Mark Coles
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Quantitative Systems Pharmacology Models of Anti‐Amyloid Treatments for Alzheimer’s Disease: A Systematic Review Open
Background Quantitative systems pharmacology (QSP) models have emerged as useful tools for evaluating and understanding the efficacy of therapies for Alzheimer’s disease (AD). Bringing together a clinical focus with the mechanistic detail …
Early lymph node T follicular helper cell signalling hub drives influenza vaccine response in an ancestrally diverse cohort Open
The study was funded by the Silicon Valley Community Foundation with a Chan Zuckerberg Initiative donation. The funder had no role in the study design, data analysis or decision to publish. The funder provided infrastructure support for th…
View article: The ontogeny of myeloid-stromal synovial tissue niches in rheumatoid arthritis
The ontogeny of myeloid-stromal synovial tissue niches in rheumatoid arthritis Open
Recent single-cell multi-omic and spatial analyses of synovial biopsies have transformed our understanding of myeloid cell–driven mechanisms underlying human joint pathology and tissue homeostasis in Rheumatoid arthritis (RA). However, the…
View article: The ontogeny of myeloid-stromal synovial tissue niches in rheumatoid arthritis
The ontogeny of myeloid-stromal synovial tissue niches in rheumatoid arthritis Open
Recent single-cell multi-omic and spatial analyses of synovial biopsies have transformed our understanding of myeloid cell–driven mechanisms underlying human joint pathology and tissue homeostasis in Rheumatoid arthritis (RA). However, the…
View article: Synovial tissue atlas in juvenile idiopathic arthritis reveals pathogenic niches associated with disease severity
Synovial tissue atlas in juvenile idiopathic arthritis reveals pathogenic niches associated with disease severity Open
Precision application of targeted therapies is urgently needed to improve long-term clinical outcomes for children affected by inflammatory arthritis, known as juvenile idiopathic arthritis (JIA). Progress has been hampered by our limited …
Ex vivo model of functioning human lymph node reveals role for innate lymphocytes and stroma in response to vaccine adjuvant Open
Immunological processes that underpin human immune responses to therapeutics and vaccine components, such as vaccine adjuvants, remain poorly defined due to a paucity of models that faithfully recapitulate immune activation in lymphoid tis…
View article: An end-to-end framework for Cell DIVE multiplexed imaging and spatial immune microenvironment analysis
An end-to-end framework for Cell DIVE multiplexed imaging and spatial immune microenvironment analysis Open
Summary This paper describes an end-to-end workflow for highly multiplexed fluorescence imaging with the Cell DIVE platform, allowing simultaneous detection of 40+ markers at single-cell resolution. Combining whole-slide multiplexed imagin…
View article: Tissue resident memory T cells populate the human uveal tract
Tissue resident memory T cells populate the human uveal tract Open
The current concept is that the eye is an immune privileged site endowed with innate immune regulatory networks to maintain organ function. We now have evidence that resident T cells occupy intraocular tissues. In immune-mediated inflammat…
T cell memory response to MPXV infection exhibits greater effector function and migratory potential compared to MVA-BN vaccination Open
In 2022, a global mpox outbreak occurred, and remains a concern today. The T cell memory response to MPXV (monkeypox virus) infection has not been fully investigated. In this study, we evaluate this response in convalescent and MVA-BN (Mod…
View article: Immunogenicity of MVA-BN vaccine deployed as mpox prophylaxis: a prospective, single-centre, cohort study and analysis of transcriptomic predictors of response
Immunogenicity of MVA-BN vaccine deployed as mpox prophylaxis: a prospective, single-centre, cohort study and analysis of transcriptomic predictors of response Open
UKRI via the UK Monkeypox Research Consortium, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the Kennedy Trust for Rheumatology Research, the John Climax Donation, the Medical Research Council (UK), the Wellcome…
Lipopolysaccharide lateral mobility in the Gram-negative bacterial outer membrane is confined and governed by interactions within the conserved Lipid A anchor Open
The Gram-negative bacterial cell envelope is defined by an asymmetric outer membrane where the outer leaflet adopts a highly ordered structure composed principally of lipopolysaccharide molecules. The organisation and dynamics of these gly…
View article: Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome
Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome Open
Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal…
Applying population mechanistic modelling to find determinants of chimeric antigen receptor T-cells dynamics in month-one lymphoma patients Open
