St Peter’s Trust Research Projects
As a result of major technological advances in science over the last forty years it has become possible to discover how our bodies are regulated at the level of the different microscopically small cells that make up our various tissues and organs, and which hold our genetic material. The cell is the smallest functional unit that can operate more or less independently in any organism, and a human being is made up of millions of cells. Research at the cellular level has been funded by St Peter's Trust for many years, and important findings have been reported by the scientists and clinicians the Trust has supported - in diseases such as diabetes, renal stones, complications of renal failure, bladder malfunction and prostatic cancer.
Grants totalling £119,277 have been awarded in 2016 for the following projects:
CHRONIC KIDNEY DISEASE
There are epidemics of chronic kidney disease of unknown cause in many countries of the world, including the UK. Genetic experts at the Centre for Nephrology, RFH will collaborate with an international group of researchers by studying existing DNA samples from several hundred overseas patients to assess genetic variations that could be leading to susceptibility to the disease and use the findings for further research on genetic origins of the disease in the UK.
Dr B Caplin, Dr H Stanescu. UCL Centre for Nephrology.
IMPROVING HAEMODIALYSIS TREATMENT
A patient with kidney failure is unable to excrete waste products in the urine. These accumulate and cause harm in the body as a whole. Haemodialysis treatments remove these toxins by passing the patient’s blood through the dialyser. 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.
Dr A Davenport, Director of Dialysis Research, RFH, Dr Kwang-Leong Choy, Director of UCL Institute for Materials Discovery.
THE PROBLEM OF 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. However, despite scientific advances, antibodies produced by the patient’s immune system are still 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.
Prof A Salama, Prof H. Stauss, UCL Centre for Nephrology and UCL Institute of Immunity and Transplantation.
PROSTATE CANCER TREATMENT
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 R Hamoudi, Ms C Moore, Prof A MacRobert, Miss S De Pinillos Bayona. UCL/UCLH Depts of Urology, Pathology and Photochemistry/Photobiology.
RENAL CELL CARCINOMA
As tumours grow they can release cells called circulating tumour cells (CTCs) into the bloodstream, but in kidney cancer this has 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 J de Azevedo Barreiros Briosa Neves, Dr A Nyga, Dr M.Tran, Prof M Emberton. UCL/UCLH Urology, Oncology Division of Science and Interventional Science.
ELx50 MICROPLATE STRIP WASHER EQUIPMENT FOR IMAGE GUIDED BIOPSY AND BIOMARKER TESTING IN PATIENTS WITH PROSTATE CANCER
Microplate washers are used in many assays at cell level and the main objective here will be to test biological samples (urine, blood, plasma) for the presence of known and novel biomarkers and to validate them for indications of prostate cancer. A separate study of 600 patients is currently evaluating the role of MRI in men with clinical suspicion of prostate cancer. As well as magnetic resonance imaging it also holds blood and urine samples and prostate tissue from biopsies This provides a unique opportunity to find the most promising markers and use them in conjunction with MRI for improved diagnosis and treatment.
Dr L M C Echeverria, Dr H Whitaker, Mr H Ahmed, UCL/UCLH Urology & Centre for Molecular Intervention.
Grants to a total of £220,000 have been awarded in 2015 for the following projects:
Liquid Biopsy - using cell free DNA (cfDNA) and circulating tumour cells (CTC's) - in the diagnostic and treatment pathway for high risk radiorecurrent prostate cancer.
Every year over 9,000 patients with prostate cancer undergo radiotherapy. Although this is generally a very good way of halting the disease, like all treatments it can sometimes fail. In such cases some patients may be suitable for additional treatment to remove the tumour, using either high-intensity focused ultrasound that 'heats' or cryotherapy that 'freezes'. This project will aim to establish which patients could benefit from one of these treatments by measuring changes in the levels of cancer cells and cancer DNA in the blood.
Mr. H. Ahmed, MRC Clinician Scientist in Uro-oncology, with Prof. M. Emberton, Professor of Urology, UCL Hospitals. Mr. T. Shah, Dr M. Linch. £32,000.
