The Lewis Spitz Surgeon Scientist PhD programme
This page contains information about the Lewis Spitz Surgeon Scientist PhD programme. Please note that the programme is currently closed. Future opportunities will be announced widely.
About the Lewis Spitz Surgeon Scientist PhD programme
The Lewis Spitz Surgeon Scientist PhD programme was established in 2017 and supported by the Great Ormond Street Hospital (GOSH) Charity and National Institute for Health and Care Research (NIHR) GOSH Biomedical Research Centre (BRC) to develop future surgeon scientist leaders with excellence in translational research.
The programme is driven by the need to increase capacity through training in the scientific basis of paediatric surgery, with a focus on treating children who suffer from congenital malformations, cancers and other conditions requiring surgery. The key aim of the scheme is to develop future surgeon scientist leaders with excellence in translational research.
This scheme provides a full-time research opportunity for trainee surgeons to complete a UCL PhD over 3 years, covering the salary, tuition fees, consumables and travel. The programme is open to all surgical trainees (up to but excluding consultant level) who have demonstrated a commitment to a career in surgical treatment of children. All sub-specialties within children’s surgery are invited to apply, including neurosurgery, orthopaedics, craniofacial, cardiothoracic and general paediatric surgery. Each successful candidate is supervised by an ICH research leader and a practising GOSH consultant surgeon.
Lewis Spitz Surgeon Scientist cohort
The Lewis Spitz Surgeon Scientists are outstanding surgeons and researchers. To date, the programme has supported eight fellows with a further two offered a place on the programme in 2024/25 academic year. You can learn more about the fellows and their research using the drop-down links below.
Sebastian Toescu (2017-2021)

Sebastian attended medical school at the University of Bristol and after completing his Academic Foundation Programme at the Royal Free Hospital and a year of Core Surgical Training at King’s College Hospital, entered the Neurosurgery training programme in London in 2015. He was appointed as the first Lewis Spitz Fellow in 2017, and took time out of programme to complete his PhD at GOSH and UCL-GOS Institute of Child Health. He was supervised by Professor Chris Clark and Mr Kristian Aquilina, and spent a portion of his research at Stanford University, California. He is now completing his training in neurosurgery. Sebastian was appointed as the first SBNS Caribbean Training Fellow in 2024, travelling to Kingston, Jamaica, where he will undertake neurosurgical training in trauma, paediatrics and general neurosurgery. His career goal is to become a consultant neurosurgeon specialising in paediatric neuro-oncology with commitments to clinical, academic and teaching activity.
Motivation for wanting to be a surgeon scientist.
In order to keep the field of paediatric surgery moving forward. If we don’t ask questions of what we are doing then in twenty years’ time we will look around and realise we are doing the same operations, in the same way, on the same patients, as we always were. It’s about finding out what those questions are, and working on strategies to answer them in a way that translates to better care for patients.
Thoughts on the fellowship in terms of the opportunity it offered to pursue being a surgeon-scientist, which is otherwise a rare opportunity.
The Lewis Spitz fellowship is an unparalleled opportunity for aspiring paediatric surgeons. Fundamentally, the fellowship afforded me time away from the clinical coalface of training rotations, giving me the headspace to think more deeply about the questions I had proposed in my research; and the time to learn high-level image processing techniques required to demonstrate results. I felt really well supported both academically - as I had joined a thriving lab where I was able to learn from others; and clinically - as I rejoined the world-class neurosurgery department at GOSH for patient recruitment and on-call work.
Why do you think it is an important role in the landscape of paediatric healthcare?
Patient numbers are often smaller in paediatric conditions than they are in adult medicine – particularly for things like brain tumours – and this poses a research challenge. By developing a network of paediatric surgeon scientists, we can leverage collaborative studies to provide more definitive answers to difficult research questions. Regular interactions with these networks of peers can help drive the conversations forward into new, exciting directions.
About the PhD project
Supervisors: Professor Christopher A Clark and Mr Kristian Aquilina
Surgical Speciality: Neurosurgery
PhD project abstract:
Brain tumours in children frequently occur in the posterior fossa. Most undergo surgical resection, after which up to 25% develop cerebellar mutism syndrome (CMS), characterised by mutism, emotional lability and cerebellar motor signs; these typically improve over several months. This thesis examines the application of diffusion (dMRI) and arterial spin labelling (ASL) perfusion MRI in
children with posterior fossa tumours.
dMRI enables non-invasive in vivo investigation of brain microstructure and connectivity by a computational process known as tractography. The results of a unique survey of British neurosurgeons’ attitudes towards tractography are presented, demonstrating its widespread adoption and numerous limitations. State-of-the-art modelling of dMRI data combined with tractography is used to probe the anatomy of cerebellofrontal tracts in healthy children, revealing the first evidence of a topographic organization of projections to the frontal cortex at the superior cerebellar peduncle. Retrospective review of a large institutional series shows that CMS remains the most common complication of posterior fossa tumour resection, and that surgical approach does not influence surgical morbidity in this cohort.
A prospective case-control study of children with posterior fossa tumours treated at Great Ormond Street Hospital is reported, in which children underwent longitudinal MR imaging at three timepoints. A region-of-interest based approach did not reveal any differences in dMRI metrics with respect to CMS status. However, the candidate also conducted an analysis of a separate retrospective cohort of medulloblastoma patients at Stanford University using an automated tractography pipeline. This demonstrated, in unprecedented spatiotemporal detail, a fine-grained evolution of changes in cerebellar white matter tracts in children with CMS. ASL studies in the prospective cohort showed that following tumour resection, increases in cortical cerebral blood flow were seen alongside reductions in blood arrival time, and these effects were modulated by clinical features of hydrocephalus and CMS.
The results contained in this thesis are discussed in the context of the current understanding of CMS, and the novel anatomical insights presented provide a foundation for future research into the condition.
Impact/outcomes from the PhD; Patient benefit (including anticipated)
- Development and validation of a pre-operative risk calculator for CMS which is used in consent discussions with families
- I am a board member of the worldwide Posterior Fossa Society which is dramatically increasing the global awareness of this condition and engaging families and therapists in order to generate small but significant improvements in the care of affected children
You can read more about Sebastian's research on UCL Profiles
Aswin Chari (2019-2022)

Aswin is a North Thames neurosurgical trainee and aspiring academic paediatric neurosurgeon. Following completion of his Lewis-Spitz Surgeon-Scientist Fellowship, he has obtained an NIHR Academic Clinical Lectureship, which has allowed him to continue his research in the fields of paediatric epilepsy and paediatric epilepsy surgery at GOSH & UCL GOS Institute of Child Health.
Motivation for wanting to be a surgeon scientist:
As an aspiring paediatric neurosurgeon, I am committed to improving the lives of children with neurosurgical conditions and specifically epilepsy. The motivation to be involved in research is wanting to contribute to improving treatments for future children, making them more accessible, effective and safe.
Thoughts on the fellowship in terms of the opportunity it offered to pursue being a surgeon-scientist, which is otherwise a rare opportunity:
The Lewis-Spitz Scientist Fellowship offered me an unparalleled opportunity to delve into the world of paediatric epilepsy surgery at a leading centre in the UK, Europe and worldwide. At GOSH and UCL-GOS Institute of Child Health, I had exposure to clinical and academic expertise in a wide range of fields and was able to regularly speak to and conduct projects with people who are looking to push boundaries to improve our knowledge and treatments for epilepsy.
Why do you think it is an important role in the landscape of paediatric healthcare?
Surgeon-scientists are in a unique position to be able to do research to advance surgical treatments. They are able to take problems from the clinical setting and attempt to solve them in the lab whilst also being able to translate solutions from the lab into clinical practice to improve outcomes. In the field of epilepsy, I see it as my role in the future to help identify and translate new solutions and treatments to the operating theatre and beyond to help make future surgical treatments more accessible, effective and safe.
Future direction and opportunities that the scheme has offered:
The scheme has set me on the path towards becoming an academic paediatric neurosurgeon. Since completing the PhD, I have been awarded an NIHR Academic Clinical Lectureship to continue the line of research, with a main focus on improving the timing of surgical intervention for paediatric epilepsy and assessing the role of the thalamus in children undergoing invasive monitoring at GOSH.
About the PhD project
Title: Interictal network dynamics in paediatric epilepsy surgery
Supervisors: Rod Scott, Martin Tisdall, Richard Rosch, Rachel Thornton
Surgical Speciality: Neurosurgery
Abstract:
Epilepsy is an archetypal brain network disorder. Despite two decades of research elucidating network mechanisms of disease and correlating these with outcomes, the clinical management of children with epilepsy does not readily integrate network concepts. For example, network measures are not used in presurgical evaluation to guide decision making or surgical management plans. The aim of this thesis was to investigate novel network frameworks from the perspective of a clinician, with the explicit aim of finding measures that may be clinically useful and translatable to directly benefit patient care. We examined networks at three different scales, namely macro (whole brain diffusion MRI), meso (subnetworks from SEEG recordings) and micro (single unit networks) scales, consistently finding network abnormalities in children being evaluated for or undergoing epilepsy surgery. This work also provides a path to clinical translation, using frameworks such as IDEAL to robustly assess the impact of these new technologies on management and outcomes. The thesis sets up a platform from which promising computational technology, that utilises brain network analyses, can be readily translated to benefit patient care.
