January Weiner
A5031475220- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immune Response and Inflammation
- Bioinformatics and Genomic Networks
- Immunodeficiency and Autoimmune Disorders
- Diagnosis and treatment of tuberculosis
- Gene expression and cancer classification
- Metabolomics and Mass Spectrometry Studies
- Dermatology and Skin Diseases
- Genomics and Phylogenetic Studies
- Biochemical and Molecular Research
- Pneumonia and Respiratory Infections
- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- interferon and immune responses
- vaccines and immunoinformatics approaches
- Cancer-related molecular mechanisms research
- Microbial Metabolic Engineering and Bioproduction
- Epigenetics and DNA Methylation
- Immune responses and vaccinations
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- Helicobacter pylori-related gastroenterology studies
- Infectious Diseases and Tuberculosis
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2020-2024
Charité - Universitätsmedizin Berlin
2011-2024
Freie Universität Berlin
2023-2024
Max Planck Institute for Infection Biology
2013-2023
Humboldt-Universität zu Berlin
2023
Max Delbrück Center
2020
Max Planck Society
2011-2016
University of Münster
2005-2011
Institute for Biodiversity
2008
University of Manchester
2005
In light of the marked global health impact tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative a persistent activation immune system and chronic inflammatory pathology active TB. Definition biosignature with unique specificity for TB demands that can differentiate diseases similar pathology, like sarcoidosis (SARC). Here, we present detailed comparison between pulmonary SARC, including whole-blood...
Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk infection Mycobacterium and progression to disease.Objectives: We investigated biosignatures predictive ability incident TB.Methods: In a case–control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort exposed household contacts, we employed RNA sequencing, PCR, pair ratio algorithm in training/test set...
General interest in the biological functions of IFN type I Mycobacterium tuberculosis (Mtb) infection increased after recent identification a distinct gene expression signature (TB) patients. Here, we demonstrate that TB-susceptible mice lacking receptor for (IFNAR1) were protected from death upon aerogenic with Mtb. Using this experimental model to mimic primary progressive pulmonary TB, dissected immune processes affected by I. IFNAR1 signaling did not affect T-cell responses, but markedly...
Successful host defense against numerous pulmonary infections depends on bacterial clearance by polymorphonuclear leukocytes (PMNs); however, excessive PMN accumulation can result in life-threatening lung injury. Local expression of CXC chemokines is critical for recruitment. The impact chemokine-dependent recruitment during Mycobacterium tuberculosis infection not fully understood. Here, we analyzed genes encoding M. tuberculosis–infected murine tissue and found that promotes upregulation...
Abstract Antigen-specific, MHC-restricted αβ T cells are necessary for protective immunity against Mycobacterium tuberculosis , but the ability to broadly study these responses has been limited. In present study, we used single-cell and bulk cell receptor (TCR) sequencing GLIPH2 algorithm analyze M. -specific sequences in two longitudinal cohorts, comprising 166 individuals with infection who progressed either ( n = 48) or controlled 118). We found 24 groups similar TCR-β sequences,...
Although tuberculosis (TB) causes more deaths than any other pathogen, most infected individuals harbor the pathogen without signs of disease. We explored metabolome >400 small molecules in serum uninfected individuals, latently healthy and patients with active TB. identified changes amino acid, lipid nucleotide metabolism pathways, providing evidence for anti-inflammatory metabolomic Metabolic profiles indicate increased activity indoleamine 2,3 dioxygenase 1 (IDO1), decreased phospholipase...
The genomic era has revealed that the large repertoire of observed animal phenotypes is dependent on changes in expression patterns a finite number genes, which are mediated by plethora transcription factors (TFs) with distinct specificities. dimerization TFs can also increase complexity genetic regulatory network manifold, combining small monomers into dimers functions. Therefore, studying evolution these dimerizing vital for understanding how increased during evolution. We focus second...
Tuberculosis remains a major health threat and its control depends on improved measures of prevention, diagnosis treatment. Biosignatures can play significant role in the development novel intervention against TB blood transcriptional profiling is increasingly exploited for their rational design. Such profiles also reveal fundamental biological mechanisms associated with pathology disease. We have compared whole gene expression patients, as well healthy infected uninfected individuals cohort...
