Research groups supported by St Peter’s Trust
Urology
To make initial contact with all research groups please contact [email protected]
Extended information on the main interests of each group is available below
Urology is a Centre of Excellence within the Research Department of Targeted Intervention
Head of Centre: Professor Caroline Moore
Basic Science
Dr Hayley Whittaker
Dr Andy Feber
Endoluminal Endourology (including stone disease):
Mr Simon Choong
Mr Daron Smith
Miss Sian Allen
Mr Vimosham Arumuham
Renal Cancer
Professor Marilena Loizidou
Ms Maxine Tran
Male reconstruction:
Professor Tony Mundy
Miss Daniela Andrich
Andrology and Genital Oncology:
Professor David Ralph
Mr Asif Muneer
Miss Pippa Sangster
Adolescent Urology and long-term follow-up:
Mr Dan Wood
Professor Sarah Creighton
Lee Mai Liao
Gunter de Win
Female, Functional and Restorative Urology:
Ms Tamsin Greenwell
Jeremy Ockram
Uro-Radiology:
Dr Clare Allen
Dr Alex Kirkham
Dr Doug Pendse
Professor Shonit Punwani
Nephrology
Director of Medicine: Professor Robert Kleta
Department of Renal Medicine:
Director: Professor Alan Salama
Deputy director: Dr Jill Norman
click here for extended material
Centre for Transplantation:
Dr Motallebzadeh
Dr Magee
Centre for Clinical Kidney Disease:
Dr Caplin
Dr Wheeler
Centre for Genetics
Professor Danny Gale
St Peter’s Professor of Nephology
Dr Horia Stanescu
Centre for Urological Biology
Dr Rohn
Centre for Physiology and Dialysis:
Dr Ben Walsh
Dr Joanne Marks
Centre for Experimental Nephrology:
Dr Jill Norman
Dr Ruan
Nephrology
To make initial contact with all research groups please contact [email protected]
Extended information on the main interests of each group is available https://www.ucl.ac.uk/nephrology/
Director of Medicine: Professor Robert Kleta
Director of Renal Medicine: Professor Alan Salama
Deputy director: Dr Jill Norman
Centre for Transplantation:
Dr Motallebzadeh
Dr Magee
Centre for Clinical Kidney Disease:
Dr Caplin
Dr Wheeler
Centre for Genetics
Professor Danny Gale – St Peter’s Professor of Nephology
Dr Horia Stanescu
Centre for Urological Biology
Dr Rohn
Centre for Physiology and Dialysis:
Dr Ben Walsh
Dr Joanne Marks
Centre for Experimental Nephrology:
Dr Jill Norman
Dr Ruan
Urology extended material – current interests and work of the research groups.
Urinary stone disease
The original St Peter’s Hospital was founded 1860 specifically to care for patients with stones in the bladder and kidneys. It is not surprising, therefore, that a great deal of research into these conditions has been funded by the St Peter’s.
Several new techniques for the removal of stones are being pioneered. Most recently, the group led by Daron Smith and Simon Choong have been working on safer ways of removing stones from the kidney in patients who were born with spina bifida. Kidney stones are commoner in these individuals because of their relative immobility and increased susceptibility to urinary infection. They will often have severe spinal curvature that makes access to the kidneys more difficult. All surgery is riskier because their respiratory reserve is poor and post-operative recovery is more difficult.
By adapting the techniques of minimally invasive surgery it has been possible to clear stones from the kidney with fewer complications and less need for post-operative intensive care.
Publication
Percutaneous Nephrolithotomy and Spina Bifida – Complex Major Stone Surgery?
Mitchell, S., Gurung, P., Choong, S., Morris, T., Smith, D., Woodhouse, C., Philp, T. J Endourol 2018; 10.1089/end.2017.0775
Another group of patients who have an increased risk of stones is those who have to store their urine in bladder reservoirs made from intestine, either because the natural bladder has been removed or because they were born wholly or partly without one. The stones occur in the intestinal bladder itself, can grow very quickly and get quite large. They often need an open operation for removal.
Investigations of the causes and means of prevention have been undertaken with the Reconstruction Unit by Rizwan Hamid and Dr Bill Robertson. With funding from St Peter’s Trust they found important differences in urine composition and diet between the patients who regularly formed stones and those who never did. On the basis of their findings it was found that relatively simple changes in diet had the potential to reduce the incidence.
