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Interdisciplinary investigation of a large effect of sulfasalazine on HbA1c


School of Medicine

, Prof E Pearson Saturday, October 31, 2020 Self-Funded PhD Students Only

About the Project

The anti-inflammatory drug sulfasalazine, which is used in rheumatoid arthritis and inflammatory bowel disease, was reported earlier to suppress HbA1c in a small cohort of patients [1]. In preliminary studies, we have replicated this earlier finding in a much larger dataset of Tayside/Fife patients. This studentship will investigate this effect further, as it may be due either to anti-hyperglycaemic effects possibly suitable for drug repurposing, or alternatively confounding haematological effects. The interdisciplinary nature of the project will afford the student an outstanding opportunity to make high-impact findings relevant to clinical practice, through cross-validation of clinical and cell/molecular insights. To follow up the preliminary data, the student will use state-of-the-art national data hosted by the Scottish Diabetes Research Network epidemiology group. The additional power afforded by this database will be exploited to investigate the clinical impact of sulfasalazine on diabetes phenotypes in patients treated with these drugs. The study will include: replication of existing findings on HbA1c; haematological effects; effects on inflammatory markers (for example C-reactive protein) as well as changes in prescription of oral anti-hyperglycaemic medications or insulin. This element will comprise one third of the studentship. The remainder will be an appraisal of acute effects of sulfasalazine on diabetic and haematological responses, mainly using cell models. This will include the effect of the drug on haemolysis, inflammatory and metabolic signalling, insulin sensitivity, glucose uptake, hepatic glucose production and insulin secretion. In addition, investigation of analogues of the drug will enable the pharmacophore of any effects to be established, as sulfasalazine consists of fused 5-aminosalicyclic acid and sulfapyridine moieties, either or both of which could in principle contribute towards the effects. For the database element, the student will receive training from members of Prof Pearson’s team to extract the data and for the experimental studies they will be supervised by Dr Rena. All methodologies are established either by the supervisors or available through established collaborations [2, 3].

For informal enquiries about the project, contact Dr Graham Rena ()
For general enquiries about the University of Dundee, contact


QUALIFICATIONS
Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK in a relevant discipline.

English language requirement: IELTS (Academic) score must be at least 6.5 (with not less than 5.5 in each of the four components). Other, equivalent qualifications will be accepted. Full details of the University’s English language requirements are available online: http://www.dundee.ac.uk/guides/english-language-requirements.


APPLICATION PROCESS

Step 1: Email Dr Graham Rena () to (1) send a copy of your CV and (2) discuss your potential application and any practicalities (e.g. suitable start date).

Step 2: After discussion with Dr Rena, formal applications can be made via UCAS Postgraduate. When applying, please follow the instructions below:

Apply for the Doctor of Philosophy (PhD) degree in Medicine: https://digital.ucas.com/coursedisplay/courses/87c1cea2-d3ca-455b-a159-9c89bb825b0d. Select the start date and study mode (full-time/part-time) agreed with the lead supervisor.

In the ‘provider questions’ section of the application form:
- Write the project title and ‘FindAPhD.com’ in the ‘if your application is in response to an advertisement’ box;
- Write the lead supervisor’s name and give brief details of your previous contact with them in the ‘previous contact with the University of Dundee’ box.

In the ‘personal statement’ section of the application form, outline your suitability for the project selected.

Funding Notes

There is no funding attached to this project. The successful applicant will be expected to provide the funding for tuition fees and living expenses, via external sponsorship or self-funding.

References

1. Haas, R.M., P. Li, and J.W. Chu, Diabetes Care, 2005. 28: p. 2238.
2. Zhou, K., et al., Nat Genet, 2016. 48: p. 1055-9.
3. Cameron, A.R., et al., Circ. Res., 2016. 119: p. 652-665.

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