Impact/outcomes from the PhD; Patient benefit (including anticipated):
Novel method of structural brain network analysis using diffusion MRI in paediatric epilepsy, first in human translation of machine learning tool to help localise seizures in children with focal epilepsy
You can read more on Aswin's research on UCL Profiles
Natalie Durkin (2019-2025)
Natalie is a paediatric surgical trainee in the South East of England. After undertaking medical school and foundation training in Birmingham, she undertook 6 years of surgical training in London before applying to the Lewis Spitz Surgical Scientist Fellowship in 2019. Her work focused on demonstrating the safety and function of a laboratory-generated (‘tissue-engineered’) oesophagus as an alternative for patients born with long-gap oesophageal atresia at UCL-GOS Institute of Child Health under the supervision of Prof Paolo De Coppi, Prof Simon Eaton and Prof Paola Bonfanti. During her PhD, she fostered a close collaboration with the Tracheo-Oesophageal Fistula Support (TOFS) patient charity, undertaking research in areas identified as important to them as a patient body. After the successful implantation of tissue-engineered oesophagus in a porcine model, she returned to surgical training in February 2024, where she continues to drive this work towards translation. She aspires to be a thoracic and upper gastrointestinal surgeon scientist with a specialist interest in oesophageal atresia.
Motivation for wanting to be a surgeon scientist
During my training as a paediatric surgeon, I have come across several children with congenital problems; fortunately, most of which can be surgically corrected. For some children, however, the optimal solution has not yet been found, and despite surgical correction, many experience lifelong difficulties with feeding and gut function. Being at the interface of clinical prac and research, surgeon scientists are uniquely placed to understand the challenges faced by surgical patients and investigate novel ways in which these could be better treated, ultimately aiming to improve patient outcomes. Tissue engineering specifically offers the very real possibility to provide a curative therapeutic solution for children born with missing or damaged organs, where very little change to surgical management has occurred for the last 50 years. The opportunity to be at the forefront of this step change in surgical approach and to understand how it may benefit our patients is hugely exciting.
Thoughts on the fellowship in terms of the opportunity it offered to pursue being a surgeon-scientist, which is otherwise a rare opportunity.
The Lewis Spitz GOSHCC surgical scientist fellowship has been instrumental in changing the course of my career. Having previously had an interest in clinical academics with little exposure to basic science, I was immediately immersed within a community of dedicated and knowledgeable multidisciplinary researchers including cell biologists, biomechanical engineers and bioinformaticians. They provided me with a rigorous basic science training and encouraged me to view problems from multiple perspectives. I gained an in depth theoretical and practical understanding of the techniques in our armoury to investigate the developmental biology underpinning congenital paediatric surgical conditions and novel treatment options, within a world class institution with cutting edge facilities. The fellowship gave me the opportunity to collaborate with world leaders in the field of oesophageal atresia and, most importantly, the patient charity TOFS, who have helped direct my resources and energies to the work that matters most to patients, including quality of life and transition of care.
Why do you think it is an important role in the landscape of paediatric healthcare?
Although individually rare, congenital and neonatal diseases such as oesophageal atresia, short gut syndrome and Hirschsprung’s disease are common. However, treatment options for many of these conditions are limited, resulting in ongoing compromise of gut function even after surgical correction. Paediatric surgical conditions therefore often have a significant and long-term impact on the physical and psycho-social wellbeing of both the child and their wider family network into adulthood. This often requires lifelong surveillance and multiple interventions and therefore also has a significant impact on resource utilisation within the NHS. As such, we must continue to strive for novel solutions which may improve long-term outcomes for our patients. The combination of surgical and academic training means paediatric surgical scientists uniquely placed to understand the nuances of the rare and complex diseases we treat, identify outcomes of importance to patients and their families, explore innovative surgical solutions, and identify and overcome challenges for future clinical translation.
Future direction and opportunities that the scheme has offered:
This PhD fellowship has been instrumental in setting me on the path towards becoming an academic surgeon, with the aim to apply for a Academic Clinical Lectureship position in the near future to continue to drive this work towards translation. We have successfully applied for funding to begin the rigorous process of adaptation of tissue engineered oesophagus for human use, including the establishment of formal quality control processes in collaboration with the Medicines and Healthcare products Regulatory Agency (MHRA). We have also applied for funding to develop a patient focus group to help shape a future first-in-human clinical trial.
About the PhD project
Research project title: Oesophagus tissue engineering in large animals as a preclinical model for the treatment of oesophageal atresia
Supervisors: Paolo De Coppi, Simon Eaton, Paola Bonfanti
Surgical Speciality: Paediatric Surgery
PhD project abstract:
Oesophageal atresia (OA) is a spectrum of rare congenital malformations where faulty embryonic separation of the oesophagus and trachea results in a disruption in oesophageal continuity and an abnormal connection between the two. In 10% of patients, with a subtype known as long-gap, primary anastomosis is often not feasible due to a large tissue deficit, resulting in the requirement for an oesophageal substitute. Current options for oesophageal replacement are suboptimal; surgical creation of gastric, jejunal or colonic substitutes result in loss of function of that organ and all three techniques are associated with significant long-term complications and morbidity.
Tissue engineering offers huge potential as a novel strategy to treat complex congenital and acquired conditions of the oesophagus where standard therapy has failed or current options for organ replacement fall short. In 2018, Urbani et al published the proof-of-principle of a tissue engineered oesophageal construct in vitro by seeding human mesoangioblasts, mouse fibroblasts and rat epithelial cells on a decellularised rat oesophageal scaffold. The scope of this work focuses on the challenges addressed in order to upscale this model in vitro prior to eventual delivery of this model in vivo by optimising decellularisation of porcine oesophagus, isolating and characterising porcine mesoangioblasts and fibroblasts from skeletal muscle biopsies and investigating the effect of bioactive molecules and co-culture on cell migration in 2D and 3D prior to thoracic transplantation in vivo in mini pigs to assess the safety, feasibility and efficacy of this approach as a preclinical model for the treatment of long-gap oesophageal atresia.
You can read more on Natalie's research here
James Wawrzynski (2020-2024)

James studied medicine at Cambridge University, graduating in 2013. He also undertook an intercalated degree in physiology, development and neuroscience, graduating with 1st class honours. He then went on to work as a foundation year doctor in a range of medical and surgical specialties within the East of England deanery. In 2015 he was selected for the ophthalmic surgical training programme in the North London deanery and has since subspecialised in vitreoretinal surgery. He is currently a vitreoretinal fellow at Moorfields Eye Hospital. He has been actively involved in research throughout his medical career initially focusing on medial and surgical education and later on retinal vascular disease. He recently completed a 3 year PhD placement at the UCL Institute of Child Health, Great Ormond Steet hospital and Moorfields Eye Hospital working on a gene therapy for Norrie disease, Familial Exudative Vitreoretinopathy, Coats disease and Retinopathy of Prematurity. During this time he also worked on a novel application of an existing therapeutic agent in the treatment of Batten disease associated retinal dystrophy.
Motivation for wanting to be a surgeon scientist.
Nowadays medicine is highly protocol driven. The days of doctors bringing in their own original thought to the treatment of most conditions are, fortunately, behind us. This change has come about for very good reason. Medicine is now increasingly evidence based, enabling decisions to be made based on the results of treating thousands of patients rather than the experience of individual clinicians. This has led to more effective and increasingly cost-efficient medicine being practiced.
However, when it comes to the development of new treatments for currently untreatable conditions the doctor once again has to rely on a solid clinical and scientific grounding and is able to develop and contribute their own ideas and solutions to problems. For me this is one of the most exciting aspects of medicine. Ultimately these treatments may be incorporated into standard protocols and become a routine part of clinical practice. Therefore involvement in medical research nowadays is potentially highly impactful and has the potential to help many more patients than an individual doctor could on their own.
I have chosen a surgical specialty as each and every case is different and, like medical research, involves problem solving. I also feel that surgical research lags behind medical research as it is much more difficult to standardise treatment. Leading on surgical research therefore had the potential to be both highly challenging and impactful.
I also find that patients and relatives of patients with rare disease that may be difficult to treat are often highly interested in their condition and motivated to help find new treatments, even if only for the next generation. Working together with such patients is a great privilege.
Thoughts on the fellowship in terms of the opportunity it offered to pursue being a surgeon-scientist, which is otherwise a rare opportunity.
The Lewis Spitz Surgeon Scientist research fellowship has provided me with quite a unique opportunity to pursue both lab based and clinical research in tandem. Throughout my fellowship I was able to learn about the presentation and treatment of patients with the conditions that I was investigating at the same time as developing a molecular treatment for their condition. Seeing patients in clinic influenced the direction of my lab based work by understanding with aspects of the condition trouble patients the most, and the least.
I have published my work in high impact scientific journals and have recently been selected for the vitreoretinal fellowship at Moorfields Eye Hospital.
I am involved in on-going postdoctoral research related to my PhD work as well as an exciting new project with the same team.
The opportunities afforded to me by completing the Lewis Spitz fellowship have enabled me to develop myself as a surgeon scientist and are likely to make be competitive when applying for further research funding to lead combined academic and clinical work as a consultant ophthalmologist in the future.
Why do you think it is an important role in the landscape of paediatric healthcare?
