Developing a pluripotent stem cell therapy for Achalasia

A 3-year PhD Studentship in Regenerative Medicine funded by the The Mosawi Foundation is available within the UCL Great Ormond Street Institute of Child Health. The studentship will commence from 1st October 2025 onwards (start dates may be negotiable), under the supervision of Dr. Conor Mccann.

Background

The treatment of Oesophageal Achalasia remains a significant clinical challenge. The continued lack of a curative treatment and significant morbidity of long term interventional therapies mean that better understanding of disease aetiology and alternative therapeutic options are vital. Potential replacement of lost neurons using stem cell transplantation is an attractive therapy for such life limiting motility disorders. Recent investigations from the McCann group have highlighted the potential of enteric nervous system (ENS) progenitors derived from human pluripotent stem cells (hPSC) as a source of donor cells which may rescue function in the intestine.

Hypothesis/Aims

We hypothesise that ENS progenitor transplantation may alleviate symptoms associated with loss of neurons in Achalasia. The aims of this project are to assess the ability of hPSC-derived ENS progenitors to rescue an Achalasia phenotype in a mouse model of disease and investigate the aetiology of Achalasia in a defined human cohort.

Research and policy outputs

The outlined aims will lead to high impact publications on:

  • Possible aetiology and progression of Achalasia providing key clinical data which may impact upon current clinical guidance for the treatment of Achalasia.
  • Provide pivotal preclinical data on the efficacy of ENS progenitor translation to the oesophagus.

References

  • Rivera LR, Poole DP, Thacker M, Furness JB. The involvement of nitric oxide synthase neurons in enteric neuropathies. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society 2011;23:980-8.
  • Sivarao DV, Mashimo HL, Thatte HS, Goyal RK. Lower esophageal sphincter is achalasic in nNOS(-/-) and hypotensive in W/W(v) mutant mice. Gastroenterology 2001;121:34-42.
  • Sarni SS, Haboubi HN, Ang Y, Boger P, Bhandari P, de Caestecker J, Griffiths H, Haidry R, Laasch HU, Patel P, Paterson S, Ragunath K, Watson P, Siersema PD, Attwood SE. UK guidelines on oesophageal dilatation in clinical practice. Gut 2018;67:1000-10
  • Frith TJR, Gogolou A, Hackland JOS, Hewitt ZA, Moore HD, Barbaric I, Thapar N, Burns AJ, Andrews PW, Tsakiridis A, Mccann CJ. Retinoic Acid Accelerates the Specification of Enteric Neural Progenitors from In-Vitro-Derived Neural Crest. Stem Cell Reports 2020;15:557-565.
  • Jevans B, Cooper F, Fatieieva Y, Gogolou A, Kang YN, Restuadi R, Moulding D, Vanden Berghe P, Adameyko I, Thapar N, Andrews PW, De Coppi P, Tsakiridis A, Mccann CJ. Human enteric nervous system progenitor transplantation improves functional responses in Hirschsprung disease patient-derived tissue. Gut 2024;73:1441-1453.

About you

Applicants should have, or expect to receive an upper second-class Bachelor's degree and/or a Master's degree (or equivalent work experience) in a relevant discipline or an overseas qualification of an equivalent standard.

What we offer

This studentship provides a starting stipend of £22,780 per annum and covers the cost of tuition fees based on either the UK or international rate (whichever is applicable).

How to Apply 

Please do not click the 'Apply Now' button next to the advert.

Enquiries regarding the post can be made to Dr Conor Mccann (conor.mccann@ucl.ac.uk)

To apply, please send a current CV including the contact details of two professional referees as well as a 1 sided A4 cover letter to Dr. Conor Mccann (conor.mccann@ucl.ac.uk).

Closing date for applications: Friday 18th April 2025

Interview date: Week commencing 5th May 2025

Applications that are submitted without following the correct application process will not be considered. The successful applicant will then be required to apply to and register on the Child Health research degree to take up the studentship

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