Elucidating T cell phenotype and function in frozen shoulder

Project overview

Frozen shoulder is a disabling condition affecting 10% of the working population. Disease causes significant pain and immobility of the shoulder joint, reducing life quality of affected patients. Frozen Shoulder is an inflammatory fibrotic disease localised to the shoulder joint capsule. Curiously the disease is self-limiting, as symptoms almost always resolve over time. Frozen shoulder is therefore a unique example of a chronic inflammatory fibrotic disease that resolves. The cellular basis underpinning how inflammatory fibrosis resolves in frozen shoulder is currently unknown. Understanding this cellular basis of resolution will 1) identify new treatments to accelerate resolution of frozen shoulder and 2) inform the biological cues to push persistent fibrotic diseases of the joint (e.g. knee arthrofibrosis) towards a resolving pathway. 

In the absence of animal models that accurately reflect this uniquely human disease, we set up ICECAP & FreeCAP clinical studies (see above links), enabling us to collect well-phenotyped patient tissues to study the cellular basis of this disease. We have identified distinct populations of T cells resident in the shoulder capsule that may play a role in the resolution of frozen shoulder¹. The over-arching aim of this project is to advance this work and elucidate the biological role of these identified T cell populations, understanding how they may contribute to the resolution of frozen shoulder. This project will further characterise T cell populations in patient tissues during health and disease and develop bespoke in vitro assays to model how T cells crosstalk with neighbouring cells in a 3D environment. In addition to discovering new therapeutic strategies for frozen shoulder, this work will also provide novel insights into the cellular mechanisms of intractable soft tissue inflammatory and fibrotic diseases affecting the lung, liver, kidney and skin which ultimately contribute to 45% of all-cause mortality², leading towards potential new treatment paradigms.

Training

The Botnar Research Centre plays host to the University of Oxford's Institute of Musculoskeletal Sciences, which enables and encourages research and education into the causes of musculoskeletal disease and their treatment. Training will be provided in techniques including scRNAseq, histology, multiplex immunohistochemistry and tissue culture utilising 2D & 3D models.

A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology, data analysis and the microbiome.  Students will also be required to attend regular seminars within the Department and those relevant in the wider University.

Students will be expected to present data regularly in Departmental seminars, the Dakin Soft Tissue Joint Disease Group and to attend external conferences to present their research globally, with limited financial support from the Department. 

Students will also have the opportunity to work closely with the Buckley, Coles & Klenerman collaborating Research Groups.

Students will have access to various courses run by the Medical Sciences Division Skills Training Team and other Departments. All students are required to attend a 2-day Statistical and Experimental Design course at NDORMS and run by the IT department (information will be provided once accepted to the programme).

How to Apply

It is recommended that, in the first instance, you contact the relevant supervisor(s) and the Graduate Studies Office (graduate.studies@ndorms.ox.ac.uk) who will be able to advise you of the essential requirements. Interested applicants should have, or expect to obtain, a first or upper second-class BSc degree or equivalent in a relevant subject and will also need to provide evidence of English language competence (where applicable).

The application guide and form is found online and the DPhil will commence in October 2024.

Applications should be made to one of the following programmes using the specified course code:

D.Phil in Musculoskeletal Sciences (course code: RD_ML2)

D.Phil in Molecular and Cellular Medicine (course code: RD_MP1)

For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford.

References

1.         Ng M, B.R., Gacaferi H, Davidson S, Machado CC, Reekie I, Attar M, Windell D, Kurowska-Stolarska M, MacDonald L, Alivernini S, Garvilles M, Jansen, Bhalla A, Lee A, K, Charlesworth J, Chowdhury R, Klenerman P, Powell K, Hackstein CP, ICECAP study group, Furniss D, Rees J, Gilroy D, Coles M, Carr AJ, Sansom S, Buckley CD, Dakin SG. Primed to resolve: A single cell atlas of the shoulder capsule reveals a cellular basis for resolving inflammatory fibrosis. https://biorxiv.org/cgi/content/short/2023.01.16.522218v1 (2023).

2.         Wynn, T.A. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol 4, 583-594 (2004) DOI: 10.1038/nri1412