A5010720478- Liver physiology and pathology
- Immune cells in cancer
- Liver Disease Diagnosis and Treatment
- Eosinophilic Esophagitis
- Organ Transplantation Techniques and Outcomes
- Phagocytosis and Immune Regulation
- Omental and Epiploic Conditions
- Apelin-related biomedical research
- Cutaneous lymphoproliferative disorders research
- Appendicitis Diagnosis and Management
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Liver Disease and Transplantation
- Adipokines, Inflammation, and Metabolic Diseases
- IL-33, ST2, and ILC Pathways
- Dupuytren's Contracture and Treatments
- Genetic factors in colorectal cancer
- Galectins and Cancer Biology
University of Edinburgh
2019-2024
Centre for Inflammation Research
2019-2024
The Queen's Medical Research Institute
2019-2023
Iterative liver injury results in progressive fibrosis disrupting hepatic architecture, regeneration potential, and function. Hepatic stellate cells (HSCs) are a major source of pathological matrix during thought to be functionally homogeneous population. Here, we use single-cell RNA sequencing deconvolve the mesenchyme healthy fibrotic mouse liver, revealing spatial zonation HSCs across lobule. Furthermore, show that partition into topographically diametric lobule regions, designated portal...
Abstract The liver has a unique ability to regenerate 1,2 ; however, in the setting of acute failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency transplantation as only curative option 3–5 . Here, advance understanding human regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling healthy and ALF explant livers generate single-cell, pan-lineage atlas regeneration. We uncover novel ANXA2 + migratory hepatocyte subpopulation, which...
The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides first layer of immunological defense within the abdomen. Here, we investigated mechanisms mediate capture during peritonitis. Single-cell RNA sequencing spatial analysis omental stromal cells revealed surface FALCs were covered by CXCL1+ mesothelial cells, which termed FALC cover cells. Blockade CXCL1 inhibited recruitment aggregation neutrophils at...
Dyslipidemia is a main driver of cardiovascular diseases. The ability macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism key development new treatments. Here, we investigated how adipose tissue regulate post-prandial cholesterol transport. Single-cell RNA sequencing protected bone marrow chimeras demonstrated that ingestion led specific transcriptional activation population resident...
Abstract The liver has a unique ability to regenerate 1,2 , however in the setting of acute failure (ALF) this regenerative capacity is often overwhelmed and emergency transplantation only curative option 3-5 . To advance our understanding human regeneration inform design pro-regenerative therapies, we use paired single-nuclei RNA sequencing (snRNA-seq) combined with spatial profiling healthy ALF explant livers generate first single-cell, pan-lineage atlas regeneration. We uncover novel...
Dupuytren's disease (DD) is a common, progressive fibroproliferative affecting the palmar fascia of hands, causing fingers to irreversibly flex toward palm with significant loss function. Surgical treatments are limited; therefore, effective new therapies for DD urgently required. To identify key cellular and molecular pathways driving DD, we employed single-cell RNA sequencing, profiling transcriptomes 35,250 human single cells from nonpathogenic fascia, healthy dermis. We DD-specific...
Abstract Currently there are no effective antifibrotic therapies for liver cirrhosis, a major killer worldwide. To obtain cellular resolution of directly-relevant pathogenesis and to inform therapeutic design, we profile the transcriptomes over 100,000 primary human single cells, yielding molecular definitions non-parenchymal cell types present in healthy cirrhotic liver. We uncover novel scar-associated TREM2 + CD9 macrophage subpopulation with fibrogenic phenotype, that has distinct...
Abstract The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs), which collects peritoneal contaminants and provides first layer of immunological defence within the abdomen. Using single-cell RNA sequencing spatial analysis omental stromal cells, we reveal that surface FALCs are covered with specialised mesothelial name FALC cover cells. We demonstrate CXCL1 expressed by cells critical for retention accumulation neutrophils during peritonitis. show protein...