University Medical Center Utrecht
2024
Ludwig-Maximilians-Universität München
2024
German Centre for Cardiovascular Research
2024
Technical University of Munich
2024
Dialyse Centrum Groningen
2015-2023
Oncode Institute
2020-2022
Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the caused by severe acute respiratory syndrome 2 (SARS-CoV-2). However, prevalence of these antibodies, their longitudinal dynamics across severity scale, and functional effects on circulating leukocytes remain unknown. Here, 284 COVID-19, we IFN–specific peripheral blood samples from 19% 6% disease. We no IFN individuals moderate Longitudinal...
In recent years, functional genomics approaches combining genetic information with bulk RNA-sequencing data have identified the downstream expression effects of disease-associated risk factors through so-called quantitative trait locus (eQTL) analysis. Single-cell creates enormous opportunities for mapping eQTLs across different cell types and in dynamic processes, many which are obscured when using methods. Rapid increase throughput reduction cost per now allow this technology to be applied...
Abstract The host’s gene expression and regulatory response to pathogen exposure can be influenced by a combination of the genetic background, type time pathogens. Here we provide detailed dissection this using single-cell RNA-sequencing 1.3M peripheral blood mononuclear cells from 120 individuals, longitudinally exposed three different These analyses indicate that cell-type-specificity is more prominent factor than pathogen-specificity regarding contexts affect how genetics influences...
Abstract The average length of telomere repeats (TL) declines with age and is considered to be a marker biological ageing. Here, we measured TL in six blood cell types from 1046 individuals using the clinically validated Flow-FISH method. We identified remarkable cell-type-specific variations TL. Host genetics, environmental, parental intrinsic factors such as sex, age, smoking are associated By analysing genome-wide methylation patterns, that association maternal, but not paternal, mediated...
Abstract Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of cellular landscape organs. Most single-cell protocols require fresh material, which limits sample size per experiment, and consequently, introduces batch effects. This is especially true for samples acquired through complex medical procedures, such as intestinal mucosal biopsies. Moreover, tissue dissociation procedure required obtaining single cells a major source noise; different procedures applied to...
Abstract Acute and chronic coronary syndromes (ACS CCS) are leading causes of mortality. Inflammation is considered a key pathogenic driver these diseases, but the underlying immune states their clinical implications remain poorly understood. Multiomic factor analysis (MOFA) allows unsupervised data exploration across multiple types, identifying major axes variation associating with molecular processes. We hypothesized that applying MOFA to multiomic obtained from blood might uncover hidden...
Background. Intestinal transplantation is the treatment for patients with irreversible intestinal failure and complications of parenteral nutrition. Five-year graft survival only 56%, possibly due to an imbalance in immunosuppression, aiming prevent rejection while maintaining protection against pathogens. Studying graft’s mucosal cell populations regulation donor recipient cells posttransplantation offers a unique opportunity address this (im)balance leading rejection. Methods. We performed...
Abstract Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also mitochondrial (mtDNA) is subjective to methylation. This includes demonstration of mitochondria-localised methyltransferases demethylases, detection mtDNA methylation as well hydroxymethylation. Importantly, differential has been linked aging diseases, including cancer diabetes. However, functionality not demonstrated. Therefore, we targeted methylating enzymes (modifying...
Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which likely mask cell type-context regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified subpopulations, current methods do labor-intensive expensive. We introduce a new method, Decon2, framework for...
The immune system's role in ST-segment-elevated myocardial infarction (STEMI) remains poorly characterized but is an important driver of recurrent cardiovascular events. While anti-inflammatory drugs show promise reducing recurrence risk, their broad system impairment may induce severe side effects. To overcome these challenges, a nuanced understanding the response to STEMI needed.
Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, functional effects on circulating leukocytes remain unknown. Here, 284 patients, we IFN-I 19% of critical, 6% severe none moderate cases. Longitudinal profiling over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope transcriptome sequencing from 54 15 non-COVID-19...
Abstract Dexamethasone is the standard of care for critically ill patients with COVID-19, but mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk single-cell RNA sequencing samples from lower respiratory tract blood, assess plasma cytokine profiling to study dexamethasone on both systemic pulmonary immune cell compartments. In blood samples, associated decreased expression genes T activation, including TNFSFR4...
DNA hypermethylation is extensively explored as therapeutic target for gene expression modulation in cancer. Here, we re-activated hypermethylated candidate tumor suppressor genes (TSGs) (C13ORF18, CCNA1, TFPI2, and Maspin) by TET2-induced demethylation cervical cancer cell lines. To redirect TET2 to TSGs, engineered zinc finger proteins (ZFPs), which were first fused the transcriptional activator VP64 validate effective re-expression confirm TSG function. ChIP-Seq not only revealed enriched...
Epigenetic silencing of tumor suppressor genes (TSGs) is considered a significant event in the progression cancer. For example, EPB41L3, potential biomarker cervical cancer, often silenced by cancer-specific promoter methylation. Artificial transcription factors (ATFs) are unique tools to re-express such TSGs functional levels; however, induced effects transient. Here, we aimed improve efficiency and sustainability gene re-expression using engineered zinc fingers fused VP64 (ZF-ATFs) or DNA...
Metal coordination complexes can display interesting biological activity, as illustrated by the bleomycins (BLMs), a family of natural antibiotics that when coordinated to redox-active metal ion, show antitumor activity. Yet, which ion is required for activity in cells still subject debate. In this study, we described how different ions affect intracellular behavior and synthetic BLM-mimic N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine (N4Py). Our study shows mixture iron(II),...
Candida bloodstream infection, i.e. candidemia, is the most frequently encountered life-threatening fungal infection worldwide, with mortality rates up to almost 50%. In majority of candidemia cases, albicans responsible. Worryingly, a global increase in number patients who are susceptible (e.g. immunocompromised patients), has led rise incidence last few decades. Therefore, better understanding anti-Candida host response essential overcome this poor prognosis and lower disease incidence....
Cancer cachexia is a devastating chronic condition characterized by involuntary weight loss, muscle wasting, abnormal fat metabolism, anorexia, and fatigue. However, the molecular mechanisms underlying this syndrome remain poorly understood. In particular, hypothalamus may play central role in cachexia, given that it has direct access to peripheral signals because of its anatomical location attenuated blood–brain barrier. Furthermore, region critical regulating appetite metabolism. To...
Iron complexes of N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)-methylamine (N4Py) have proven to be excellent synthetic mimics the Bleomycins (BLMs), which are a family natural antibiotics used clinically in treatment certain cancers. However, most investigations DNA cleavage activity these and related metal were carried out cell-free systems using plasmid as substrate. The present study evaluated nuclear cell cytotoxicity BLM its based on ligand N4Py. N4Py-based reagents induced living cells...