David R. Willé
GeneGenome-wide association studyEnhancerCancerInternal medicineDisease gene identificationChemokineEndocrinologySomatic cellCellNeuroscienceGenomicsImmunologyT cellNaltrexoneSelf-administrationCytokineBrain-derived neurotrophic factorDiseaseNicotineOpioid receptorBiological networkR packageCancer genomeOpen sourceComputer scienceProteomicsAlzheimer's diseaseGeneticsComputational biologyMedicineDrug discoveryIdentification (information)ChromatinBenchmarkingBiologyImmune systemCell biologyPharmacologyBiological pathway
Publications 20
#1Eddie Cano-GamezH-Index: 5
#2Blagoje SoskicH-Index: 6
Last. Gosia TrynkaH-Index: 43
view all 15 authors...
Naive CD4(+) T cells coordinate the immune response by acquiring an effector phenotype in response to cytokines. However, the cytokine responses in memory T cells remain largely understudied. Here we use quantitative proteomics, bulk RNA-seq, and single-cell RNA-seq of over 40,000 human naive and memory CD4(+) T cells to show that responses to cytokines differ substantially between these cell types. Memory T cells are unable to differentiate into the Th2 phenotype, and acquire a Th17-like phenot...
#1Blagoje SoskicH-Index: 6
#2Eddie Cano-GamezH-Index: 5
Last. Gosia TrynkaH-Index: 43
view all 12 authors...
Immune-disease-associated variants are enriched in active chromatin regions of T cells and macrophages. However, whether these variants function in specific cell states is unknown. Here we stimulated T cells and macrophages in the presence of 13 cytokines and profiled active and open chromatin regions. T cell activation induced major chromatin remodeling, while the presence of cytokines fine-tuned the magnitude of changes. We developed a statistical method that accounts for subtle changes in the...
#1Sergio Picart-Armada (UPC: Polytechnic University of Catalonia)H-Index: 6
#2Steven J. BarrettH-Index: 2
Last. Benoit H. DessaillyH-Index: 18
view all 6 authors...
In-silico identification of potential target genes for disease is an essential aspect of drug target discovery. Recent studies suggest that successful targets can be found through by leveraging genetic, genomic and protein interaction information. Here, we systematically tested the ability of 12 varied algorithms, based on network propagation, to identify genes that have been targeted by any drug, on gene-disease data from 22 common non-cancerous diseases in OpenTargets. We considered two biolog...
#6Ultan McDermott (Wellcome Trust Sanger Institute)H-Index: 61
Cancer hallmarks are evolutionary traits required by a tumour to develop. While extensively characterised, the way these traits are achieved through the accumulation of somatic mutations in key biological pathways is not fully understood. To shed light on this subject, we characterised the landscape of pathway alterations associated with somatic mutations observed in 4,415 patients across ten cancer types, using 374 orthogonal pathway gene-sets mapped onto canonical cancer hallmarks. Towards thi...
#1Tamzin L. Ripley (University of Sussex)H-Index: 19
#2Sandra Sanchez-Roige (University of Sussex)H-Index: 25
Last. David N. Stephens (University of Sussex)H-Index: 59
view all 9 authors...
Rationale Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice.
#1James T. Teo (UCL: University College London)H-Index: 28
#2G. Bentley (GSK: GlaxoSmithKline)H-Index: 8
Last. Pradeep J. Nathan (University of Cambridge)H-Index: 63
view all 12 authors...
The brain-derived neurotropic factor (BDNF) Val66Met polymorphism has been associated with abnormalities of synaptic plasticity in animal models, and abnormalities in motor cortical plasticity have also been described in humans using transcranial direct current stimulation. No study has yet been done on plasticity in non-motor regions, and the effect of two Met alleles (i.e. ‘Met dose’) is not well understood. We studied the effect of the BDNF Val66Met polymorphism on the after-effects of transc...
#1Fruzsina Soltesz (GSK: GlaxoSmithKline)H-Index: 4
#2John Suckling (University of Cambridge)H-Index: 102
Last. Pradeep J. Nathan (University of Cambridge)H-Index: 63
view all 16 authors...
Increasing evidence suggests that synaptic dysfunction is a core pathophysiological hallmark of neurodegenerative disorders. Brain-derived neurotropic factor (BDNF) is key synaptogenic molecule and targeting synaptic repair through modulation of BDNF signalling has been suggested as a potential drug discovery strategy. The development of such “synaptogenic” therapies depend on the availability of BDNF sensitive markers of synaptic function that could be utilized as biomarkers for examining targe...
#1Chiara Giuliano (University of Cambridge)H-Index: 12
#2Trevor W. Robbins (University of Cambridge)H-Index: 256
Last. Barry J. Everitt (University of Cambridge)H-Index: 149
view all 5 authors...
Rationale Evidence has implicated the endogenous opioids, in particular μ-opioid receptors, in emotional behavior and regulation of reward circuits, especially in the context of heroin addiction and hedonic responses to ingestive rewards. The μ-opioid receptor antagonist naltrexone (NTX) has been reported to be effective in preventing relapse to alcoholism and in reducing alcohol and cocaine craving during abstinence.
#1Nikola Marjanović (GSK: GlaxoSmithKline)H-Index: 7
#2Martina Bosnar (GSK: GlaxoSmithKline)H-Index: 11
Last. Vesna Eraković Haber (GSK: GlaxoSmithKline)H-Index: 18
view all 10 authors...
Abstract Macrolide antibiotics are known to exert anti-inflammatory actions in vivo , including certain effects in COPD patients. In order to investigate the immunomodulatory profile of activity of macrolide antibiotics, we have studied the effects of azithromycin, clarithromycin, erythromycin and roxithromycin on the in vitro production of a panel of inflammatory mediators from cells isolated from human, steroid-naive, COPD sputum samples. Macrolide effects were compared to three other commonly...
#1Enrico Domenici (GSK: GlaxoSmithKline)H-Index: 47
#2David R. Willé (GSK: GlaxoSmithKline)H-Index: 13
Last. Pierandrea Muglia (GSK: GlaxoSmithKline)H-Index: 62
view all 16 authors...
Despite significant research efforts aimed at understanding the neurobiological underpinnings of psychiatric disorders, the diagnosis and the evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms. Therefore, biological markers which could improve the current classification of psychiatry disorders, and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. In order t...
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