Background Chimeric antigen receptor (CAR) T-cells have been utilized for the treatment of several malignancies, including Non-Hodgkin lymphomas. A myriad of product- and patient-specific factors determines the extent of patient response, …
View article: Asparagine availability controls germinal center B cell homeostasis
Asparagine availability controls germinal center B cell homeostasis Open
The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we…
RNA editing is a molecular clock in unmodified human cells Open
Despite major advances in spatial RNA sequencing, the ability to extract temporal information in RNA sequencing experiments is still limited. Here, we describe Transcriptome Timestamping (T2), a system which harnesses naturally occurring A…
View article: Early regional lymph node activation drives influenza vaccine responses in an ancestrally diverse cohort
Early regional lymph node activation drives influenza vaccine responses in an ancestrally diverse cohort Open
Early in vivo dynamics of human immune-cell activation across regionally activated lymphoid tissue sites upon immunisation are poorly characterised in ancestrally diverse individuals. Here, we profiled draining and non-draining axillary ly…
View article: Ex vivo Model of Functioning Human Lymph Node Reveals Pivotal Role for Innate Lymphoid Cells and Stromal Populations in Response to Vaccine Adjuvant
Ex vivo Model of Functioning Human Lymph Node Reveals Pivotal Role for Innate Lymphoid Cells and Stromal Populations in Response to Vaccine Adjuvant Open
Immunological processes that underpin the administration of therapeutics and vaccines are poorly defined due to a lack of models which faithfully recapitulate human immune responses. Inbred mice lack the diversity inherent to people, while…
Cellular characterisation of advanced osteoarthritis knee synovium Open
Objectives Osteoarthritis (OA) is increasingly recognised as a whole joint disease, with an important role for synovium. However, the repertoire of immune cells and fibroblasts that constitute OA synovium remains understudied. This study a…
View article: OP0094 SPATIAL POSITIONING AND MATRIX PROGRAMS OF SYNOVIAL FIBROBLASTS UNDERPIN IMMUNE CELL ORGANISATION AND SYNOVIAL TISSUE PATHOTYPE
OP0094 SPATIAL POSITIONING AND MATRIX PROGRAMS OF SYNOVIAL FIBROBLASTS UNDERPIN IMMUNE CELL ORGANISATION AND SYNOVIAL TISSUE PATHOTYPE Open
Background Rheumatoid arthritis (RA) is highly heterogenous with distinct cellular and molecular tissue pathotypes that associate with disease outcome[1]. The synovial membrane is the primary target tissue and undergoes significant archite…
View article: A longitudinal single-cell therapeutic atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease
A longitudinal single-cell therapeutic atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease Open
Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires an understanding of how cellular networks change following therapy. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following…
View article: Asparagine availability controls B cell homeostasis
Asparagine availability controls B cell homeostasis Open
Germinal centre (GC) B cells proliferate at some of the highest rates of any mammalian cell, yet the metabolic processes which enable this are poorly understood. We performed integrated metabolomic and transcriptomic profiling of GC B cell…
Why does understanding the biology of fibroblasts in immunity really matter? Open
Fibroblasts are known for their ability to make and modify the extracellular matrix. However, there is more to them than meets the eye. It is now clear that they help define tissue microenvironments and support immune responses in organs. …
Inventory of Patient-Reported Outcome Measures Used in the Non-Operative Care of Scoliosis: A Scoping Review Open
It is unclear which patient-reported outcome measures (PROMs) can assess non-operative care for scoliosis. Most existing tools aim to assess the effects of surgery. This scoping review aimed to inventory the PROMs used to assess non-operat…
View article: Primed to resolve: A single cell atlas of the shoulder capsule reveals a cellular basis for resolving inflammatory fibrosis
Primed to resolve: A single cell atlas of the shoulder capsule reveals a cellular basis for resolving inflammatory fibrosis Open
Fibrotic conditions are a significant global disease burden. While some therapies delay disease progression, none reverse fibrosis. To gain insights into how fibrosis might resolve, we developed a comparative single cell atlas of frozen sh…
View article: In vivo human keyhole limpet hemocyanin challenge in early phase drug development: A systematic review
In vivo human keyhole limpet hemocyanin challenge in early phase drug development: A systematic review Open
Experimental exposure of healthy volunteers to the T‐cell dependent neoantigen keyhole limpet hemocyanin (KLH) permits the evaluation of immunomodulatory investigational medicinal product (IMP) pharmacology prior to the recruitment of pati…