Paediatric research is challenging due to the young age of the patients involved and the huge diversity of rare conditions that affect children. Many of these conditions still have no effective treatments. Paediatric healthcare therefore requires a substantial number of paediatric surgical scientists working on solving these problems. The Lewis Spitz programme provides a tailor made route for aspiring paediatric surgeons to become paediatric surgical scientists.
Future direction and opportunities that the scheme has offered:
The scheme has enabled me to develop a solid clinical and academic grounding in paediatric vitreoretinal conditions. I am now involved in further research to hopefully take forward NDP gene therapy into clinical trials. In addition, I am involved in several other exciting new projects with the same team that make use of the surgical and academic expertise I have developed during the Lewis Spitz fellowship. At the same time I have taken on a role as vitreoretinal fellow at Moorfields Eye Hospital, which will enable me to sub-specialise in vitreoretinal surgery. Eventually I hope to become a consultant vitreoretinal surgeon scientist leading on the development of novel surgical treatments.
About the PhD project
Research project title: Molecular treatments for paediatric vitreoretinal disease: developing gene therapy for NDP-related retinal disease and delivering enzyme replacement for CLN2 retinopathy
Surgical speciality: Vitreoretinal Surgery
Supervisors: Professor Jane Sowden, Mr Robert Henderson
PhD project abstract:
Inherited vitreoretinal disease is a common cause of childhood visual impairment. With the notable exception of treatment for RPE65, no molecular treatments for these conditions are available. I aimed to develop and test a gene therapy for NDP-related retinal disease and to translate a previously studied enzyme replacement therapy for CLN2 retinopathy from animal studies into a human trial.
Pathogenic variants in NDP (Xp11.3) result in a spectrum of retinal disease from peripheral non-perfusion, to sight threatening exudative/tractional
retinal detachment. In a systematic review of published case reports I found that variants affecting the NDP/FZD4 interaction or the NDP homodimer tend to cause severe disease (historically termed Norrie Disease) whereas variants affecting the NDP/LRP5 interaction tend to cause moderate disease (historically termed FEVR). I also found an association between heterozygous NDP pathogenic variants and Coats disease and between otherwise benign variants in NDP and retinopathy of prematurity.
I developed an AAV gene therapy for NDP retinal disease and tested iterations of the treatment in an Ndp KO mouse model. When administered during retinal vascular development, AAV.NDP rescued vascular architecture and reduced exudation. When administered later, AAV.NDP reduced exudation and pathological neovascularisation but did not ameliorate the vascular architecture.
Pathogenic variants in CLN2 result in dysfunctional TPP-1 lysosomal enzyme. From the age of 2-4 patients develop progressive neurological decline and retinal dystrophy, followed by premature death. Whilst intracerebroventricular enzyme replacement is available to prevent neurological decline, no treatment is available for the retinopathy. I translated experimental results from a canine model into human patients and found that intravitreal replacement of TPP-1 slows CLN2 related retinal degeneration.
In summary, this thesis describes the development of an effective novel gene therapy for NDP retinopathy using a murine model and the translation of an enzyme replacement therapy from a canine model into human patients for the first time.
Impact/outcomes from the PhD; Patient benefit (including anticipated)
My research into Batten disease has resulted in the finding of an effective molecular therapy for the treatment of retinal dystrophy in Batten disease. This has led on to a gene therapy trial to deliver the same treatment without the need for repeated intravitreal injections. The trial is currently taking place at Great Ormond Street Hospital.
My research into NDP related retinopathy has resulted in the development of a novel gene therapy for this condition, which is effective in mice and to a current research project involving patients to determine the best candidates for a future clinical trial.
My research into surgery for ROP/ FEVR has demonstrated that combined biom and endoscopic vitrectomy is a better surgical approach for neonatal tractional retinal detachment related to these conditions than traditional biom-assisted vitrectomy alone.
You can read more about James' research works here
Rory Piper (2021-2024)

I am a Clinical Lecturer in Paediatric Neurosurgery at the UCL Great Ormond Street Institute of Child Health. I completed the Lewis-Spitz Surgeon-Scientist Programme in 2024 with research focusing on ‘network-guided epilepsy surgery for children’, with projects in neuroimaging and deep brain stimulation. I have previously completed the Academic Clinical Fellowship in Neurosurgery at the John Radcliffe Hospital (Oxford) and the Academic Foundation Programme (Cambridge).
Motivation for wanting to be a surgeon scientist.
My ultimate goal is to become an academic paediatric neurosurgeon and to use that role to help children with debilitating neurological conditions. My long-term plan is to develop, build and lead an integrated clinical and academic functional neurosurgery service to help children with drug-resistant neurological conditions, such as epilepsy, dystonia and spasticity.
Thoughts on the fellowship in terms of the opportunity it offered to pursue being a surgeon-scientist, which is otherwise a rare opportunity.
During my PhD I was the trial fellow for the CADET Project, which trained me in skills critical to the design, set-up and delivery of clinical device trials in neurosurgery. This unique experience in paediatric neurosurgical research provided me a springboard of abilities that I can draw upon in the next stage of my career. I received a hands-on experience of device trials which trained me in all of the regulatory components of clinical device trials and an opportunity to gain experience in collaborating with engineering teams and industrial partners.
Why do you think it is an important role in the landscape of paediatric healthcare?
It is imperative that we develop novel surgical therapies so that we can provide the very best outcomes to children with medical disorders. For example, epilepsy is a common condition (affecting ~600,000 in UK) and approximately one third of children with epilepsy will continue to have seizures despite taking anti-seizure medications. For carefully selected children with ‘medication-resistant’ epilepsy, neurosurgery can deliver either seizure freedom or significant seizure frequency reduction – providing a dramatic and life-long benefit to these patients. However, we still have more work to do in this area, and it is crucial that neurosurgeons engage with and lead research in this area to develop new surgical therapies to achieve good outcomes for all children with medication-resistant epilepsy.
Future direction and opportunities that the scheme has offered:
During my PhD at UCL Great Ormond Street Institute of Child Health I was a co-applicant on a successful grant application to the NIHR Inventions 4 Innovation (i4i) Product Development Award (PDA) scheme. This project will fund an exciting novel project focused on refining deep brain stimulation for children with drug-resistant epilepsy. Furthermore, the funding has enabled me to take on a Clinical Lectureship in Paediatric Neurosurgery, which will be a pivotal next step in my academic neurosurgical career.
About the PhD project
Research project title: Network-guided surgery for children with epilepsy
Surgical speciality: Neurosurgery
Supervisors: Mr. Martin Tisdall, Prof. Torsten Baldeweg, Dr. David Carmichael
PhD project abstract:
Epilepsy is a disorder of brain networks. The connectivity of the brain may be analysed by considering the brain as a graph with nodes (brain regions) and edges (a measure of connectivity between nodes). There is a growing body of research to identify critical nodes within dynamic epileptogenic networks with the aim to target therapies that halt the onset and propagation of seizures. This PhD thesis applies a networks approach to epilepsy surgery and focuses on two particular propagation points or nodes (piriform cortex (PC) and thalamus) within epileptogenic networks and reports three studies at different steps of the clinical translational pathway. Study #1 was a retrospective study investigating the association between the extent of resection of the PC and post-operative seizure freedom in children who underwent anterior temporal lobe resection for temporal lobe epilepsy (TLE). This is the first study demonstrating that, in children with TLE and hippocampal atrophy, more extensive temporal PC resection is associated with a greater chance of seizure freedom. Study #2 was a prospective ultra-high-field (7-Tesla) MRI study investigating the functional connectivity of the PC and thalamus in children and adults with TLE. This study did not find functional connectivity differences in either mesial temporal lobe structures or thalamic subregions in the full TLE cohort compared to controls. Reduced functional connectivity of amygdala and increased functional connectivity of ventral -anterior nucleus of the thalamus were found in patients with hippocampal atrophy compared to those without. Study #3 reports on the outcomes for the first participant recruited to the Pilot Study of the Children’s Adaptive Deep brain stimulation for Epilepsy Trial (CADET) , a consecutive series of prospective, multicentre, interventional clinical trials of deep brain stimulation of the centromedian nucleus of the thalamus in treating children with Lennox-Gastaut Syndrome.
Impact/outcomes from the PhD; Patient benefit (including anticipated)
A significant component of my PhD work was the Children’s Adaptive Deep brain stimulation for Epilepsy Trial (CADET) Project – a series of consecutive prospective clinical device trials that investigates the safety, feasibility and effectiveness of a novel cranially-mounted DBS device to treat children with Lennox-Gastaut Syndrome (a severe form of generalised-onset epilepsy). The most significant impact and milestone of my PhD was in achieving the first-in-child and first-in-epilepsy application of this therapy. This CADET programme marks the first intracranial neuromodulation study at GOSH and will provide a platform to translate DBS as an effective and available form of therapy for children with Lennox-Gastaut Syndrome.
Featured on BBC and GOSH websites:
https://www.bbc.co.uk/news/articles/cg33kgd81mvo
https://www.gosh.nhs.uk/news/first-uk-trial-of-deep-brain-stimulation-for-children-with-epilepsy-begins-at-gosh/
You can read more about Rory's research works here
James Arwyn-Jones (2023-2026)

I am an ENT registrar currently taking time out of training to undertake a PhD in Prof. Jane Sowden’s lab, via the Lewis Spitz Surgeon Scientist Fellowship. I graduated from Oxford in 2016 and spent my foundation training years in the Thames Valley region before moving to London. I have an interest in ear surgery, and I am pursuing a career in Otology; to treat patients who require surgical management of their hearing loss and other ear conditions.
