A5041877345- Atherosclerosis and Cardiovascular Diseases
- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Immune cells in cancer
- Cardiovascular Disease and Adiposity
- CRISPR and Genetic Engineering
- Cardiomyopathy and Myosin Studies
- Inflammatory Bowel Disease
- CAR-T cell therapy research
- HIV-related health complications and treatments
- Gene Regulatory Network Analysis
- Antiplatelet Therapy and Cardiovascular Diseases
- Cancer Immunotherapy and Biomarkers
- Nuclear Receptors and Signaling
- Scientific Computing and Data Management
- Cancer-related molecular mechanisms research
- Mesenchymal stem cell research
- Platelet Disorders and Treatments
- T-cell and B-cell Immunology
- Hormonal Regulation and Hypertension
- Lipid metabolism and disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Epigenetics and DNA Methylation
University of Cambridge
2018-2025
University of Eastern Finland
2025
Cancer Research UK
2018-2025
Icahn School of Medicine at Mount Sinai
2016-2024
Wellcome Sanger Institute
2023-2024
Genomics (United Kingdom)
2024
Cancer Research UK Cambridge Center
2020-2023
Victor Chang Cardiac Research Institute
2021
Karolinska University Hospital
2018
Integrated Cardio Metabolic Centre
2018
Enrichment analysis is a popular method for analyzing gene sets generated by genome-wide experiments. Here we present significant update to one of the tools in this domain called Enrichr. Enrichr currently contains large collection diverse set libraries available and download. In total, 180 184 annotated from 102 libraries. New features have been added including ability submit fuzzy sets, upload BED files, improved application programming interface visualization results as clustergrams....
Atherosclerosis is the process underlying heart attack and stroke. Despite decades of research, its pathogenesis remains unclear. Dogma suggests that atherosclerotic plaques expand primarily via accumulation cholesterol inflammatory cells. However, recent evidence a substantial portion plaque may arise from subset "dedifferentiated" vascular smooth muscle cells (SMCs) which proliferate in clonal fashion. Herein we use multicolor lineage-tracing models to confirm mature SMC can give rise...
Although sex differences in coronary artery disease are widely accepted with women developing more stable atherosclerosis than men, the underlying pathobiology of such remains largely unknown. In disease, recent integrative systems biological studies have inferred gene regulatory networks (GRNs). Within these GRNs, key driver genes shown great promise but thus far been unidentified women.We generated sex-specific GRNs atherosclerotic arterial wall 160 and age-matched men STARNET study...
Endothelial-mesenchymal transition (EndMT) is associated with various cardiovascular diseases and in particular atherosclerosis plaque instability. However, the molecular pathways that govern EndMT are poorly defined. Specifically, role of epigenetic factors histone deacetylases (HDACs) controlling atherosclerotic phenotype remains unclear. Here, we identified deacetylation, specifically mediated by HDAC9 (a class IIa HDAC), as playing an important both atherosclerosis. Using vitro models,...
The majority of risk loci identified by genome-wide association studies (GWAS) are in non-coding regions, hampering their functional interpretation. Instead, transcriptome-wide (TWAS) identify gene-trait associations, which can be used to prioritize candidate genes disease-relevant tissue(s). Here, we aimed systematically susceptibility for coronary artery disease (CAD) TWAS. We trained prediction models nine CAD-relevant tissues using EpiXcan based on two genetics-of-gene-expression panels,...
Abstract T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation selection 1 . In humans, this process starts in early fetal development is highly active until thymic involution adolescence. To map microanatomical underpinnings of pre- postnatal stages, we established a quantitative morphological framework for thymus—the Cortico-Medullary Axis—and used it to perform spatially resolved analysis....
While our understanding of the single-cell gene expression patterns underlying transformation vascular cell types during progression atherosclerosis is rapidly improving, clinical and pathophysiological relevance these changes remains poorly understood.
Abstract Elevated plasma cholesterol and type 2 diabetes (T2D) are associated with coronary artery disease (CAD). Individuals treated cholesterol-lowering statins have increased T2D risk, while individuals hypercholesterolemia reduced risk. We explore the relationship between lipid glucose control by constructing network models from STARNET study sequencing data seven cardiometabolic tissues obtained CAD patients during by-pass grafting surgery. By integrating gene expression, genotype,...
Abstract The development of new immunotherapies to treat the inflammatory mechanisms that sustain atherosclerotic cardiovascular disease (ASCVD) is urgently needed. Herein, we present a path drug repurposing identify for ASCVD. integration time-of-flight mass cytometry and RNA sequencing identified unique signatures in peripheral blood mononuclear cells stimulated with ASCVD plasma. By comparing these large-scale gene expression data from LINCS L1000 dataset, drugs could reverse this...
Objective— A large number of genetic loci have been associated with risk coronary artery disease (CAD) through genome-wide association studies, however, for most the underlying biological mechanism is unknown. Determining molecular pathways and cellular processes affected by these will provide new insights into CAD pathophysiology may lead to therapies. The CAD-associated variants at 10p11.23 fall in JCAD , which encodes an endothelial junction protein, its function cells not known. In this...
Abstract The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics surge diseases 1,2 has fuelled efforts to catalogue cells constituting tissues health disease 3 . Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy development adulthood. We uniformly processed 385 samples from 189 controls using newly developed automated quality control approach (scAutoQC),...
Recent genome-wide association studies (GWAS) have identified multiple new loci which appear to alter coronary artery disease (CAD) risk via arterial wall-specific mechanisms. One of the annotated genes encodes LMOD1 (Leiomodin 1), a member actin filament nucleator family that is highly enriched in smooth muscle-containing tissues such as wall. However, it still unknown whether causal gene at this locus and also how associated variants expression/function CAD risk. Using epigenomic profiling...
De-differentiation and activation of pro-inflammatory pathways are key transitions vascular smooth muscle cells (SMCs) make during atherogenesis. Here, we explored the upstream regulators this 'atherogenic transition'.
T cells develop from circulating precursors, which enter the thymus and migrate throughout specialised sub-compartments to support maturation selection. This process starts already in early fetal development is highly active until involution of adolescence. To map micro-anatomical underpinnings this pre- vs. post-natal states, we undertook a spatially resolved analysis established new quantitative morphological framework for thymus, Cortico-Medullary Axis. Using axis conjunction with...
Integrating data from multiple regulatory layers across cancer types could elucidate additional mechanisms of oncogenesis. Using antibody-based protein profiling 736 cell lines, along with matching transcriptomic data, we show that pan-cancer bimodality in the amounts mRNA, protein, and phosphorylation reveals related to epithelial-mesenchymal transition (EMT). Based on bimodal expression E-cadherin, define an EMT signature consisting 239 genes, many which were not previously associated EMT....
Mesenchymal stem cells (MSCs) reportedly exist in a vascular niche occupying the outer adventitial layer. However, these have not been well characterized vivo medium- and large-sized arteries humans, their potential pathological role is unknown. To address this, healthy diseased arterial tissues were obtained as surplus surgical specimens freshly processed. We identified that CD90 marks rare population co-expresses MSC markers including PDGFRα, CD44, CD73, CD105. unlike CD90, additional...
Inflammation may contribute to an increased risk of cardiovascular disease (CVD) in HIV-1 infection. MicroRNAs (miRNAs) are involved the regulation inflammation. In treated HIV-1-infected individuals, we aimed identify differentially expressed miRNAs with known roles inflammation and CVD investigate associations between these systemic inflammation.In a screening cohort including 14 individuals 9 uninfected controls, microarray profiling was performed using peripheral blood mononuclear cells...