Dominik Aschenbrenner

Dominik Aschenbrenner
Novartis Institutes for BioMedical Research | NIBR · Autoimmunity, Transplantation and Inflammatory (ATI) Disease Group

Dr.sc.

About

43
Publications
7,823
Reads
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1,468
Citations
Citations since 2017
41 Research Items
1108 Citations
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2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
Additional affiliations
April 2022 - present
Novartis Institutes for BioMedical Research
Position
  • Principal Scientist
September 2015 - present
University of Oxford
Position
  • PostDoc Position
Description
  • Mucosal Immunology
April 2011 - August 2015
Institute for Research in Biomedicine
Position
  • PhD Student
Education
April 2011 - August 2015
ETH Zurich
Field of study
  • Immunology and Microbiology
October 2001 - October 2010
University of Vienna
Field of study
  • Microbiology/Genetics

Publications

Publications (43)
Article
Full-text available
Balancing natural selection is a process by which genetic variants arise in populations that are beneficial to heterozygous carriers, but pathogenic when homozygous. We systematically investigated the prevalence, structural, and functional consequences of pathogenic IL10RA variants that are associated with monogenic inflammatory bowel disease. We i...
Article
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Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking. The mechanism for Crohn’s disease-like inflammation, lung fibrosis, and macrophage lipid accumulation in these patients remains enigmatic. The aim of this study is to understand the cellular basis of inflammation in HPS-1. We performed mass cytometry, proteom...
Article
Full-text available
The gut mycobiome (fungi) is a small but crucial component of the gut microbiome in humans. Intestinal fungi regulate host homoeostasis, pathophysiological and physiological processes, and the assembly of the co-residing gut bacterial microbiome. Over the past decade, accumulating studies have characterised the gut mycobiome in health and several p...
Article
Full-text available
Background Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven va...
Article
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Cell-cell communication is mediated by many soluble mediators, including over 40 cytokines. Cytokines, e.g. TNF, IL1 β , IL5, IL6, IL12 and IL23, represent important therapeutic targets in immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD), psoriasis, asthma, rheumatoid and juvenile arthritis. The identification...
Article
Full-text available
Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatur...
Article
Full-text available
Background and aims Monogenic forms of inflammatory bowel disease (IBD) illustrate the essential roles of individual genes in pathways and networks safeguarding immune tolerance and gut homeostasis. Methods To build a taxonomy model we assessed 165 disorders. Genes were prioritized based on penetrance of IBD and disease phenotypes were integrated...
Preprint
Full-text available
Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune sig...
Article
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Spleen tyrosine kinase (SYK) is a critical immune signaling molecule and therapeutic target. We identified damaging monoallelic SYK variants in six patients with immune deficiency, multi-organ inflammatory disease such as colitis, arthritis and dermatitis, and diffuse large B cell lymphomas. The SYK variants increased phosphorylation and enhanced d...
Article
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Background : Angiotensin I converting enzyme 2 (ACE2) is a receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and differences in its expression may affect susceptibility to infection. Methods : We performed a genome-wide expression quantitative trait loci (eQTL) analysis using hepatitis C virus-infected liver tissue from...
Article
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The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6ST (p.R281Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as...
Article
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Objective: Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine. Design: We...
Article
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Background: Traditionally, the transcriptomic and proteomic characterisation of CD4+ T cells at the single-cell level has been performed by two largely exclusive types of technologies: single-cell RNA sequencing (scRNA-seq) and antibody-based cytometry. Here, we present a multi-omics approach allowing the simultaneous targeted quantification of mR...
Article
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Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven differe...
Preprint
Full-text available
The SARS-CoV-2 pandemic has resulted in widespread morbidity and mortality globally, but with widely variable outcomes. The development of severe disease and mortality is higher in older individuals, males and those with other co-morbidities, and may vary across ethnic groups. However, so far, no host genetic factor has been clearly associated with...
Article
Full-text available
Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven differe...
Article
Full-text available
The gene IL6ST encodes GP130, the common signal transducer of the IL-6 cytokine family consisting of 10 cytokines. Previous studies have identified cytokine-selective IL6ST defects that preserve LIF signaling. We describe three unrelated families with at least five affected individuals who presented with lethal Stüve-Wiedemann-like syndrome charact...
Preprint
Full-text available
BACKGROUND & AIMS Dysregulated immune responses are the cause of inflammatory bowel diseases. Studies in both mice and humans suggest a central role of IL-23 producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for select IL-23 targeting therapies as part of personalized medici...
Preprint
Full-text available
The transcriptomic and proteomic characterisation of CD4+ T cells at the single-cell level has been performed traditionally by two largely exclusive types of technologies: single cell RNA-sequencing (scRNA-seq) technologies and antibody-based cytometry. Here we demonstrate that the simultaneous targeted quantification of mRNA and protein expression...
Article
Full-text available
In the version of this article initially published, in the legend to Fig. 1b, the description of the frequency of TH17-IL-10⁺ clones was incomplete for the first group; this should read as follows: “..13 experiments with clones isolated from CCR6⁺CCR4⁺CXCR3– T cells..”. Also, the label along the vertical axis of the bottom right plot in Figure 5b w...
Article
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Hyper-IgE syndromes comprise a group of inborn errors of immunity. STAT3-deficient hyper-IgE syndrome is characterized by elevated serum IgE levels, recurrent infections and eczema, and characteristic skeletal anomalies. A loss-of-function biallelic mutation in IL6ST encoding the GP130 receptor subunit (p.N404Y) has very recently been identified in...
Article
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Different types of effector and memory T lymphocytes are induced and maintained in protective or pathological immune responses. Here we characterized two human CD4+ TH17 helper cell subsets that, in the recently activated state, could be distinguished on the basis of their expression of the anti-inflammatory cytokine IL-10. IL-10+ TH17 cells upregu...
Article
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We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ⁺IL-17⁺ (TH1/17) and IFN-γ⁻IL-17⁺ (TH17) CD4⁺ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared...
Article
Full-text available
Multiple cytokines, including interleukin (IL)-6, IL-11, IL-27, oncostatin M (OSM) and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine receptor subunit. We describe a patient with a homozygous mutation of IL6ST (encoding GP130 p.N404Y) who presented with recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, de...
Article
T helper (TH) cell polarization during priming is modulated by a number of signals, but whether polarization to a given phenotype also influences recall responses of memory TH cells is relatively unknown. Here we show that miR-181a is selectively induced in both human and mouse naive T cells differentiating into the TH17, but not TH1 or TH2 subset....
Article
Full-text available
IL-17-producing CD4+ T helper cells (TH17) have been extensively investigated in mouse models of autoimmunity. However, the requirements for differentiation and the properties of pathogen-induced human TH17 cells remain poorly defined. Using an approach that combines the in vitro priming of naive T cells with the ex vivo analysis of memory T cells,...

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Projects

Projects (3)
Project
To describe and understand the functions and mechanisms of single genes in human primary immunodeficiencies.