Investigating Molecular Markers in Primary Urethral Cancer.
Such cancers are rare but spread very quickly, resulting in a poor recovery and survival rate for the patients. The researchers will study various protein markers known to be associated with cancer growth, spread and invasion, in order to examine where drugs and other therapies may be of help in improving outcomes. The preparation and analysis of the pathology specimens will be funded. Both Urology, and Cancer Treatment more generally, have now been designated as major referral centres at UCLH and it has become possible to see a sufficient number of rare cancers of this sort and undertake associated research.
Mr V. Sahdev, Mr. A. Muneer, Dr. A. Freeman. £10,000.
Detection of lymph node metastases in penile cancer: Evaluating the use of epigenetic biomarkers in the blood in comparison to imaging and traditional surgical dissection.
The number of cases of penile cancer being referred to UCLH make it possible to begin meaningful research on this rare but devastating disease. The key to treatment is assessing if the cancer is present in the glands of the groin (particularly as spread of the disease to these lymph nodes is the most important indicator of the likely length of survival time). Currently the only way to do this is to physically remove these glands, with potentially severe side effects. However, as the cancer will not have spread to the groin in the majority of these patients the procedure is causing associated harm with no benefit to many patients. This project seeks to develop a blood test which can detect signs of potential cancer cells in the lymph nodes pre-operatively and assess its viability in the clinical situation.
Prof. J. Kelly, Dr. A. Feber, Mr. S. Rodney (PhD student). £55,020.
Equipment for the Centre for Nephrology
A contribution 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.
Prof. Robert Kleta. £25,000.
CMOS camera for Selective Plane Illumination Microscopy
Purchase of equipment to establish CLARITY, a novel and exciting technique for 3D imaging of the form and structure of the kidney and gut.
Dr. A. Zdebik, Dr. J. Marks, Dr. S. Walsh, Dr. F. Leung. £12,225.
Biomarker discovery with gene chip analysis using cell model systems for renal Fanconi syndromes
The kidney contains cells that are important in the reabsorption of substances from the urine back into the blood. These specialised 'proximal tubular cells' need fatty acids as their source of energy. A malfunction of these cells results in a disorder called Fanconi renotubular syndrome. The team has shown that in patients with a specific form of the disorder fatty acids cannot be used properly and the resulting deficiency in energy production is the cause of the disease. Impaired energy also appears to be central to other common kidney disease and it is hoped that this research will provide explanations of other conditions too.
Dr E. Klootwijk, Dr H. Stanescu, Prof R. Kleta. £20,000.
Metabolic detection of kidney cancer
This cancer kills over 4,000 people each year in the UK, but if detected early it is treatable by surgical removal. Kidney cancers are often caused by a block within the cancer cell of the process by which sugars are broken down to release energy. This project will measure the urinary levels of compounds produced when this block occurs and find out whether this can be used to detect the cancer at an early stage. This will be done by studying a group of patients known to be at high risk of the disease who are routinely having surveillance kidney scans.
Dr D. Gale, Mr M. Aitcheson. £55,799.
Sanger sequencing in idiopathic membranous nephropathy (iMN)
This organ specific autoimmune disease is a major cause of the nephrotic syndrome and renal failure in patients in the UK. It is proposed to sequence the gene locus for the M-type Phospholipase A2 Receptor (PLA2R), as antibodies to it are able to cause disease and are present in 60-70% of patients with iMN. More than one form of the gene has been shown by Dr. Stanescu to confer a significantly increased risk of developing the disease. Fully sequencing the position of this gene on a chromosome could provide understanding of the likely effects that different forms of the gene have on the structure of the PLA2 receptor and the consequences that this has on its ability to produce an immune response.
Dr. H. Stanescu, Dr. S. Walsh, Dr. S. Gupta. £10,000.
St Peter’s Trust Research groups
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Past SPT achievements prior 2010
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