Project description

Dupuytren’s disease bends the fingers irreversibly into the palm, threatening employment, selfcare and independence. Despite its prevalence, Surgery temporarily straightens the fingers but does not treat the underlying biology; recurrence is common and repeat operations carry escalating risks to hand function. With genetic risk variants now linked to the disorder, the race is on to understand how these DNA changes affect disease progression and post-operative recurrence risk.

This PhD project uses CRISPR/Cas9 to examine risk variants in patient-derived cells and measure how variants alter force generation, myofibroblast transition and extracellular matrix deposition to contract the fingers. These quantitative, single cell readouts promise to reveal the contributions of these variants to disease progression and severity enabling patients and surgeons to make better informed decisions about the timing of surgical intervention for disease management and reveal molecular switches that could be targeted by anti-fibrotic drugs.

You will master • genome editing, • human iPSC culture and directed differentiation, • live cell biomechanical imaging, and • multiomics analysis skills that are equally prized in academia, biotech and the regenerative medicine sector. By integrating benchtop discoveries with a growing clinical/genetic registry of real patients, your findings can feed directly into precision surgery algorithms and clinical trials. Few PhD projects offer such a clear line of sight from variant to mechanism to clinical translation.

Located on the thriving Norwich Research Park, you will join the teams of Dr Rose Davidson (UEA) and Dr James Smith (UEA) with frontline insights from Miss Mira Pecheva (NHS Orthopaedic Hand Surgeon) offering a rare blend of cell biology, stem cell engineering, biophysics and clinical orthopaedics. You will be based in the Norwich Medical School and Metabolic Health Department, and you can expect strong mentoring culture and career development support.

Entry requirements

The minimum entry requirement is 2:1 in Biological Sciences, Biomedical Science, Biomedicine or similar. Experience with iPSC culture, microscopy, biophysics research is desirable.

Funding

This PhD opportunity offers funding for three years and comprises of tuition fees at Home fee rate, an annual stipend for maintenance starting at £21,611 in the first academic year, and £1,000 per annum to support research training.

References

i) Pecheva M, Warren D, Chojnowski A, Clark I, Davidson R. The abnormal mechanotransduction response of Dupuytren’s fibroblasts from patients with the disease-associated MMP14 Single Nucleotide Polymorphism. International Conference on Dupuytren Disease and Related Diseases. May 2025 (meeting abstract) https://dupuytrensymposium.org/scientific-program/

ii) Jupp, O., et al., Biomarkers of postsurgical outcome in Dupuytren disease, in Dupuytren Disease and Related Diseases - The Cutting Edge, D.J. Werker P, Eaton C, Reichert B, Wach W, Editor. 2016.

iii) Wilkinson, J.M., et al., MMP-14 and MMP-2 are key metalloproteases in Dupuytren's disease fibroblast mediated contraction. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2012. 1822(6): p. 897-905.

iv) Johnston, P., et al., Metalloproteinase gene expression correlates with clinical outcome in Dupuytren's disease. The Journal of hand surgery, 2008. 33(7): p. 1160-1167.

v) Johnston, P., et al., A complete expression profile of matrix-degrading metalloproteinases in Dupuytren’s disease. The Journal of hand surgery, 2007. 32(3): p. 343-351

Dupuytren’s Disease in a Dish: A path to improving clinical management of a debilitating hand disease (DAVIDSONR_U26MEDAA)

Welcome to Norwich

Project description

Entry requirements

Funding

References