Viral induced polyarthritis by Chikungunya

PROJECT OVERVIEW

Chikungunya (CHIK) is an alphavirus which is a mosquito-borne viral disease with recent outbreaks across Africa, Asia and south America that can lead to a painful polyarthritis in patients. The mechanism driving this inflammatory disease pathology in human joint synovium is unknown and the relationships to different joint arthropathies including Juvenile Idiopathic Arthritis, Rheumatoid Arthritis, Osteoarthritis, Psoriatic Arthritis and therapy induced inflammatory arthritis.  Using tissue biopsies and patient blood samples combined with single cell biology including single cell RNA sequencing, spatial protein and transcriptome imaging and serum protein analysis this project will apply a systems-based approach to provide insights disease mechanisms. These will include analysis of the T cell and B cell repertoire in infiltrating adaptive immune cells and the gene transcriptome of innate immune cells (monocytes, macrophage & neutrophils) and tissue microenvironment including fibroblasts and endothelium.  The long-term aim of this project is to provide a rational basis for treatments for CHIK induced polyarthritis and provide new insights into mechanisms driving the range of immune mediated inflammatory joint pathologies found in humans. 

KEYWORDS

Chronic inflammation, arthritis, viral infection, single cell biology, systems immunology

TRAINING OPPORTUNITIES

The applicant will gain key experience in human tissue biology processing and systems immunology including single cell biology and spatial transcriptomics. 

KEY PUBLICATIONS

Bolton C, Mahony CB, Clay E, Nisa PR, Lomholt S, Hackland A, Chin PS, Smith CG, Alexiou V, Nguyen HD, Thyagarajan M, Shiekh Z, Davis P, Chippington S, Compeyrot-Lacassagne S, Davda S, Foley C, Turtsevich I, Ingledow B, Kupiec K, Kelly J, Hanlon MM, DiCarlo E, Jones LJ, Smith SL, Eyre S, Neag G, Kemble S, Madhu R, Palshikar MG, Korsunsky I, Gao C, Tran M, Dendrou C, Buckley CD, Coles MCC, Raza K,MAPJAG Study Group, Gravallese E, Filer A, Wei K, Eslam, Al-Abadi W, Rosser EC, Wedderburn LR Croft AP, Severity-associated molecular niches define the inflamed synovium in juvenile idiopathic 1 arthritis, in press, Science Translational Medicine. 2025 Jul 2;17(805):eadt6050. doi: 10.1126/scitranslmed.adt6050

Drennan GD, Provine NM, Harris SA, Otter A, Hollett J, Cooper C, De Maeyer RPH, Nassanga B, Ateere A, Pudjohartono MF, Peng Y, Chen JL, Jones J, Fadzillah NHM, Grifoni A, Sette A, Satti I, Murray SM, Cathy Rowe C, Mandal S, Hallis B, Klenerman P, Dong T, Richards D, James Fullerton J, McShane H, Coles MC, Immunogenicity of MVA-BN vaccine deployed as mpox prophylaxis: a prospective cohort study and analysis of transcriptomic predictors of response. Lancet Microbe, in press 2025.

Thomas T, Friedrich M, Rich-Griffin C, Mathilde Pohin M, Devika Agarwa1 D, Pakpoor J, Lee C, Tandon R, Rendek A, Aschenbrenner D, Jainarayanan A, Voda A, Siu J, Sanches-Peres R, Nee E, Sathananthan D, Kotliar D, Peter Todd P, Kiourlappou M, Gartner L, Nicholas Ilott N, Issa F, Hester J, Jason Turner11, Nayar S, Mackerodt J, IBD Cohort Investigators, AMP RA investigators, Zhang F, Jonsson A, Brenner M, Raychaudhuri S, Kulicke R, Ramsdell D, Stransky N, Pagliarini R, Bielecki P, Spies N, Marsden B,Taylor S, Wagner A, Klenerman P, Walsh A, Coles M, Jostins-Dean L, Powrie FM, Filer A, Travis S, Uhlig HH, Dendrou C, Buckley CD, A longitudinal single-cell therapeutic atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease, Nature Immunology, 2024.

Ng MTH, Borst R, Gacaferi H, Davidson S, Ackerman JE, Johnson PA, Machado CC, Reekie I, Attar M, Windell D, Kurowska-Stolarska M, MacDonald L, Alivernini S, Garvilles M, Jansen K, Bhalla A, Lee A, Charlesworth J, Chowdhury R, Klenerman P, Powell K, Hackstein CP; ICECAP Consortium; Furniss D, Rees J, Gilroy D, Coles M, Carr AJ, Sansom SN, Buckley CD, Dakin SG. A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution. Nature Communications, 2024 Feb 19;15(1):1394. doi: 10.1038/s41467-024-45341-9. 

THEMES

Experimental Medicine, immunology, inflammation, systems biology

CONTACT INFORMATION OF ALL SUPERVISORS:

mark.coles@kennedy.ox.ac.uk

christopher.buckley@kennedy.ox.ac.uk

calliope.dendrou@kennedy.ox.ac.uk

sarah.davidson@kennedy.ox.ac.uk