Dr Anvesha Singh and Dr Marcin Wozniak
This studentship is funded by the Leicester Precision Medicine Institute (LPMI) and is placed within the supportive and nurturing environment provided by the Leicester Institute of Precision Medicine, the Leicester Biomedical Research Centre and the Leicester Centre for Cancer Research. You will receive financial backing and the support of an inclusive and collaborative research culture - enabling you to realise your potential.
Narrowing of the aortic valve or ‘aortic stenosis’, is the commonest type of valve disease requiring surgery in the western world. With an ageing population, its incidence is increasing. The only available treatment is aortic valve replacement (AVR, usually open heart surgery), which is recommended once symptoms occur. Studies using cardiac MRI scans have shown that changes such as scarring (late gadolinium enhancement/LGE) occur within the heart muscle at a much earlier stage, some of which does not reverse even AVR, and remains a predictor of mortality even after surgery. This suggests that the current timing of AVR may be too late for some.
Identification of blood and imaging biomarkers that can identify those at the highest risk of developing scarring and therefore benefit from earlier intervention, is an unmet research need. We have plasma stored from 174 patients who had asymptomatic moderate to severe AS, and underwent detailed assessment, including cardiac MRI. Forty-three of them had a repeat MRI/plasma collection at 12 months, whilst asymptomatic.
This PhD will focus on exploring the role of microRNAs (small, non-coding RNAs that inhibit translation of messenger RNA into proteins). They are detectable in blood, allowing their potential as biomarkers. Previous studies have shown certain miRs to be linked to changes seen in AS, such as muscle thickening (hypertrophy) and scarring (fibrosis). The student will conduct a systematic review on the role of miRs in AS, followed by detailed review of the published transcriptomics and proteomics datasets to identify important signalling pathways associated with fibrosis. Finally, they will perform miR sequencing using next-generation sequencing on the 43 patients with paired MRI, to identify important miRs associated with fibrosis progression. These will be validated in the full cohort and linked to MRI markers of remodelling, as well as long-term clinical outcomes in this cohort.