Motivation for wanting to be a surgeon scientist.
My professional motivation for wanting to be a surgeon scientist stems from an interest in genetics and genetic hearing loss. I find human genetics fascinating and view the pursuit of understanding and treating genetic diseases as a new frontier for the medical profession. Within ENT I wanted to equip myself with the knowledge and experience necessary to become an expert in genetic hearing loss and novel therapeutics seeking to cure this type of disease.
From a personal perspective, when undertaking a PhD as a surgical trainee there are a lot of things to think about, and I spent time thinking carefully about the personal impact of trying to balance a surgical and academic career. For me, the prospect of being a surgeon scientist is a fantastic way of building an impactful, enriching and fulfilling working life while bringing a diversity to my day-to-day activities that will help maintain longevity in my career.
Thoughts on the fellowship in terms of the opportunity it offered to pursue being a surgeon-scientist, which is otherwise a rare opportunity.
My project is focused on understanding more about Norrie disease. This is a rare X-linked recessive disorder resulting in congenital blindness and progressive hearing loss. The Sowden lab is working to better understanding the mechanism of this disease and develop a gene therapy for the hearing loss associated with this condition. I am in the first year of my PhD and have already learned so much about laboratory techniques, novel therapeutics, and translational science from my colleagues at the Institute of Child Health. I also maintain a close relationship with my clinical supervisor and regularly visit Great Ormond Street to join an operating list. I think this fellowship is among the best opportunities for surgeons to start their academic career, as it has been specifically designed to place fellows in translational research projects. This has provided me with a wealth of learning opportunities in both lab-based and clinical research and is a great environment to learn the ways in which surgeons can be at the forefront of bringing new science to surgical patients.
Why do you think it is an important role in the landscape of paediatric healthcare?
I think that the role of surgeon scientists is particularly important in paediatrics, as the opportunity for intervention is huge. There is amazing progress being made in finding new ways to diagnose and treat previously challenging conditions in this population, and surgeon scientists have a key role in ensuring this progress is actualised in clinical practice.
About the PhD Project
Project title: Cochlear gene therapy to treat progressive hearing loss in Norrie Disease
Surgical speciality: Ear, Nose & Throat Surgery
Supervisoru group: Jane Sowden, Robert Nash
This project will focus on the development of a gene therapy for Norrie disease to prevent progressive hearing loss.
Norrie disease is an X-linked condition, caused by mutation of the gene NDP. Boys with Norrie disease are born blind with severely disrupted retinal vasculature. Almost all develop progressive hearing loss that becomes profound. No curative treatment currently exists. Children with Norrie disease are regularly seen at Great Ormond Street Hospital (GOSH) after referral for congenital blindness and genetic testing. Our multidisciplinary research team comprising clinicians and scientists aims to address the challenge of finding treatments for Norrie disease and works together with the patient family led UK-based registered charity, the Norrie Disease Foundation UK.
NDP encodes a small secreted protein, Norrin that activates the canonical Wnt/b-catenin signalling pathway in endothelial cells to control retinal vascular growth. Norrin is also essential for normal function of the microvasculature in the cochlea with the later loss of sensory hair cells causing profound hearing loss.
This project will use a mouse genetic model of Norrie disease to evaluate molecular therapies for Norrie disease. We have studied the early stages of disease and established several assays to measure abnormalities of the cochlear vasculature and sensory hair cell that will be used to assess whether NDP gene replacement therapy ameliorates the cochlear phenotype.
The aim is to perform a pre-clinical gene therapy trial in the Ndp-KO mouse model using an NDP adeno-associated viral (AAV) vector designed for clinical use and direct cochlea injection based on the efficacy of a GFP tagged prototype vector already tested in our laboratory. We will deliver the human NDP gene sequence to the cochlea via intracochlear injection and measure the outcomes of prevention of hair cell death and hearing loss.
Jonathan Neville (2023-2027)

Jonathan graduated from King’s College London School of Medicine in 2018, where he completed an intercalated BSc in Medical Genetics in 2015. He was a paediatric surgery themed Academic Foundation Doctor in the North West London deanery, and then in 2020 was awarded an NIHR Academic Clinical Fellowship in paediatric surgery at the University of Southampton. During these three years his research was a mix of clinical studies and laboratory research at the Institute of Cancer Research. Jonathan completed a year of specialist registrar training at the Royal Alexandra Children's Hospital before starting his PhD at the Great Ormond Street Institute of Child Health in April 2024. His research focuses on investigating heterogeneity in neuroblastoma and the development of new techniques for surgical management of paediatric tumours.
Motivation for wanting to be a surgeon scientist.
Paediatric surgeon scientists are in a unique position to be able to directly investigate often rare and complex diseases which have a lifelong impact on the child. Research findings can be translated from the laboratory into the clinic and dramatically improve outcomes and quality of life for children. It is the combination of the varied pathology, the necessity for innovative and collaborative research methods, and the immense positive impact that paediatric surgeons can make to a child’s life that makes a career as a paediatric surgeon scientist so rewarding.
Thoughts on the fellowship in terms of the opportunity it offered to pursue being a surgeon-scientist, which is otherwise a rare opportunity.
The fellowship enables me to work within a world class institution at the cutting-edge of paediatric surgical science. The exceptional facilities, supervisors and teaching at the Institute of Child Health will allow me to develop my laboratory research skills.
Why do you think it is an important role in the landscape of paediatric healthcare?
Surgeon scientists can bridge the gap between the lab and the clinical environment. The role is vital to bring important questions from the hospital to researchers in the laboratory, and to translate new technologies and treatments from the laboratory to patients. It is a real privilege to be able to assist in advancing paediatric surgical care in this way.
About the PhD Project
Research project title: Investigating spatial and temporal tumour heterogeneity in neuroblastoma to improve surgical clearance and develop novel techniques for loco-regional control
Surgical speciality: Paediatric Surgery
Supervisors: John Anderson, Stefano Giuliani
PhD project abstract
Neuroblastoma is a paediatric cancer arising during development in the neural crest. It has a wide range of clinical outcomes, from spontaneous remission to aggressive metastatic disease. Neuroblastoma is responsible for 15% of all childhood cancer deaths, and five-year survival rates are 40 – 50% in high-risk disease. Prognosis has not dramatically improved in the last 20 years.
Studies have identified that certain molecular alterations and tumour immune microenvironment (TIME) changes are associated with poorer outcomes. However, there is a high degree of spatial and temporal heterogeneity. Chromosomal aberrations and druggable-target gene mutations are variable at diagnosis and relapse, suggesting ongoing clonal evolution. This evolution may cause heterogeneity in the TIME and cell surface marker expression.
Surgery remains a critical component in the multimodal management of neuroblastoma. Surgical resection is associated with complications and it can be challenging intra-operatively to discriminate neuroblastoma from non-cancerous tissue. Residual tumour associates with local recurrence and poorer outcomes. Fluorescence-guided surgery (FGS) is an evolving technology that enables surgeons to identify and remove tumour material using neuroblastoma-specific probes incorporating fluorophores. GD2-specific tracers have shown promise in pre-clinical studies. But they are limited by heterogeneity and GD2 is down-regulated in response to immunotherapy.
There is a paucity of evidence describing the heterogeneity of the molecular, TIME and cell surface marker profiles in neuroblastoma. In this study we will perform imaging-guided, multi-regional biopsies of diagnostic and post-treatment tumour material. Samples will undergo genomic, transcriptional and multiplex spatial analysis. These profiles will be integrated to generate phenotypes predictive of clinical outcome. Multiplex imaging will be used to evaluate the TIME and identify new targets for FGS. We envision that the comprehensive mapping of neuroblastoma heterogeneity will enable the development of multiple FGS probes which can identify specific subclones. This would improve intra-operative decision making, allowing surgeons to identify areas of aggressive tumour and discriminate viable from non-viable tissue.
Amparo Saenz (2024-2027)

Originally from Patagonia, Argentina, I completed my neurosurgery training at Garrahan Hospital in Buenos Aires. In 2021, I relocated to London to undertake a Paediatric Neurosurgery Fellowship at Great Ormond Street Hospital (GOSH). This opportunity led me to pursue two additional fellowships in Paediatric Spine and Craniofacial Surgery. My passion for research has always been a driving force in my career, and in the UK, I discovered an ideal environment that allows me to continue my research endeavours while remaining actively involved in neurosurgery
Motivation for wanting to be a surgeon scientist: My motivation to become a surgeon-scientist stems from a deep desire to bridge clinical practice and research. I believe that by integrating these two disciplines, I can contribute to advancements in patient care while directly applying innovative research to surgical practice. This dual role allows me to not only treat patients but also to explore new frontiers in medical science, ultimately improving outcomes for future generations.
Thoughts on the fellowship in terms of the opportunity it offered: The fellowship provided a unique and invaluable opportunity to pursue my dual interests as a surgeon-scientist. This rare experience allowed me to immerse myself in advanced clinical training while also engaging in meaningful research. The structured environment, access to cutting-edge resources, and mentorship from leading experts made it possible for me to develop as both a clinician and a researcher, which is often difficult to achieve simultaneously.
