2015 Grants to a total of £220,000
Liquid biopsy for prostate cancer
In this experiment, Dr Rueda established the best technique for the extraction and identification of cell free DNA (cfDNA) from the blood of patients with relapsed prostate cancer. Unfortunately, there was no correlation between the cfDNA and the Gleason score of the cancer. Similarly, there was no change after salvage treatment and no correlation with the tumour burden. This technique is useful, but more work will have to done to identify specific markers of prostate cancer.
It provided the basis for Taimar Shah’s doctoral thesis.
Mr Hashim Ahmed, MRC Clinician Scientist in Uro-oncology, with Professor Mark Emberton, Mr. Taimar Shah, Dr Mark Linch. UCL Hospitals.
Investigating molecular markers in primary urethral and penile cancers
These cancers are rare but spread very quickly, resulting in a poor survival rate for the patients. UCLH has been designated as a referral centre so that cases are concentrated in a single unit. This improves patient care and allows research with the largest possible numbers.
A comprehensive database has been developed to identify all the relevant samples held in the pathology department and off site for affected men. Their pathology slides have been retrieved and reviewed to identify the tumour areas of interest. From these, it is hoped that biomarkers common between the two cancers will be found.
Mr Varun Sahdev, Mr Asif Muneer, Dr Alex Freeman. Departments of Urology and Pathology, UCLH.
Equipment for the Centre for Nephrology
A contribution has been made towards provision of a ‘state of the art’ confocal microscope and multiphoton microscope equipment for the imaging required in a wide range of biomedical research projects in the Centre for Nephrology. It is now in daily use.
Professor Robert Kleta and other researchers in the Centre for Nephrology.
CMOS camera for selective plane illumination microscopy
CLARITY is a novel and exciting technique for 3D imaging of the form and structure of the kidney and gut. It requires a special camera and the Trust has purchased one to enable the establishment of the technique in the Centre for Nephrology.
Dr Anselm Zdebik, Dr Joanna Marks, Dr Steven Walsh, Dr Felice Leung.
Examples of biopsy autofluorescence (all links on YouTube)
- Confocal LSM 3D image of Human Kidney Needle Core Biopsy
- MesoSPIM 3D render of Prox1_tdTomato mouse kidney axial hemisphere
- MesoSPIM 3D image of kidney lymphatic vessels
Biomarker discovery with gene chip analysis cell model systems for renal Fanconi syndromes
This study has been successfully completed. A very large amount of data was collected. Sophisticated computational tools such as STRING and DAVID were used for analysis. As expected, it was found that fatty acid-related energy production was affected in FRTS. It was confirmed that this was the main source of energy for the proximal tubular cells. Novel fatty acid biomarkers were identified which will be investigated in a future project. Incidentally, analysis of the ‘big-data’ sets revealed novel defects in expression amounts of genes in FRTS that were not directly related to fatty acid regulated energy production – material for future work.
J Am Soc Nephrol. 2018 Jul;29(7):1849-1858. doi: 10.1681/ASN.2017111179. Epub 2018 Apr 13.
Cell Rep. 2019 Dec 24;29(13):4407-4421.e5. doi: 10.1016/j.celrep.2019.11.066.
Dr Enriko Klootwijk, Dr Horia Stanescu, Professor Robert Kleta.
Metabolic detection of kidney cancer
It was hoped that kidney cancer in high-risk individuals could be identified by measuring one or more of the compounds from the citric acid cycle (TCA) in urine. Although a normal range was established for each of the analytes no statistically significant differences in analyte levels were observed in samples from people with tumours or inherited tumour syndromes compared with controls. On these data measurement of TCA components in urine is unlikely to be useful in the clinical assessment of patients with kidney cancer syndromes.
Dr Daniel Gale, Mr Michael Aitcheson. Centre for Nephrology and Department of Urology.
Sanger sequencing in idiopathic membranous nephropathy (iMN)
This study has now been completed. A variant of the PLA2R1 gene was present in 98% of people with membranous nephropathy. This compared to 17% in the controls. This supports the view that the variant is contributing to, or causing, membranous nephropathy.
Dr Horia Stanescu, Dr Steven Walsh, Dr Sanjana Gupta.