Publications
- Hamid R, Robertson WG, Woodhouse CRJ. Comparison of biochemistry and diet in patients with enterocystoplasty who do and do not form stones. British Journal of Urology International. 2008;101:1427-32.
- Robertson WG, Woodhouse CRJ. Metabolic factors in the causation of urinary tract stones in patients with enterocystoplasty. Urological Research. 2006;34(4):231-8.
Urethral reconstruction
The male urethra is very vulnerable to stricturing as a result of infections, trauma and inflammatory diseases. Many forms of treatment have been used since written records of medicine first began. Scientific investigation has been a major subject for the St Peter’s group of hospitals and the Institute of Urology beginning with the work of Professor John Blandy and Mr Richard Turner-Warwick in the 1960s and 1970s.
Professor Tony Mundy and Miss Daniela Andrich and their team have developed surgical repairs much further and their work continues.
Current techniques of repair depend heavily on the use of autologous tissue and particularly on buccal mucosal grafting. But however successful they are, they have their limitations, firstly because they are not “natural” tissues for the urinary tract, and secondly because they require an invasive surgical procedure to implant them.
The team is developing a new approach using stems cells rather than autologous grafts as the treatment modality and minimally invasive endoscopic surgery rather than invasive open surgery to deliver them.
Preliminary results suggest that this should be successful, particularly in reducing side effects on sexual function.
They are applying for an NIHR grant to do a more extensive evaluation of the technique, specifically to see if the same durability of stricture control as that achieved with open surgery can be achieved without the side effects of the open operation.
Andrology and Genital Oncology
Oncology
Cancers of the penis and male urethra are very rare. In the past, the prognosis has been poor, in part because men were reluctant to discuss genital symptoms even with their doctor and partly because urologists saw too few patients to build expertise in management. They spread very quickly, resulting in a poor survival rate for the patients.
As part of the Government Cancer Initiative, 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.
The UCLH group are studying 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. A comprehensive database has been developed to identify all the relevant samples of urethral and penile cancer held in the pathology department. From these cancer biomarkers can be identified and related to the known outcome of the men from whom they were originally collected. It is hoped that some will be found that are predictors of outcome.
The biomarkers can also be compared between the two diseases (which have several pathological and clinical features in common) so that a common treatment strategy can be developed for them.
The St Peter’s Trust awarded a grant to Mr Varun Sahdev, Mr Asif Muneer, Dr Alex Freeman to support a major part of this work.
Andrology
The department has several areas of research related to erectile dysfunction and gender identity. At present, interest is focussed the relationship between cardiovascular disease and arteriogenic impotence. It is believed that they share a mutual pathophysiology. Onset of arteriogenic impotence may be marker for current or future cardiovascular disease.
Priapism
This condition is a persistent painful erection, which is considered a medical emergency. It has many causes including sickle cell disease, psychiatric medications and malignancies. The group at UCLH is now a tertiary referral centre for this condition and is leading the way in research. Three higher degrees have been obtained and many peer-reviewed publications have come from the research into the smooth muscle function of the penis and the ultimate management. Research is on going with a new radiological input.
Peyronie’s Disease
St Peter’s has a long history in research for this condition. Higher degrees and publications have resulted and currently the group are studding the possible mechanisms of the disease looking at myofibroblast transformation during the acute stage of the process. They are also looking at new drugs that can help prevent progression, in particular oestrogen modulators and phosphdiesterase inhibitors. Collaboration with Anglia Ruskin University with PhD fellows is on going.
Infertility
This is an active area of research where the group are studying the genetics of infertility. Research is on-going into men with genetic abnormalities such as Klinefelter’s disease, endocrine abnormalities and fertility preservation for patients undergoing cancer therapies. As cancer survival rates improve, long term outcomes in these patients has shown poor outcomes in terms of their fertility potential. Capturing these men prior to treatment to ensure cryopreservation or surgical sperm retrieval is vital. Research collaboration with Oncologists/Endocrinologist/Gynaecologists is underway to increase awareness and build links within these departments to provide the best possible care both before and after oncology treatments.
As animal research shows the potential of prepubertal stem cell preservation, we move forward in investigating the use in humans to provide children with various conditions affecting fertility with the potential of parenting
Gender dysphoria research
The unit has been dealing with this condition for 40 years and is still making advances in the surgical therapy. Other projects involve the association of testosterone therapy and uterine cancer and fertility preservation in adolescents.