Why it is an important role in the landscape of paediatric healthcare: The role of a surgeon-scientist is crucial in paediatric healthcare because it fosters a continuous cycle of innovation and improvement. By being directly involved in both surgery and research, surgeon-scientists are uniquely positioned to identify clinical challenges and develop targeted research questions. This approach leads to more effective treatments and better patient outcomes, ensuring that paediatric care remains at the forefront of medical advancements.
About the PhD project
Research project title: Chiari II brain malformation: role of cerebrospinal fluid
Surgical speciality: Paediatric Neurosurgeon
Supervisors: Prof. Andrew Copp and Mr Dominic Thompson
PhD project abstract:
Open spina bifida (OSB; often called ‘myelomeningocele’) is accompanied in most cases by the Chiari II malformation, in which hindbrain herniation leads to hydrocephalus. Other brain defects in Chiari II (e.g. neuronal migration disorders, hypogenesis of the corpus callosum) are common and underlie learning difficulties in many children with OSB. Cerebrospinal fluid (CSF) leaks from the OSB lesion, and has been implicated in causing the Chiari II malformation. While hindbrain herniation can be reduced by fetal surgery for OSB, the ‘higher’ brain defects are not prevented. This project will test the hypothesis that CSF composition may differ in OSB – due to fluid leakage and rapid replenishment – and that this may adversely affect neuronal formation (neurogenesis) and migration in the embryonic and fetal brain. CSF will be collected from children with OSB/Chiari II undergoing neurosurgery at GOSH, using CSF from other operations as controls. CSF will also be obtained during fetal surgery for OSB, and from a mouse genetic model of Chiari II that we recently developed (Cdx2Cre x Pax3flox). Composition of the CSF will be analysed using mass spectrometry-based proteomics, to detect differences between OSB and controls. To determine whether neuronal formation and migration are affected by CSF composition, brain slices will be prepared from human embryos supplied by the Human Developmental BiologyResource, and also from mouse embryonic brains. Cultures will be treated with CSF of different origins, and also with purified candidate proteins highlighted by the proteomic analysis. Neurogenesis will be measured using cell cycle methods (e.g. EdU labelling). Neuronal migration will be studied by immunolabelling with cell type-specific antibodies, and by Cre/loxP lineage tracing. This project aims to significantly advance our understanding of how Chiari II brain defects arise in children with OSB, and to suggest new approaches to prevention of these disorders.
Damjan Veljanoski (2025-2028)

Damjan Veljanoski studied medicine at St Bartholomews and The Royal London Hospitals before undertaking an Academic Foundation Programme in the North of Scotland and a neurosurgical fellowship in Oxford. He developed a strong interest in the applications of artificial intelligence (AI), leading him to pursue a National Institute for Health and Care Research (NIHR)-funded Academic Clinical Fellowship (ACF), with enveloped neurosurgical residency. His ACF research has focused on the applications of AI and neuroimaging techniques to neurosurgery.
Motivation for wanting to be a surgeon scientist.
I applied to the Lewis Spitz PhD programme because I want to contribute to life-changing work for children with Lennox-Gaustaut syndrome and their families, whilst undertaking research that has positive potential outcomes for all children with epilepsy. This PhD provides an opportunity to translate my current NIHR ACF research and skillset in neuroimaging, machine learning and data science to paediatric epilepsy research at GOS ICH. The prospect of applying these skills to uncover neural networks in children with epilepsy and thus guide deep brain stimulation is hugely exciting. The implications of characterising these networks are vast and it represents one of the obstacles in our understanding and treatment of paediatric epilepsy.
Thoughts on the fellowship in terms of the opportunity it offered.
I am hugely excited by the chance to work with such an aspirational and inspirational supervisory team. Their outstanding and broad expertise fully realises the potential to be both academically and surgically excellent scientists. Their contributions to paediatric neurosurgical research are testament to the unique value of surgeon-scientists and the programmes that support them, and this fellowship will provide the training I need to hopefully follow in their footsteps.
Why is it an important role in the landscape of paediatric healthcare?
I believe that bridging research and clinical practice is essential to improving surgical outcomes, reducing invasive diagnostic procedures, and personalising treatments. These issues are critical in paediatric healthcare, where any interventions can affect a child's whole life from that point onwards. Working at the intersection of neurosurgery, neuroimaging and AI, I hope to contribute to the development of bespoke clinical pipelines and precision neurosurgical techniques that can directly improve care for patients and their families.
Projects portfolio 2023-2025
You can read through the latest portfolio of projects that was on offer as part of the Lewis Spitz PhD Programme. While no further calls are currently planned, you can reach out to the supervisory groups to explore an opportunity to apply for external fellowships, such as MRC and NIHR.
Cardiothoracic surgery
Academic supervisor: Deborah Ridout
Clinical supervisors: Victor Tsang Consultant Cardiac Surgeon
Additional supervisors and collaborators: Katherine Brown, Nigel Drury, Sonya Crowe, Anusha Jegatheeswaran
The post-operative survival rate of paediatric cardiac surgery is now >98%. This is a fantastic achievement however, there is now a focus on improving longer-term survival and quality of life, especially amongst children with complex defects, who generally need to have more than one operation in early life. Our research group, based between Great Ormond Street Hospital and UCL, has undertaken research with population-based data related to paediatric cardiac surgery since 2010, including the development of national methods for risk adjustment and outcome monitoring. Recently we used national linked datasets that contain information about ~65,000 children with heart disease born between 2000 and 2022, to estimate the survival rates of children with nine heart defects selected by patients, parents, and clinicians as the most important ones. During the course of this population-based research, (Congenital Heart Audit: Measuring Progress In Outcomes Nationally, funded by the Department of Health and Social Care's Policy Research Programme), we noted that surgical treatment strategies vary. Variation occurs in the degree to which interventional cardiology versus surgical approaches are used, and the degree to which serial palliative versus single stage reparative procedures are used. The data also indicate that surgical reinterventions are common with complex congenital heart defects and vary in frequency.
In this PhD, the student will work within our experienced research group, to explore the variation in surgical approaches for selected complex two-ventricle heart defects, (pulmonary atresia, aortic stenosis, atrioventricular septal defect). The student will explore links between surgical pathways and longer-term patient outcomes, by cardiac condition. The student will assess quality of life in a sample of older children with these complex congenital heart conditions. The project ultimately aims to use advanced health informatics and phenotyping in congenital heart disease surgical treatments, translating any findings into future recommendations for personalised care of complex congenital cardiac malformations.
Ear, nose and throat
Academic supervisor: Christopher O’Callaghan
Clinical supervisor: Colin Butler, Consultant Paediatric ENT Surgeon
Additional supervisors and collaborators: Rob Hynds, Elizabeth Maughan, Richard Hewitt
Epidermolysis bullosa (EB) in children is a rare genetic disease mainly affecting the skin. Treatment strategies for EB include replacing the affected epidermis with gene-corrected epithelium. Clinical studies using this approach has been shown to be effective for external skin. Airway involvement in EB is very rare but affected patients experience extensive inflammation, scarring and narrowing of the airway. Currently there are no treatments for airway involvement in EB other than symptom control. These patients often succumb to airway problems, as such, there is an ongoing need for treatments that address this unmet clinical need.
At Great Ormond Street Hospital, a cohort of children with EB have mutations in LAMA3 gene. Our team have successfully cultured epithelial basal cells from their upper airways and gene-corrected them using a lentiviral approach. Expression of wildtype LAMA3 cells restores cell adhesion to levels seen in healthy donors. This project aims to deliver gene-corrected autologous cells to children with airway disease, as tissue engineered sheets. This PhD project addresses current hurdles to clinical application, focusing in identifying optimal methods to improve transduction efficacies and tissue engineering methods for long-term engraftment.
The PhD candidate will work primary airway epithelial cells from patients, creating a lentiviral construct that will be specifically optimised for airway basal cells which will be progressed for potential clinical delivery. The proposal will further test preconditioning methods in an airway surgical model, to determine the optimal methods for engraftment of autologous epithelial cells. The results will be relevant to early phase human clinical studies involving gene-corrected epithelial cell transplantation in the airways. It has also significant applicability to engineering airway constructs for other disease processes of the airway, as such has significant applicability to surgeon scientists in this field.
Neurosurgery
Academic supervisor: Gabriel Galea
Clinical supervisor: Dominic Thompson, Consultant Paediatric Neurosurgeon
Terminal Myelocystocele (TM) is a closed spinal dysraphism with largely unknown aetiology and heterogenous presentation. It is a highly complex condition associated with both spinal neurological deficits and malformations of other organs, including cloacal exstrophy and musculoskeletal abnormalities. Unlike open spina bifida, the effectiveness of its prevention by folic acid is unknown and fetal surgery is not beneficial for individuals who have it. Great Ormond Street Hospital is a National referral centre for the management of this condition, the project’s clinical supervisor has reported advances in its post-natal neurosurgical management (Quong et al, Int Soc Ped Neurosurg 2015) and spinal neurosurgery is performed in approximately two cases per year. The primary supervisor’s group has recently characterised a transgenic mouse model which recapitulates many of the spinal and extra-spinal features commonly seen clinically in patients who have TM. This mouse model provides the first experimental evidence of a cellular signalling pathway underlying development of this condition: abnormal spinal cord dorsoventral patterning secondary to deficient Fibroblast Growth Factor (FGF) signalling.
