Daniel Muthas
A5053644742- Asthma and respiratory diseases
- Computational Drug Discovery Methods
- Chronic Obstructive Pulmonary Disease (COPD) Research
- IL-33, ST2, and ILC Pathways
- Cancer therapeutics and mechanisms
- Tuberculosis Research and Epidemiology
- Genetic Associations and Epidemiology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Eosinophilic Esophagitis
- Genomics and Rare Diseases
- Neonatal Respiratory Health Research
- Eosinophilic Disorders and Syndromes
- Pharmacogenetics and Drug Metabolism
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Protein Structure and Dynamics
- Epigenetics and DNA Methylation
- Systemic Lupus Erythematosus Research
- Pediatric health and respiratory diseases
- Microscopic Colitis
- Lung Cancer Treatments and Mutations
- Pharmacological Effects of Natural Compounds
- Inhalation and Respiratory Drug Delivery
- Immune Cell Function and Interaction
- Inflammation biomarkers and pathways
AstraZeneca (Sweden)
2016-2025
AstraZeneca (Finland)
2025
Medizinische Hochschule Hannover
2019
Fraunhofer Institute for Toxicology and Experimental Medicine
2019
Uppsala University
2005-2013
AstraZeneca (United Kingdom)
2013
University of Dundee
2011
Abstract Genome-wide association studies have uncovered thousands of common variants associated with human disease, but the contribution rare to disease remains relatively unexplored. The UK Biobank contains detailed phenotypic data linked medical records for approximately 500,000 participants, offering an unprecedented opportunity evaluate effect variation on a broad collection traits 1,2 . Here we study relationships between protein-coding and 17,361 binary 1,419 quantitative phenotypes...
Integrating human genomics and proteomics can help elucidate disease mechanisms, identify clinical biomarkers discover drug targets1-4. Because previous proteogenomic studies have focused on common variation via genome-wide association studies, the contribution of rare variants to plasma proteome remains largely unknown. Here we associations between protein-coding 2,923 protein abundances measured in 49,736 UK Biobank individuals. Our variant-level exome-wide study identified 5,433...
Introduction Anifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using longitudinal transcriptomic and proteomic analyses 52-week, randomised, phase 3 TULIP-1 TULIP-2 trials. Methods Patients moderate to severe SLE were enrolled in received intravenous or placebo alongside standard therapy. Whole-blood expression 18 017 genes...
Telomeres protect chromosome ends from damage and their length is linked with human disease aging. We developed a joint telomere metric, combining quantitative PCR whole-genome sequencing measurements 462,666 UK Biobank participants. This metric increased SNP heritability, suggesting that it better captures genetic regulation of length. Exome-wide rare-variant gene-level collapsing association studies identified 64 variants 30 genes significantly associated length, including allelic series...
Judging if a protein is able to bind orally available molecules with high affinity, i.e. druggable, an important step in target assessment. In order derive structure-based method predict druggability, comprehensive, nonredundant data set containing crystal structures of 71 druggable and 44 less proteins was compiled by literature search mining. This subsequently used train druggability predictor (DrugPred) using partial least-squares projection latent discriminant analysis (PLS-DA). DrugPred...
Drug-induced liver injury (DILI) is a major cause of failed drug development, withdrawal and restricted usage. Therefore screening assays which aid selection candidate drugs with reduced propensity to DILI are required. We have investigated the toxicity 144 drugs, 108 caused DILI, using identified in literature as having some predictivity for hepatotoxicity. The validated utilised either HepG2 cells, cells presence rat S9 fraction or isolated human hepatocytes. All parameters were quantified...
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite substantial progress, the genetic determinants of this disease remain incompletely defined. Using whole genome and exome sequencing data from 752 individuals with sporadic IPF 119,055 UK Biobank controls, we performed variant-level exome-wide association study (ExWAS) gene-level collapsing analyses. Our analysis revealed novel between rare missense variant in...
Abstract Utilizing Baird's theory on triplet state aromaticity, we show that the singlet–triplet energy gaps (Δ E ST ) of pentafulvenes are easily varied through substitution by as much 36 kcal mol −1 . This exploits fact fulvenes act aromatic chameleons in which dipoles reverse going from singlet ground (S 0 to lowest ππ* (T 1 ); thus, their electron distributions adapted so achieve some aromaticity both states. The results based quantum chemical calculations with OLYP density functional...
Although gut bacterial dysbiosis is recognized as a regulator of beta-cell autoimmunity, no data available on fungal in the children at risk type 1 diabetes (T1D). We hypothesized that co-occurrence and contributes to intestinal inflammation autoimmune destruction insulin-producing beta-cells T1D. Fecal blood samples were collected from 26 tested positive for least one diabetes-associated autoantibody (IAA, GADA, IA-2A or ICA) matched autoantibody-negative with HLA-conferred susceptibility...
This paper challenges the general desire to find simple rules and guidelines reduce attrition due toxicity clinical safety. We present an analysis of 150 AstraZeneca development compounds evaluate some published their ability identify with safety liabilities. Interestingly, none current were able discriminate that successfully reached Phase II. The was extended recently approved drugs (2009–2011) we found a large portion did not comply would never have patients if such had been applied at...
Abstract Background Chronic obstructive pulmonary disease (COPD) patients are at increased risk of poor outcome from Coronavirus (COVID-19). Early data suggest elevated Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) receptor angiotensin converting enzyme (ACE2) expression, but relationships to phenotype and downstream regulators inflammation in the Renin-Angiotensin system (RAS) unknown. We aimed determine relationship between RAS gene expression relevant SARS-CoV-2 infection lung with...
Abstract Background Crohn’s Disease (CD) is a chronic condition that can impact any part of the gastrointestinal tract. The sustained inflammation driven by continuous influx inflammatory leukocytes into gut mucosa, which regulated through chemokine gradients and adhesion molecules, including integrins. In gut, migration cells to specific segments thought be mediated selected integrins and/or axes. CCL25/CCR9 axis has been identified as key pathway for immune cell small bowel segments, such...
Abstract Background The role of eosinophils in COPD and their utility as biomarkers for cytokine targeting monoclonal therapies remains unclear. We investigated the distribution across different tissue compartments analysed gene expression to understand possible mechanistic drivers eosinophilic inflammation COPD. Methods Blood BAL from ex-smoking volunteers with mild/moderate (n = 31) healthy controls 20), bronchial biopsy a subcohort 19 n 8, respectively) was analysed....
Based on an imidazo[1,2-a]pyridine hit from a high-throughput screening directed at the M. tuberculosis enzyme glutamine synthetase, expansion was performed by synthesizing number of analogs. A set 16 molecules first synthesized according to statistical molecular design approach. One potent inhibitor identified (IC50 = 3.0 μM), which led synthesis 17 additional imidazo[1,2-a]pyridines in follow-up study. Among these, several inhibitors were with single-digit micromolar potency and one...
Abstract Bleomycin hydrolase (BLMH) is a well-conserved cysteine protease widely expressed in several mammalian tissues. In skin, which contains high levels of BLMH, this involved the degradation citrullinated filaggrin monomers into free amino acids important for skin hydration. Interestingly, expression and activity BLMH reduced patients with atopic dermatitis (AD) psoriasis, knockout mice acquire tail dermatitis. Apart from its already known function, we have discovered novel role...