New biomarkers of tuberculosis (TB) risk and disease are critical for the urgently needed control ongoing TB pandemic. In a prospective multisite study across Subsaharan Africa, we analyzed metabolic profiles in serum plasma from HIV-negative, TB-exposed individuals who either progressed to 3-24 months post-exposure (progressors) or remained healthy (controls). We generated trans-African biosignature TB, which identifies future progressors both on blinded test samples external data sets...
Significance Tuberculosis (TB) granulomas represent sites of both bacterial containment and tissue pathology. Macrophage killing Mycobacterium tuberculosis ( Mtb ) in to contain infection must be regulated prevent collateral damage. Nitric oxide synthase-2 (NOS2) arginase-1 (Arg1), macrophage enzymes metabolizing l -arginine, play key roles this process. NOS2 produces reactive nitrogen intermediates kill , whereas Arg1 regulates activity via substrate competition. could predominate hypoxic...
Pseudomonas aeruginosa rapidly adapts to altered conditions by quorum sensing (QS), a communication system that it uses collectively modify its behavior through the production, release, and detection of signaling molecules. QS molecules can also be sensed hosts, although respective receptors pathways are poorly understood. We describe pattern regulation in host aryl hydrocarbon receptor (AhR) is critically dependent on qualitative quantitative P. quorum. bind AhR distinctly modulate...
The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that occasionally associated with inflammatory diseases. Recent work has indicated evolutionary distinct lineages of P. play etiologic roles in disease while others are maintenance homeostasis. To shed light on the molecular basis for differential strain properties, we carried out genomic and transcriptomic analysis strains. We sequenced genome 266, type I-1a strain. Comparative 266 four other strains...
Abstract Improved tuberculosis diagnostics and tools for monitoring treatment response are urgently needed. We developed a robust simple, PCR-based host-blood transcriptomic signature, RISK6, multiple applications: identifying individuals at risk of incident disease, as screening test subclinical or clinical tuberculosis, treatment. RISK6 utility was validated by blind prediction using quantitative real-time (qRT) PCR in seven independent cohorts. Prognostic performance significantly...
There is an urgent need for new tools to combat the ongoing tuberculosis (TB) pandemic. Gene expression profiles based on blood signatures have proved useful in identifying genes that enable classification of TB patients, but thus far been complex. Using real-time PCR analysis, we evaluated from a large panel patients and healthy individuals Indian cohort. Classification models were built validated their capacity discriminate samples controls within this cohort external independent gene...
Analysis of gene set (GS) enrichment is an essential part functional omics studies. Here, we complement the established evaluation metrics GS algorithms with a novel approach to assess practical reproducibility scientific results obtained from tests when applied related data different studies.We evaluated eight and one algorithm for reproducibility, sensitivity, prioritization, false positive rate computational time. In addition algorithms, also included Coincident Extreme Ranks in Numerical...
BackgroundSince the beginning of coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading severe clinical course in patients infected with acute respiratory syndrome 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have suggested as potential genetic host factors that affect individual immune response SARS-CoV-2. We sought evaluate this hypothesis by conducting a multicenter study using HLA...
Background: Immune checkpoint inhibitor (ICI) therapy is often accompanied by immune-related pathology, with an increasing occurrence of high-risk ICI-related myocarditis. Understanding the mechanisms involved in this side effect could enable development management strategies. In mouse models, immune checkpoints, such as PD-1 (programmed cell death protein 1), control threshold self-antigen responses directed against cardiac TnI (troponin I). We aimed to identify how immunoproteasome, main...
Cellular stress has been associated with inflammation, yet precise underlying mechanisms remain elusive. In this study, various unrelated inducers were employed to screen for sensors linking altered cellular homeostasis and inflammation. We identified the intracellular pattern recognition receptors NOD1/2, which sense bacterial peptidoglycans, as general detecting perturbations of homeostasis. NOD1/2 activation upon such required generation endogenous metabolite sphingosine-1-phosphate...
The main mechanisms shaping the modular evolution of proteins are gene duplication, fusion and fission, recombination loss fragments. While a large body research has focused on duplications fusions, we concentrated, in this study, how domains lost. We investigated motif databases introduced measure protein similarity that is based domain arrangements. Proteins represented as strings comparison was classic dynamic alignment scheme. found losses were more frequent at ends proteins. showed can...
An estimated one-third of the world's population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active (TB) disease in ~5 to 10% individuals. Diagnostic and prognostic biomarkers monitor progression are urgently needed ensure better care for TB patients decrease spread TB. Biomarker development primarily based on transcriptomics. Our understanding biology combined evolving technical advances high-throughput techniques...