The proposed project will i) use a comparative pathology approach to determine the fetal therapeutic window during which spinal neural function may be rescuable, ii) test potential treatments in our pre-clinical model, iii) develop human models of the condition using stem cells or fetal tissue slice cultures, iv) identify patient cohorts with clinical features broadly attributable to FGF disruption, and v) advance our ability to provide genetic diagnoses for individuals affected by TM.
Academic supervisor: Chris Clark
Clinical supervisor: Kristian Aquilina, Consultant Paediatric Neurosurgeon
Additional supervisors: David Carmichael
Adamantinomatous craniopharyngiomas are rare tumours that arise in the sellar and suprasellar regions in children and adults. Although biologically benign, their involvement of the pituitary gland and stalk, as well as the optic apparatus and the hypothalamus often leads to severe disability. In particular, hypothalamic injury causes a metabolic syndrome characterised by obesity, as well as fluid and electrolyte disturbances, eating disorders, reduced energy levels and severe impairment of memory and education. It is also associated with a shorter life expectancy. The ideal treatment for craniopharyngiomas is complete surgical resection, but involvement of the hypothalamus often precludes this, with preference to hypothalamus-sparing partial resection plus radiotherapy or radiotherapy alone. Radiotherapy is associated with a long-term risk of new malignant brain tumours as well as vascular disease. In addition, the tumour recurrence rate after radiotherapy may be up to 30%.
The decision regarding role and extent of surgical resection is therefore crucial and is currently made on the basis of standard MR imaging. We propose to use advanced MR imaging in a 7T MRI scanner to define the hypothalamus and its efferent tracts. We plan to recruit 30 patients with new or recurrent craniopharyngioma over the course of the PhD and undertake pre- and post-operative advanced MR imaging to determine the extent of hypothalamic nuclear injury and involvement of its principal outflow tracts, particularly the fornices, the mammillothalamic tracts and the mammillotegmental tracts. This will be correlated with clinical status pre-operatively and at follow up. We will also carry out a retrospective review of the imaging of children with craniopharyngioma who have already undergone treatment and where possible will evaluate the available imaging using advanced multi-shell tractography and fractional anisotropy. We aim to identify novel imaging biomarkers that will be useful in surgical decision-making and preventing hypothalamic injury in these children.
Academic Supervisor: Darren Hargrave
Clinical supervisor: Kristian Aquilina, Consultant Paediatric Neurosurgeon
Additional supervisors: Karin Straathof; Elwira Szychot
The project focuses on both the neurosurgical and the translational aspects of two planned inter-related clinical trials in high-risk paediatric brain tumours utilising novel drug delivery techniques. The first of these is the funded CARMIGO study which has recently opened at GOSH and will evaluate a specific anti-GD2 CAR T cell developed at UCL in diffuse midline gliomas (DMGs), which have a dismal prognosis. This first in human brain tumour study will administer CAR T cells intravenously and directly into ventricular CSF via a surgically implanted Ommaya reservoir. The latter will give direct access to CSF for the study of related biomarkers.
The second trial being developed is a convection enhanced delivery (CED) trial using four implanted microcatheters in a chronic delivery system of a novel agent directly into paediatric brain tumours. This will allow the drug to be delivered into the tumour, bypassing the blood brain barrier. With this implantable system multiple and regular injections of drug are possible without the need for multiple surgical procedures. Novel software will be used to position the catheters stereotactically in a way that optimises drug distribution within the tumour. This will be evaluated and quantified on sequential MR imaging. We also plan to implant an Ommaya reservoir through which drug will be injected into the CSF. It is hoped that this will reduce the incidence of tumour dissemination through the CSF. In this study we will also explore the use and value of tumour biomarkers in the CSF.
This project will allow a neurosurgical trainee to participate in novel research into unresectable brain tumours in children, including translational biomarker studies, and learn new techniques which are expected to become essential to surgical neuro-oncology in the near future.
Academic supervisor: Konrad Wagstyl
Clinical supervisor: Martin Tisdall, Consultant Paediatric Neurosurgeon
Epilepsy is a complex neurological disorder affecting millions of children worldwide. Seizures are often accompanied by a range of comorbid conditions, including Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), depression, and intellectual disability. These symptoms significantly impact the physical, cognitive, emotional, and social health of affected children. However, the underlying neurobiological mechanisms connecting focal epilepsy, comorbidities, and potential treatment interventions remain inadequately understood.
Epilepsy is a disorder of disrupted brain networks. Paediatric focal epilepsy is often caused by structural malformations which disrupt brain networks leading to both seizures and comorbidities. However, precise networks underpinning these symptoms are poorly characterised. This PhD project aims to address this knowledge gap through a multidisciplinary approach that combines invasive and non-invasive techniques to comprehensively map and modulate disrupted brain networks.
Project 1: Mapping and Modulating Thalamic Involvement in Paediatric Focal Epilepsy
This project's objective is to systematically investigate the role of thalamic nuclei in epileptogenic networks and assess the impact of thalamic deep brain stimulation (DBS) on cortical neurophysiology in paediatric focal epilepsy. The key outcome measures include identifying thalamic nuclei involvement in seizure networks and evaluating the effects of thalamic DBS on cortical brain network connectivity.
Project 2: Lesion-Symptom Network Mapping of Comorbidities in Focal Epilepsy
The goal of this project is to analyse the associations between lesion location, disrupted functional networks, and comorbidities in paediatric focal epilepsy. This will involve identifying lesion-related functional networks associated with common comorbidities and developing models to quantify the likelihood of developing comorbidities based on lesion locations.
The projects will utilise advanced neurosurgical, neuroimaging and analytical techniques and to advance our understanding of seizures and associated comorbidities in paediatric focal epilepsy. This research has the potential to inform personalised treatment strategies, potentially transforming the care of children with focal epilepsy, and providing unique contributions to the broader field of neuroscience.
Ophthalmology
Academic supervisor: Jane Sowden
Clinical supervisor: Robert Henderson, Consultant Ophthalmic Surgeon
Additional supervisors and collaborators: James Wawrzynski, Nicola Elvassore, Damien Yeo
This project will focus on the development of a cell therapy for retinal dystrophy using tissue engineering approaches. Diseases of the retina, resulting in the death of the photoreceptor cells are a leading cause of irreversible blindness. Children with inherited retinal dystrophies face progressive loss of vision.
In this project retinal imaging will be used to assess cell degeneration and to determine the optimal time period for intervention. Novel micro-engineering approaches will be used to create a human retinal tissue patch that could be used to repair the retina. As the inner retinal neurons and optic nerve that transmit visual information to the brain remain largely intact, connecting a new patch of photoreceptors could restore light perception to people with retinal dystrophy. Human pluripotent stem cells will be differentiated in vitro into retinal organoids that resemble developing retinal tissue and produce new cone and rod photoreceptor cells. Different approaches will be investigated to grow layers of photoreceptor cells on novel microengineered biocompatible scaffolds and to evaluate the biocompatibility of the stem cell-derived photoreceptor cell patch in animal models.
The project will suit a candidate with an interest in stem cells, retinal development and disease as well as therapeutic development for retinal dystrophy. The research fellow will be trained in retinal organoids from human pluripotent stem cells, tissue engineering using microengineering technologies and animal model characterization. The position will best suit a candidate with some experience in Ophthalmology and retinal examination (commencing ST3-5 at the start of the project) who will also attend the paediatric inherited retinal disease clinics at Great Ormond Street to gain an understanding of the progress of inherited retinal disease.
Academic supervisor: Ameenat Lola Solebo
Secondary supervisor: Jugnoo Rahi
Clinical supervisor: Chris Lloyd, Consultant Ophthalmic Surgeon and Paediatric Ophthalmologist
Additional supervisors and collaborators: Joe Abbott; Damien Yeo; Jessy Choi
Childhood cataract is the most important cause of global avoidable childhood blindness. Early and appropriate intervention, achieved in many setting through universal screening of newborns, is key to avoiding visual disability for affected children.1 Despite significant advances in our scientific understanding of supporting post-operative visual rehabilitation, alongside significant improvements in surgical techniques and correction of surgically created focusing power deficits (refractive errors), a notable proportion of children still fail to achieve good vision – half of all children with bilateral cataract have moderate visual impairment or worse, half of all children with unilateral cataract have severely impaired vision or worse in the affected eye, and one in five children develop a secondary, sight threatening glaucoma.
There are key evidence gaps on the child and intervention specific determinants of long term outcomes for children who have undergone cataract surgery.2 As childhood cataract is uncommon, a key challenge to research in this area is the need to undertake research across large, usually national level, populations, usually comprising children managed in specialist tertiary centres. Within the UK many of these centres are aligned to an NIHR Biomedical Research Centre. We propose to harness the power of data science to develop robust and validated algorithms based on these determinants would support decisions on frequency and duration of follow up following surgery (by identifying those groups who are high risk for adverse outcomes).
The project offers an unique opportunity for an ophthalmic surgeon in training to acquire academic skills and training in epidemiology and data science through a project that has high translational impact.
Academic supervisor: John Anderson
Clinical supervisor: Richard Bowman
Retinoblastoma (Rb) is the commonest form of childhood eye cancer and the commonest cause of death from eye cancer worldwide, but almost no-one dies in richer countries.
Liquid biopsy is a new technology looking at fragments of cancer DNA in blood or other body fluids which could replace having to a surgical biopsy to determine what type of cancer is present, how far it has spread and what treatment should be given. This has been applied to Rb but mainly to fluid from the eye. This still requires surgery and potential spread of tumour outside the eye. A blood test would be simpler and safer.