Penile transplantation
After the initial success with the worlds first 4 penile transplants, this unit is preparing to develop a programme in combination with the transplant physicians to offer this to patients who have either lost their genitalia from injury or treatment or have congenital abnormalities that warrant transplantation. This is a new area for the hospital, which will generate much interest and research.
Adolescent and long-term follow-up
Children born with the major congenital anomalies of the genito urinary tract, such as exstrophy, posterior urethral valves and disorders of sex (DSD) development are looked after in paediatric units from birth onwards. Up until the 1960s, many of them would have died in childhood. With modern care, the large majority will have a normal life expectancy. However, they will continue to require specialised care through adolescence and adulthood.
There is a strong link between UCLH and the Hospital for Children Great Ormond Street (GOSH) to provide joint care for patients passing through puberty and a seamless move to lifelong adult care in the Adolescent Unit.
Members of the Adolescent unit have undertaken extensive research into the management and outcomes of the patients, in collaboration with nephrology, psychology and gynaecology departments.
The St Peter’s Trust has, directly or indirectly, funded several projects. Perhaps the most useful overall has been support of a patient data base which was started in the 1970s and continues to provide access to patient groups with specific diagnoses.
References
Woodhouse CRJ, Neild GH, Yu RN, Bauer S. Adult care of children from pediatric urology. Journal of Urology. 2012;187(4):1164-71.
Woodhouse CRJ, Lipshultz L, Hwang K, Mouriquand P, Creighton SM. Adult care of children from pediatric urology: part 2. Journal of Urology. 2012;188(3):717-23.
Female, Functional and Restorative Urology
The Clinical Lead for the Female, Functional and Restorative (FFR) Urology is Ms Tamsin Greenwell. She had a broad training both in general surgery, urology and paediatric urology. Since appointment in 2002, she has built the FFR Unit at UCLH from a single man unit into a department of four consultants, 4 clinical fellows, 2 CNPs and junior staff. It is now the largest, most prestigious FFR department in the UK and increasingly the world with over 10 international observers per year and the highest number of tertiary referrals in the UK.
The practice and research of the unit includes standard areas of female urology. However, there is a large sub-specialist interest in vesicovaginal and other urinary tract fistulae, female urethral diverticulum, male and female urethral stricture, complex male and female urinary incontinence and lower urinary tract reconstruction. As would be expected in such complex pelvic surgery, the unit works closely with urogynaecologists and colo-rectal surgeons.
The unit is closely involved with the MASTERS, the VERIFY, the FUTURE and the ARTISAN trials. Ms Greenwell is co-applicant on the recently awarded PURSUIT trial.
Renal Oncology
Kidney Cancer
In recent years the management and prognosis of cancer of the kidney have undergone major improvements. The more frequent use of ultra-sound to investigate abdominal symptoms has increased the number of kidney tumours, often found serendipitously, while still small. This allows earlier and less invasive treatment.
As with all cancers, earlier diagnosis improves prognosis. However, it has also identified many small kidney tumours that may never be a threat to the patient’s health, may even be benign and do not require treatment.
In the 2016 grant round, the renal group were awarded a St Peter’s Trust grant to investigate a means of identifying which renal masses do or do not need treatment. The work will be done by Dr Joana de Azevedo, Barreiros Briosa Neves, and Dr Agata Nyga, Dr MaxineTran under the supervision of Professor Mark Emberton. in the UCL/UCLH Urology, Oncology Division of Science and Interventional Science
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.
In 2019, the group were awarded funding for a PhD programme. It is planned to grow ‘organoids’ of renal cancers to test the effectiveness of anti-cancer drugs and immune modifiers.
Prostate diseases
The Prostate Research Group in UCL is going from strength to strength. It is currently led by Professor Mark Emberton with about 20 research staff. Over the last 4 years they have conducted almost 20 phase I and II clinical studies and recruited nearly 1,000 men to these trials. An achievement which places the group at the forefront of the North-East Cancer Network’s trial recruitment numbers. Their income now totals approximately £12M in active grants from various sources.
Innovative research has also continued. They are evaluating new ways of diagnosing prostate cancer using urine and blood biomarkers, multi-parametric MRI and multi-parametric ultrasound as devices that might transform the diagnostic pathway for men with a suspicion of prostate cancer or those already diagnosed with it. They have led on the development of a new image-fusion device called SmartTarget undertaken with the engineering faculty at UCL as an example of bench to bedside commercialisation.