Detection of lymph node metastases in penile cancer: a comparison to imaging and traditional surgical dissection
Cancer of the penis is another rare cancer for which UCLH has been designated as the referral centre. The number of cases being referred to UCLH now makes it possible to begin meaningful research on this devastating disease. The most important clinical prognostic factor is whether or not the lymph nodes in the groin which are the first site of spread, are involved. At present this can only be discovered by removing the nodes which often causes serious morbidity. This project will evaluate the use of epigenetic biomarkers in the blood to see if they can be used to diagnose the lymph node spread. The result of the blood tests will be compared with traditional imaging and surgical removal and will be the subject of Dr Rodney’s PhD thesis.
Professor John Kelly, Dr Andrew Feber, Simon Rodney
2016 grants to a total of £119,277
Genetic aetiology of rare chronic kidney disease
DNA was isolated from individuals overseas with common chronic renal diseases that are rare in the UK. It is likely that a region of DNA has been identified that is a strong risk factor for development of renal dysfunction in the study population and which may be involved in some rare conditions in the UK.
Dr Ben Caplin, Dr Horia Stanescu. UCL Centre for Nephrology
Development of new filter membranes for haemodialysis
The project aims to widen the range of toxins that can be cleared from the body by developing new filtration membranes and enable the 2 million patients being treated to survive for longer and in better health. Work is progressing slowly but surely, due to covid.
Dr Andrew Davenport, Director of Dialysis Research, RFH, Dr Kwang-Leong Choy, Director of UCL Institute for Materials Discovery.
The role of Notch-2 signalling in antibody-mediated kidney transplant rejection
Transplantation is the recommended treatment for many patients with end-stage kidney disease and it can greatly improve the quality and length of life. Antibodies produced by the patient’s immune system are the commonest reason for a transplant ultimately failing. This project will develop a new way of detecting the antibodies, using donor tissue taken at the time of transplantation, and will see if changes in Notch-2 (a key receptor in body tissue) can influence production of these damaging antibodies.
Professor Alan Salama, Dr Ciara Magee and Professor H. Strauss, UCL Centre for Nephrology and UCL Institute of Immunity and Transplantation.
Targeted molecular characterisation of immune response in a prostate cancer model following minimally invasive therapy
If the cancer is contained within the prostate it can be treated with therapies using light or ultrasound to enhance the delivery of intravenously injected agents such as chemotherapy drugs directly to the cancer cells. When cells die through such treatments it is believed that the body reacts by mounting an immune response that makes more of them die and so makes this action even more successful. The project aims to understand this response and find treatments that harness the immune system and use it to kill these cells.
Dr Rifat Hamoudi, Ms Caroline Moore, Prof Alexander MacRobert, Miss Sandra de Pinillos Bayona. UCL/UCLH Departments of Urology, Pathology and Photochemistry/Photobiology.
Detection and characterisation of circulating tumour cells in renal cell carcinoma
As tumours grow, they can release cells called circulating tumour cells (CTCs) into the bloodstream, but in kidney cancer they have been difficult to detect due to problems in finding reliable markers. Two independent methods of isolating CTCs in renal cancer will be investigated. Measuring them could prove very useful as predictors of likely outcome for the patient and/or response to treatment.
Dr Joana de Azevedo Barreiros Briosa Neves, Dr Agata Nyga, Dr MaxineTran, Professor Mark Emberton. UCL/UCLH Urology, Oncology Division of Science and Interventional Science.
ELx50 microplate strip washer for image guided biopsy and biomarker testing in patients with prostate cancer
Microplate washers are used in many assays at cell level. This equipment was purchased by the Trust to test biological samples (urine, blood, plasma) for the presence of known and novel biomarkers in prostate cancer research.
Dr L M C Echeverria, Dr Haley Whitaker, Mr Hashim Ahmed, UCL/UCLH Urology & Centre for Molecular Interventio
2017 grants to a total of £120,419
Understanding renal Fanconi syndrome associated with a mutation in HNF4A
This was a project for a doctoral thesis and to expand the work on Fanconi syndrome in Professor Kleta’s laboratory (see outcomes above).
Enriko Klootwijk/Professor Robert Kleta.
Are the mechanisms for controlling post-prandial phosphate homeostasis different in obesity, diabetes and chronic kidney disease?
Part funding for this PhD project was for consumables. Application for funding from other sources has been made.
Dr Joanne Marks/Professor Robert Unwin.