Centre for Surgical Innovation, Organ Repair and Transplantation (CSIORT)

Head:  Professor Brian Davidson

• Prof of Surgery, UCL
• Consultant HPB and Liver Transplant Surgeon, Royal Free NHS Foundation Trust
• Head of UCL Centre, Surgical Innovation, Organ regeneration and Transplantation.
• Surgical trials lead, NE Thames
• Chair NIHR RfPB panel for London and SE

Basic science and translational Research

1. Smart surgery

The development of a system for image guidance during laparoscopic liver surgery. Involves integration of a 3 dimensional model produced from pre-operative CTs with the laparoscopic images obtained during laparoscopic liver surgery. Funded initially by the DoH/Wellcome Trust HIC fund which resulted in system development with further development and preliminary clinical evaluation currently ongoing (2020) and funded by NIHR i4i.

Collaboration : Wellcome Trust and EPSRC Institute of Surgical Sciences (WEISS). Prof Dave Hawkes, Dr Matt Clarkson, Prof Dan Stoyanov, Dr Dean Barret,  Prof K Gurusamy

2. Organ preservation and IR injury

Royal Free houses one of the 7UK Liver Transplant Units. Extensive programme of studies related to organ preservation and ischaemia reperfusion injury. Studies on mechanism of ischaemia reperfusion injury, machine perfusion (funded by NIHR i4i), immunology of IR injury and modulation by remote preconditioning. Ongoing work on endothelial biology in acute organ injury and the role of NGal in acute kidney injury following liver transplant.

Collaborators Prof Fuller, Prof Maini Immunology UCL, Mr Robertson Edinburgh, Prof Salama Nephrology UCL.

3. US Histotripsy and liver regeneration

This collaborative is focused on the major problem of chronic liver disease and the need for a method of liver regeneration. Studies on US Histotripsy of the liver are being combined with methods of isolating and delivering human stem cell therapies.

Collaborators: Prof Saffari, Engineering, Mr Froghi Surgery, Prof Quaglia Histopathology, Dr Rashidi ICH.

4. Pancreas IRE therapy

We are investigating the use of this novel therapy in the treatment of pancreas cancer. The mechanism is being explored and therapies for modulating response. A novel ex vivo perfusion model is being explored, immunological responses to IRE therapy evaluated and a new perfusion system developed with Engineering and EPSRC funding.

Collaborators : Prof Stoyanov, Dr Agostini, Dr Neil Clancy WEISS, Prof Maini/Stauss Immunology, Dr Tu Vinh Leung pathology.

Deputy Head of Centre - Mr Reza Motallebzadeh

• Associate Professor, Research Department of Surgical Biotechnology, Division of Surgery and Interventional Science, University College London, UK.
• Honorary Consultant Renal Transplant Surgeon, Royal Free London NHS Foundation Trust, London, UK.
• Head of Centre for Transplantation, Department of Renal Medicine, University College London, UK.

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  Research

1. Integrating immunological, metabolite and microbiome data to predict clinical outcomes in kidney transplantation.

Collaborators – Dr Bajaj-Elliot (GOS Institute of Child Heath, UCL) & Dr Pesenacker (Institute of Immunity & Transplantation, UCL)

The composition of the microbiota and their metabolites could elicit signals that promote either an enhanced or diminished immune response against a kidney transplant. We aim to develop a better understanding of the changes to the gut microbiota and metabolites produced by them that can predict the course and heterogeneity of alloimmune responses.

2. Human kidney extracellular matrix hydrogels as a natural 3D platform for bioengineered models of kidney fibrosis

Collaborators – Professor Norman (UCL Centre for Experimental Nephrology), Dr Mazza (Institute of Liver & Digestive Health), Dr Twomey (UCB Pharma)

The aim of this work is to develop, characterize, and validate a novel in vitro 3D human kidney organoid culture system ultimately aimed at screening for compounds capable of modulating the tubulointerstitial microenvironment crosstalk that perpetuates development of fibrosis in chronic kidney disease.

3. Development of a point-of-care assay for monitoring rejection after renal transplantation.

Collaborators – Professor Tiwari & Professor Balabani (Dept of Mechanical Engineering, UCL)

Development of a novel point-of-care device to monitor urinary chemokines serially in renal transplant recipients and identify recipients with incipient allograft injury. Immune-based biomarkers offer the potential for identifying patients at risk for graft rejection and for individualizing immunosuppression therapy.

4. Characterisation of tumour-infiltrating lymphocyte populations in colorectal cancer

Collaborator – Dr Alsughayyir (King Saud University, KSA)

Investigation of the prognostic significance of tumour-infiltrating lymphocytes (TILs) in patients with colorectal cancer, with characterisation by immunohistology and TCR repertoire analysis. By comparison to paired PBMC samples, the variation in diversity and clonality of TILs will be determined.

Clinical Trials

1. Surveillance of arteriovenous fistulae using ultrasound (SONAR study)

A prospective multi-centre observational cohort study to determine whether ultrasound surveillance can reliably predict arteriovenous fistulae failure in patients with chronic kidney disease

2. Anaesthesia Choice for Creation of ArtEriovenous FiStulae (ACCESs study)

A randomised controlled trial comparing clinical (one-year functional patency rate) and cost-effectiveness of regional versus local anaesthesia for primary arteriovenous fistula formation

3. Pre-Implantation trial of Histopathology In renal Allografts (PITHIA study)

An open, stepped-wedge cluster, randomised trial to determine if the introduction of a national pre-implantation biopsy histopathology service increases numbers, and improve outcomes, of kidney transplants performed in the UK.

Clinical trials run by the HPB and Liver Transplant Group:

RIPCOLT (completed) : The first human study of recipient ischaemic preconditioning in liver transplantation. LAVA (completed) : NIHR HTA

 

UK multi-centre trial of IRE therapy for locally advanced and unresectable pancreas cancer.

Single centre feasibility study on ward based goal directed fluid therapy following acute pancreatitis.

LAP-PIE : NIHR RfPB

The first randomised trial to evaluate goal directed fluid therapy following liver transplant

GAP (recruited and ongoing analysis) : NIHR RfPB

The first adequately powered trial comparing liver resection surgery with thermal ablation for the treatment of colorectal liver metastases. Multi-centre UK and Netherlands.

COLT (completed) : NIHR RfPB

Teaching Summary

1. Module Lead & Course Tutor for the Transplantation Science module of the MSc/MRes Programme in Human Tissue Repair and Surgical and Interventional Sciences (SURG0083: Transplantation Science)

2. Module Lead & Course Tutor for the Student Selected Component in Transplantation Sciences (MBBS Year 2 SSC: Transplantation Sciences, SSC110).

Group Members

Dr Amber Gintare Vaitkute – Post-doctoral research fellow (2020)

Project: Integrating immunological, metabolite and microbiome data to predict clinical outcomes in kidney transplantation

Funding: Inflammation, Immunity and Immunotherapeutics (III) NIHR UCL Hospitals Biomedical Research Centre grant

Fernando Yuen Chang – PhD Student (2020)

Project: Integrating immunological, metabolite and microbiome data to predict clinical outcomes in kidney transplantation

Funding:

• Inflammation, Immunity and Immunotherapeutics (III) NIHR UCL Hospitals Biomedical Research Centre grant
• St Peter’s Trust Royal Free Charity grant

Mohrah Alalshaikh – PhD Student (to start Sept 2020)

Project: High throughput genomic profiling of colorectal cancer tumour infiltrating leukocytes

Funding: King Saud University External Joint Supervision PhD Studentship