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Can orally delivered gas nanobubbles relieve joint hypoxia #NDORMS 2020/10


About This PhD Project

Project Description

Joint hypoxia is a feature of many rheumatological conditions and results in upregulation of HIF (hypoxia-inducible factors). HIFs are thought to mediate a number of maladaptive features of joint disease, but to date attempts to develop small molecule inhibitors of HIF have not been successful. Innovative technology developed in Prof Eleanor Stride’s lab has led to the development of gas nanobubbles (air or oxygen) in the form of a drink. The core of this DPhil project is an experimental medicine study to establish whether orally delivered gas nanobubbles can relieve joint hypoxia and thus may deliver novel benefits in joint disease. The laboratory component of this project will be to explore the mechanistic basis of HIF-mediated pathology in joint disease.

Essential and Desired Qualifications/Experience


Essential Criteria:
• Hold or be about to obtain a medical degree
• Demonstrable interest in translational medicine and rheumatology

Additional Qualifications:
• MRCP or equivalent would be preferred
• A good team player as well as an ability to work independently.
• Experience of clinical research would be an advantage

Details of the Research Group


The DPhil will be jointly supervised by Prof Eleanor Stride (Professor of Biomedical Engineering) and Prof Duncan Richards (Climax Professor of Clinical Therapeutics) at the Oxford Centre for Clinical Therapeutics (NDORMS) Botnar Research Centre, Oxford.
This DPhil is being funded by the John Climax donation.

Professor Eleanor Stride
https://www.ndorms.ox.ac.uk/team/eleanor-stride
Has published extensively in the field of Biomaterials and engineering and engineers drug delivery systems using carefully designed microbubbles and studies how they can be used in diagnostics.

Professor Duncan Richards
https://www.ndorms.ox.ac.uk/team/duncan-richards
Has published extensively in the field of Clinical Pharmacology and Experimental Medicine. Professor Richards is establishing a new Centre for Clinical Therapeutics and is based at the Botnar Research Centre and St. Hilda’s College, Oxford. Professor Richards aims to work with a diverse range of Oxford biomedical researchers and with the pharmaceutical, biotechnology and diagnostics industries in order to drive new treatments through decision making in early phase clinical trials.

Dr Laura Coates
https://www.ndorms.ox.ac.uk/team/laura-coates
Dr Coates is an NIHR Clinician Scientist and Senior Clinical Research Fellow. She has pulished extensively on therapeutic implementation in psoriatic arthropathy and has a particular interest in means to personalize treatment pathways.

Associate Professor Philippa Hulley
https://www.ndorms.ox.ac.uk/team/philippa-hulley
Has published extensively in the field of body and molecular medicine. Professor Hulley is a University Lecturer with NDORMS and also teaches undergraduate medical students at St. Hilda’s College, Oxford. She tutors preclinical medics in the organisation of the body and molecular medicine and tutors in Biomedical Sciences at St. Hilda’s college Oxford.

Training


Training will be provided in the clinical procedures required to conduct the clinical study and how to plan and conduct compliant clinical studies.

In addition a core curriculum of lectures organized departmentally will be taken in the first term to provide a solid foundation in a broad range of subjects related to doctoral study.

How to Apply


The department accepts applications throughout the year but it is recommended that, in the first instance, you contact the relevant supervisors or the Graduate Studies Officer, Sam Burnell (), 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, and will also need to provide evidence of English language competence. The application guide and form are found online and the DPhil will commence in October 2020.

For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford and/or contact Prof Duncan Richards ()

References

Owen J, McEwan C, Nesbitt H, Bovornchutichai P, Averre R, Borden M, McHale AP, Callan JF, Stride E. Reducing tumour hypoxia via oral administration of oxygen nanobubbles. PloS one. 2016 Dec 30;11(12):e0168088. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168088

Hulley PA, Bishop T, Vernet A, Schneider JE, Edwards JR, Athanasou NA, Knowles HJ. Hypoxia‐inducible factor 1‐alpha does not regulate osteoclastogenesis but enhances bone resorption activity via prolyl‐4‐hydroxylase 2. The Journal of pathology. 2017 Jul;242(3):322-33.

https://onlinelibrary.wiley.com/doi/full/10.1002/path.4906

Hua S, Dias TH. Hypoxia-inducible factor (HIF) as a target for novel therapies in rheumatoid arthritis. Frontiers in pharmacology. 2016 Jun 27;7:184.

https://www.frontiersin.org/articles/10.3389/fphar.2016.00184/full

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