Exploratory work on using blood would best be carried out in children whose disease has spread beyond the eye which only occurs in poorer countries. These countries badly need research into how to improve management of advanced disease. Hence this is a perfect scenario for north south collaboration. The project will compare existing with new technologies to compare them for feasibility and sensitivity of detection of tumour DNA. This will facilitate the development of scaled down affordable tests to translate into clinical practice
Plastic and reconstructive surgery and Craniofacial surgery
Academic supervisor: Patrizia Ferretti
Clinical supervisor: Neil Bulstrode, Consultant Plastic and Reconstructive Surgeon
We are seeking an enthusiastic and able PhD student to join our established research team made up of highly experienced and renowned academics and clinical supervisors.
Our clinical aim is to develop a viable stem cell and tissue engineered cartilage that can be used successfully to reconstruct children’s ears and faces.
The reconstruction of ear and facial deformities require harvesting tissues from other areas of the body such as cartilage from the rib and ear. These donor sites are painful and can affect form and function. We intend that one day this will not be necessary.
We will compare stem cells from different sources including umbilical cord, paediatric abdominal fat and those derived from reprogrammed healthy somatic cells. We will optimise the environment where the stem cells can multiply, grow and differentiate into cartilage. These cells will be seeded into different scaffolds and culture conditions and will be examined for their ability to survive and acquire cellular, molecular and mechanical properties similar to native cartilage.
Specific shapes will be generated either by using moulds or by using a “bioprinter”. The properties of the bioengineered cartilage will be assessed using a range of tests available in our laboratories. The preparation and handling of selected cartilage constructs will be further developed under conditions suitable for clinical use. The ability of these constructs to survive the effects of being implanted will be tested as the next step on the journey to develop an ear shaped cartilage substitute so that we do not need to take rib cartilage from the child.
The successful candidate will be mentored, closely supervised and supported to ensure they will acquire new interdisciplinary skills, broad experience, scientific and surgical rigour.
Specialist Neonatal and Paediatric Surgery (SNAPS)
Academic supervisor: Conor McCann
Clinical supervisor: Paolo De Coppi, Consultant Paediatric Surgeon, Nuffield and NIHR Research Professor
Hirschsprung disease (HSCR), a life-threatening intestinal disorder affecting 1 in 5000 live births, is caused by the absence of enteric neurons in the distal bowel, which loses propulsive gut motility and ultimately results in intestinal obstruction. The current treatment is surgical resection of the affected bowel. Whilst lifesaving, this surgical treatment often results in patients experiencing life-long gastrointestinal problems including constipation, faecal incontinence, and enterocolitis, which significantly contribute to poor quality of life.
Recent pre-clinical evidence in animal models suggests that human pluripotent stem cell (hPSC)-derived enteric nervous system (ENS) progenitor transplantation, aimed at replacing lost neurons, is a potentially viable therapy. These data provide a strong basis for further translational investigation of this novel cell therapy. However, a major limitation, which precludes clinical application, remains a lack of knowledge surrounding the integration of hPSC-derived ENS progenitors in human tissue and the effects of immunosuppression on the efficacy of any ENS progenitor therapeutics.
The aims of this project are to: (i) Evaluate the ability of hPSC-derived ENS progenitors to integrate within human HSCR patient-derived gut samples in a novel ex vivo culture system (ii) Examine the effects of current clinical immunosuppression protocols on hPSC-derived ENS progenitors and (iii) Generate “universal” hPSC-derived ENS progenitors to overcome potential immune response barriers.
This project sits at the translational interface between basic and clinical science by making use of surgically resected human HSCR discard tissue as the foundation of its basic research investigation. As such, the results of this project will be directly translatable, informing future efforts to bring hPSC-derived ENS progenitors to the clinic. The novel data and tools developed through the course of this project could potentially transform approaches to cell therapy treatments in the intestine and beyond.
Academic supervisor: Simon Eaton
Clinical supervisor: Stavros Loukogeorgakis, Consultant Neonatal and Paediatric Surgeon, Associate Professor
Additional supervisors: Evangelos Mazomenos, Danail Stoyanov, Susan Shelmeridine, Simon Hannam, Maria Chalia
Necrotising Enterocolitis (NEC) is a severe neonatal condition with significant morbidity and mortality. Timely surgical intervention for NEC is challenging due to ambiguity in presentation, limited access to surgical/radiologic expertise in many neonatal units and difficulty in arranging in transfer to a surgical centre when surgical expertise is not available on site. Consequently, many infants with NEC die without having surgery.
We intend to devise a multimodal AI algorithm utilising clinical and imaging data that facilitates the diagnosis of NEC in non-specialist centres. We aspire to address the problems created by limited human expertise in the field and facilitate earlier diagnosis and transfer to a surgical centre. Furthermore, we currently struggle to risk stratify NEC and determine which patients would benefit from earlier surgical intervention and an AI based algorithm may help predict the need for early surgery. The outcomes from this study will should confirm transferability of the technology and facilitate approval for integration of the algorithm in the NEC detection workflow locally and nationally
Academic supervisor: Simon Eaton
Clinical supervisor: Paolo De Coppi, Consultant Paediatric Surgeon, Nuffield and NIHR Research Professor
This project aims to upscale our existing model to provide a functional, tubular, tissue-engineered conduit for replacement of an oesophageal deficit in a porcine long-gap OA model. This will act as an in-vivo feasibility study prior to proceeding with phase I clinical trials in humans for the treatment of long-gap OA.
Mini-pigs share anatomical and physiological similarities with humans and therefore make size-matching by weight appropriate for future translational use. Additionally, they are known to have better tolerance to surgical interventions than rabbits and do not practise coprophagy, making them the ideal choice of animal model. The overall aim of this PhD is to determine the potential of our tissue engineered oesophageal solution to be used for longer oesophageal grafts. In order to achieve this, the PhD student will develop methods to track cells and extracellular matrix from a tissue engineered graft which is then implanted in vivo.
Urology
Academic supervisor: David Long
Clinical supervisor: Navroop Johal, Consultant Paediatric Urologist
Additional supervisors: Charlotte Dean
Bladder exstrophy is a rare disease characterised by widely separated abdominal muscles and pelvis, an open exposed bladder and abnormally developed genitals in boys and girls. There are various strategies for treating bladder exstrophy, but all involve major reconstructive surgery. However, outcomes for the surgery are poor with even high-quality centres only capable of helping these children attain urinary continence in 25% of patients. On top of this, a proportion of these children will also develop kidney damage, which is a lifelong medical burden in these patients as well as the psychological impacts arising from concern about the function and appearance of their genitalia.
The root cause of the poor outcomes in bladder exstrophy is that surgical interventions do not reverse the underlying damage to the bladder that impairs its normal function. Therefore, new strategies are required. Work from our laboratory and clinical teams has focussed on normal and abnormal function of the muscles in the bladder. We have shown that most of the bladder muscles are replaced by scar tissue in exstrophy. This occurs via a process called fibrosis, which is also implicated in many other conditions; hence there are a number of new drugs being developed to treat fibrosis which have not yet been tested in exstrophy. Indeed, in pre-clinical studies of other bladder disorders we have found exciting new anti-fibrotic medicines which can reduce bladder scarring and improve its ability to recover and function normally. In this project, we aim to examine if anti-fibrotic drugs can be used as a treatment for bladder exstrophy. We will do this by taking part of the abnormal bladder that is removed during routine exstrophy surgery and cutting it into slices which will be cultured in a dish. We will then use this as a model to test drugs to stop (or reverse) fibrosis in bladder exstrophy. Collectively, this translational project will identify new therapies that could be used clinically in the future to treat bladder exstrophy.
Academic supervisor: David Long
Clinical supervisor: Naima Smeulders, Consultant Paediatric Urologist
Additional suprvisors: Tanzina Choudhury; Kathy Pritchard-Jones, Daniyal Jafree, Reem Al-Saadi
This PhD project aims to study the invasion patterns of blood vessels into kidney cancers in children, and the clinical and pathological implications of this invasion. To achieve this, the project includes the following objectives:
- Using 3D imaging to profile invasion patterns in paediatric renal cancers: by harnessing a novel technique to perform 3D imaging of vasculature in human tissues excised after surgery, the student will identify blood vessels in different types of renal cancer (Wilms tumour, malignant rhabdoid tumour of the kidney, renal cell carcinoma) and correlate these with clinically important outcomes for patients including metastasis, tumour recurrence and survival.
- Studying invasiveness of blood vessels into paediatric renal cancers ‘in a dish’: The student will isolate tumour cells from the different kinds of kidney cancer described above. Having achieved this, the student will utilise engineered blood vessels developed in our laboratory and develop an assay to study how blood vessels invade kidney tumours in vitro, and if this varies between different kinds of tumour
- Does chemotherapy impact the invasion or patterning of blood vessels into paediatric renal cancers?: The student will compare patterns of blood vessel invasion in children who have received chemotherapy before surgery as compared to after surgery. By developing and utilising trans-Atlantic collaborations the student will acquire chemotherapy-naive tumour samples, and pre- and post-chemotherapy samples will be compared for the presence and patterning of blood vessels to see how these drugs impact tumour vascular patterning.
This PhD project provides a unique opportunity for a trainee interested in paediatric oncology surgery to develop laboratory skills at the cutting-edge of science whilst answering fundamental clinical questions about how the tumour microenvironment impacts outcome of children with cancer.
