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Does Histone Deacetalyse Inhibition Reduce Atherosclerosis and Stroke Risk (PhD only) 


Department of Clinical Neurosciences

Prof H Markus Thursday, December 03, 2020 Competition Funded PhD Project (Students Worldwide)

About the Project

The Cambridge Stroke Group led the identification of the HDAC9 (histone deacetalyse 9) gene as a risk factor for stroke.(Bellenguez et al) The association is specific for large artery stroke due to atherosclerosis. (Markus et al) Further studies have shown increased expression of HDAC9 in the carotid artery plaque, and that reducing HDAC9 expression reduces stroke risk in animal models. Sodium valproate, which is a widely used antiepileptic, is an HDAC inhibitor.(Brookes et al) In large epidemiological datasets we have shown that sodium valproate is associated with reduced stroke risk, compared with other antiepileptics. We are now investigating, in a phase 2 randomised controlled trial design, whether sodium valproate reduces cerebral atherosclerosis via HDAC inhibition.

The project will involve studying the effect of sodium valproate on imaging markers of atherosclerosis including both structural markers (CT/MRI) to look at the volume and type of the atherosclerotic plaque, and positron emission tomographic (PET) markers to look at plaque activation/inflammation. The study would involve patient contact with recruiting and scanning patients. The student would gain experience in clinical research and clinical trial methodology, as well as both performing and analysing brain imaging.



Funding Notes

Funding deadline is 3rd December 2020 for start in October 2021. When applying indicate on the application the funding options (GATES USA *deadline 14/10/20*, Gates Cambridge or other Cambridge Funders). Home/EU and International applications are all considered for funding.

References

Bellenguez, C. et al. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat.Genet. 44, 328–33 (2012).
Markus, H. S. et al. Evidence HDAC9 genetic variant associated with ischemic stroke increases risk via promoting carotid atherosclerosis. Stroke. 44, 1220–5 (2013).
Brookes, R. L. et al. Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack. Stroke 49, 54–61 (2018)



Applicants can only be considered if they apply via the applicant portal which can be found at this link; https://www.graduate.study.cam.ac.uk/ please do not send in an enquiry and CV as this will not be considered an application.

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