The group received a grant in the 2016 round from St Peter’s Trust to measure changes in the levels of cell free DNA (cfDNA) and circulating tumour cells (CTCs) in the blood. Such markers could be used to stratify patients into high or low risk without an invasive biopsy of the prostate itself.
Their major project area – the minimally-invasive treatment of prostate cancer – has also seen substantial growth and they have led the field in focal therapy using high intensity focused ultrasound (HIFU) and cryotherapy with over 600 men treated focally over the last 5 years. The early and medium-term results are very encouraging and other centres are now starting to adopt it in Harlow, Southampton and Basingstoke. A wide range of other new treatments is also being assessed – such as irreversible electroporation, radio frequency ablation, magnetic nanoparticles, water vapour and injectable toxins that aim to target just the cancer tissue.
The group is also working on an assessment of the feasibility and acceptability of a new clinical trial design. More than 40,000 men are diagnosed with prostate cancer every year in the UK. There are several different treatments available but much uncertainty as to which might be best, so more evidence is needed through review of outcomes in comparable cases. Randomised controlled clinical trials are often used to compare treatments (in drug trials for example), where neither the patient nor the doctor knows which patient is receiving what. But where surgery is involved it is almost impossible to use such trials or to recruit to them. Surgeons and their patients often have strong – but sometimes misplaced – ideas of what works. It is very important to obtain unbiased information as to the best surgical procedure to employ in any given case, and the researchers therefore propose to test a new trial design which, if successful, could change the entire way randomised clinical trials are run in surgical specialties.
Much of this was achieved through the seed-corn funding provided by St Peters Trust.
Genetics of prostate cancer – Urosplice
The gene-based laboratory research programme is hosted by the St Bartholomew’s Cancer Institute and is led Dr Prabhakar Rajan. He has a talented and passionate group of scientists with expertise in cancer research and genetics, including Dr. John Foster and Dr. Anthony Anene (Post-doctoral research associates), and Ms. Becca Arkell (Research Technician). They are using cutting-edge molecular techniques to explore how genetic changes within prostate cancer cells affect the way that they behave in the human body. There is a fundamental genetic process called alternative pre-mRNA splicing, where genes are shuffled to generate multiple different proteins from a single gene. These proteins have differing functions within the cell and may contribute to prostate cancer spread to other parts of the body.
They also undertake translational prostate cancer research in patients and are attempting to identify specific molecules that will help tailor treatment thereby reducing side-effects and give treatments only to those who will respond. This would also reduce costs.
They have a productive clinical prostate cancer outcomes-based research programme and are studying outcomes for robot-assisted radical prostatectomy, and how medical comorbidities affect patient outcomes after treatment.
They have received prestigious grants from Cancer Research UK, the Royal College of Surgeons of England, Orchid and Barts Charities, and The Urology and John Black Charitable Foundations.
For further details, please see http://www.bci.qmul.ac.uk/en/staff/item/prabhakar-rajan and/or contact [email protected]
Publications:
The effect of comorbidity on prostate-cancer specific mortality: a prospective observational study. Rajan P, Sooriakumaran P, Nyberg T, Akre O, Carlsson S, Egevad L, Steineck G, Wiklund NP. J Clin Oncol. 2017; JCO2016707794 PMID: 28930493.
Oncologic outcomes after robot-assisted radical prostatectomy: a large european single-centre cohort with median 10-year follow-up. Rajan P, Hagman A, Sooriakumaran P, Nyberg T, Wallerstedt A, Adding C, Akre O, Carlsson S, Hosseini A, Olsson M, Egevad L, Wiklund F, Steineck G, Wiklund P. Eur Urol Focus. 2016; pii: S2405-4569(16)30154-7 PMID: 28753802.
Next-generation Sequencing of Advanced Prostate Cancer Treated with Androgen-deprivation Therapy. Rajan P, Sudbery IM, M. Eugenia M. Villasevil MEM, Mui E, Fleming J, Davis M, Ahmad I, Edwards J, Sansom OJ, Sims D, Ponting CP, Heger A, McMenemin RM, Pedley ID, Leung HY. Eur Urol. 2014; 66(1):32-9 PMID: 24054872.
The RNA-binding and adaptor protein Sam68 modulates signal-dependent splicing and transcriptional activity of the androgen receptor. Rajan P, Gaughan L, Dalgliesh C, El-Sherif A, Robson CN, Leung HY, Elliott DJ. J Pathol. 2008; 215(1):67-77 PMID: 18273831