Projects selected by successful PhD candidates in Rounds 23/24 and 24/25
Academic supervisor: Jane Sowden
Clinical supervisor: Robert Nash, Consultant Paediatric Otolaryngologist
Additional supervisors: Aara Patel; Deepak Chandrasekharan; Waheeda Pagarkar
This project will focus on the development of a gene therapy for Norrie disease to prevent progressive hearing loss.
Norrie disease is an X-linked condition, caused by mutation of the gene NDP. Boys with Norrie disease are born blind with severely disrupted retinal vasculature. Almost all develop progressive hearing loss that becomes profound. No curative treatment currently exists. Children with Norrie disease are regularly seen at Great Ormond Street Hospital (GOSH) after referral for congenital blindness and genetic testing. Our multidisciplinary research team comprising clinicians and scientists aims to address the challenge of finding treatments for Norrie disease and works together with the patient family led UK-based registered charity, the Norrie Disease Foundation UK.
NDP encodes a small secreted protein, Norrin that activates the canonical Wnt/b-catenin signalling pathway in endothelial cells to control retinal vascular growth. Norrin is also essential for normal function of the microvasculature in the cochlea with the later loss of sensory hair cells causing profound hearing loss.
This project will use a mouse genetic model of Norrie disease to evaluate molecular therapies for Norrie disease. We have studied the early stages of disease and established several assays to measure abnormalities of the cochlear vasculature and sensory hair cell that will be used to assess whether NDP gene replacement therapy ameliorates the cochlear phenotype.
The aim is to perform a pre-clinical gene therapy trial in the Ndp-KO mouse model using an NDP adeno-associated viral (AAV) vector designed for clinical use and direct cochlea injection based on the efficacy of a GFP tagged prototype vector already tested in our laboratory. We will deliver the human NDP gene sequence to the cochlea via intracochlear injection and measure the outcomes of prevention of hair cell death and hearing loss.
Academic supervisor: Andrew Copp
Clinical supervisor: Dominic Thompson, Consultant Paediatric Neurosurgeon
In spina bifida (myelomeningocele), leakage of cerebrospinal fluid (CSF) has been implicated in the hindbrain herniation that characterises the Chiari II malformation. Other brain defects in Chiari (e.g. neuronal migration disorders) are common and underlie learning difficulties in many children with spina bifida. However, the cause of these brain defects is unknown.
In this project, the PhD student will test the hypothesis that CSF composition may differ in spina bifida (e.g. because of rapid fluid loss and replenishment), and this may adversely affect neuronal migration during embryonic and fetal brain development.
The student will collect CSF from children with Chiari II undergoing surgery, using CSF from children receiving surgery for other brain conditions as matched controls. CSF will also be obtained during fetal surgery for spina bifida. Compositional analysis of the CSF (e.g. by proteomics, metabolomics) will reveal any differences between spina bifida and controls. CSF will be studied in parallel in a recently developed mouse genetic model of Chiari II. To determine whether neuronal migration is affected by CSF composition, the student will prepare and culture brain slices from mouse embryos, with addition of different CSF samples, and analysis of neuronal migration by immunolabelling with cell type-specific antibodies. Human embryonic brain slices may be studied using material from the Human Developmental Biology Resource. This project aims to significantly advance our understanding of how brain defects arise in children with spina bifida, and to suggest new approaches to prevent these disorders.
Academic supervisor: Torsten Baldeweg
Clinical supervisor: Martin Tisdall, Consultant Paediatric Neurosurgeon
Additional supervisors: David Carmichael; Tim Denison; Chris Clark
Deep brain stimulation (‘DBS’) devices are long-term implants used to deliver stimulation directly to deep targets in the brain to alleviate the symptoms of neurosurgical disease. DBS is emerging as a therapy for children and adults with drug-resistant epilepsy, yet further evidence is required to reveal the mechanisms by which DBS effects epilepsy and to predict patient candidacy and treatment response at pre-operative patient selection.
This PhD will investigate brain network connectivity profiles associated with treatment success in children with Lennox-Gastaut Syndrome undergoing DBS of the centromedian nuclei of the thalamus. It will be intricately linked with the CADET Project: ‘The Children’s Adaptive Deep brain stimulation for Epilepsy Trial’, an upcoming clinical trial led by GOSICH. The CADET Project will implant 26 children with Lennox-Gastaut Syndrome with a next-generation DBS device called the ‘Picostim DyNeuMo’ – which has both brain stimulation and brain sensing capabilities (a ‘brain-machine interface’). Funding for this study is already secured.
The primary project of the PhD will be a prospective, observational neuroimaging study in collaboration with the Department of Bioengineering at Oxford University and the London Collaborative Ultrahigh Field Scanner (LoCUS) at Kings College London. High-field (7-Tesla) magnetic resonance imaging (MRI) will be performed on children recruited to the CADET Project and diffusion and functional MRI will be used to investigate alterations in thalamic connectivity. Using outcome data from the CADET Project, the PhD Fellow will investigate pre-operative imaging correlates of treatment response to refine DBS targeting strategies.
The PhD Fellow will have the opportunity to undertake secondary projects that utilise neurophysiological recordings acquired from scalp electroencephalography and thalamic recordings (local field potentials) acquired during the CADET trial. These data will allow us to study dynamic network-alterations associated with thalamic neuromodulation and uncover the therapeutic mechanisms of the treatment.
Academic supervisor: Silvia Schievano
Clinical supervisors: Juling Ong Consultant Craniofacial and Plastic Surgeon and Owase Jeelani Consultant Paediatric Neurosurgeon
Learn about Craniofacial Research Group
This project, a collaborative effort with the highly specialised Craniofacial Units of GOSH (London), Birmingham Childrens’ Hospital and Alder Hey (Liverpool) focuses on improving the understanding, diagnosis and treatment of craniosynostosis. This condition, impacting 1 in 2,000-2,500 newborns, is characterised by premature fusion of one or more sutures in the skull, and results in abnormal head shapes and several potential developmental problems.
In this study, we first aim to establish normative data for paediatric head volume and shape, including growth curves using statistical shape models based on machine learning algorithms. These will help with accurate quantification of deformities in craniosynostosis patients. Second, we will develop models to objectively measure the severity of deformities across various craniosynostosis types and analyse the changes that occur with growth and because of surgical interventions. The developed models will be incorporated into the creation of a secure, online platform, designed to analyse cranial deformities from CT scans, but also 3D photographs, offering a radiation-free, accurate method for evaluation of these conditions. The tool will enable early diagnosis, and consistent and objective pre and postoperatively assessments, facilitating personalised treatment strategies.
Patient and Public Involvement and Engagement activities will be crucial to our project. The involvement of patients and parents will ensure that the developed tools are user-friendly and meet the needs of both clinicians and families. This will empower patients/families with knowledge about the severity of the condition, and the potential outcomes of surgical (and non-surgical) interventions, allowing for more informed decisions.
By integrating advanced computational tools and methodologies into craniosynostosis clinical care, this research will support surgeons with standardised, quantitative information on the severity of deformities and optimised interventions strategies, reducing reliance on subjective assessments. This, in turn, will promote evidence-based decisions, ultimately improving the quality of care and long-term outcomes for children with craniosynostosis.
Academic supervisor: John Anderson
Clinical supervisor: Stefano Giuliani, Consultant Neonatal and Paediatric Surgeon
Additional supervisors: Sally George, Louis Chesler
Neuroblastoma is a paediatric cancer arising during development in the neural crest. It has a wide range of clinical outcomes, from spontaneous remission to aggressive metastatic disease. Neuroblastoma is responsible for 15% of all childhood cancer deaths, and five-year survival rates are 40 – 50% in high-risk disease. Prognosis has not dramatically improved in the last 20 years.
Studies have identified that certain molecular alterations and tumour immune microenvironment (TIME) changes are associated with poorer outcomes. However, there is a high degree of spatial and temporal heterogeneity. Chromosomal aberrations and druggable-target gene mutations are variable at diagnosis and relapse, suggesting ongoing clonal evolution. This evolution may cause heterogeneity in the TIME and cell surface marker expression.
Surgery remains a critical component in the multimodal management of neuroblastoma. Surgical resection is associated with complications and it can be challenging intra-operatively to discriminate neuroblastoma from non-cancerous tissue. Residual tumour associates with local recurrence and poorer outcomes. Fluorescence-guided surgery (FGS) is an evolving technology that enables surgeons to identify and remove tumour material using neuroblastoma-specific probes incorporating fluorophores. GD2-specific tracers have shown promise in pre-clinical studies. But they are limited by heterogeneity and GD2 is down-regulated in response to immunotherapy.
There is a paucity of evidence describing the heterogeneity of the molecular, TIME and cell surface marker profiles in neuroblastoma. In this study we will perform imaging-guided, multi-regional biopsies of diagnostic and post-treatment tumour material. Samples will undergo genomic, transcriptional and multiplex spatial analysis. These profiles will be integrated to generate phenotypes predictive of clinical outcome. Multiplex imaging will be used to evaluate the TIME and identify new targets for FGS. We envision that the comprehensive mapping of neuroblastoma heterogeneity will enable the development of multiple FGS probes which can identify specific subclones. This would improve intra-operative decision making, allowing surgeons to identify areas of aggressive tumour and discriminate viable from non-viable tissue.