Women's Health (Research Division)

Pre-term labour, prediction and preventio of pre-eclampsia, measurement of blood pressure in pregnancy

020 7188 3639

020 7620 1227

Pre-eclampsia remains a common disorder of pregnancy, affecting 3-5% of all pregnancies and threatening the health, and indeed the lives of the mother and baby. Our group has a long standing interest in maternal endothelial function in pre-eclampsia and the role of oxidative stress the aetiology of the disease. Early research from our group was amongst the first to show clear evidence for endothelial dysfunction in women with pre-eclampsia, now considered to play a pivotal role in the maternal syndrome. We have actively pursued the hypothesis that oxidative stress, arising from placental dysfunction, and through exaggeration of the inflammatory response and endothelial dysfunction, is intimately involved in the origins of the disease.

In 1999, in a small study, we showed that antioxidants improved vascular function in women at risk of the disease, and the study showed early promise as fewer women developed pre-eclampsia. However a subsequent nationwide randomised controlled trial conducted by our unit showed no benefit of prophylactic treatment with vitamins C and E. In common with other cardiovascular diseases associated with oxidative stress it appears that antioxidants will not be able to provide an easy preventative strategy, but this does not mitigate against a role for oxidative stress, and we actively pursue research in that area. Having worked for some time in development of predictive tests for pre-eclampsia, and published patents in that area, we have recently joined the international study ‘SCOPE’ which aims to develop accurate predictive tests for pre-eclampsia, pre-term labour and fetal growth restriction. SCOPE draws upon scientific and clinical expertise from Universities across the world, and provides a unique opportunity for not only elaborating predictive tests but also through state-of-the art proteomics and bioinformatics, providing new insights into the aetiology of the three most common disorders affecting pregnant women.

Research in the unit run by Professor Andrew Shennan, is involved in a very practical problem, the accurate measurement of blood pressure in pregnant women. The last few years has seen the development of a wide range of automated instruments designed to measure blood pressure, and intended to provide replacements for the mercury sphygomanometer. Unfortunately, many have not been validated, especially for use in pregnancy. Professor Shennan’s team are accredited to validate new blood pressure measuring devices and have recently developed new devices for accurate measurement of blood pressure in the clinic, and a new, robust and inexpensive device for use in the developing world.

020 7188 3639

020 7620 1227

Urinary proteomics in the prediction and diagnosis of pre-eclampsia, prediction of pre-eclampsia in high/low risk women in pregnancy, automated protein urinalysis for hypertensive women in pregnancy

020 7188 3630

020 7620 1227

Dr Tribe's scientific research interests include ion channel function and cell signalling in smooth muscle, the physiology of parturition, contribution of inflammation and mechanical strain to the regulation of uterine smooth muscle function and gene/protein expression, the impact of obesity and maternal age on pregnancy outcome.

Clinical studies include:
- the predication, prevention and treatment of preterm labour
- improving induction and augmentation of labour
- development of new tocolytics for the treatment of preterm labour

020 7188 3635

020 7620 1227

Human embryonic stem cells, preimplantation genetic diagnosis, preimplantation genetic haplotyping

020 7188 4138

020 7620 1227

Infertility is considered to affect 10 percent of women of reproductive age in the UK, and an increasing problem as women delay childbearing and because of the high incidence of sexually transmitted diseases which impact upon fertility. Modern assisted reproduction technology offers both infertile women and men the potential to have a healthy child. In addition, ART with pre-implantation genetic diagnosis (PGD) has allowed detection in the early embryo of life threatening single gene related disorders, which through selection of unaffected embryos has enabled the delivery of healthy children to gene carrying or affected parents. The Reproductive Medicine Unit located at the Guy’s Campus comprises the Reproductive Medicine Clinic (RMC), the Assisted Conception Unit (ACU) and the centre for Pre-implantation Genetic Diagnosis (PGD). Together these provide a highly rated comprehensive fertility and reproductive medicine service with over 2000 new patients seen per annum and substantial research potential.

The focus on research is improvement in the outcome of fertility treatment, developing novel efficient techniques for PGD and providing materials for establishing stem cell lines from embryos affected by clinically relevant genetic disorders, under GMP conditions.

020 7188 8042

020 7620 1227

Integrative neuroscience, neurobiology of reproduction and sociality, nutritional influences on reproductive physiology, early life programming for obesity, Circadian biology.

020 7848 6205

020 7848 6280

Melatonin: The pineal hormone, melatonin shows a dramatic, precisely-regulated circadian rhythm of synthesis and release. It acts through specific, high affinity, G-protein-coupled cell membrane receptors to regulate circadian and seasonal physiological changes. We are involved in a collaborations with chemists at University College London and the University of Athens to design, synthesize and evaluate novel melatonin analogs. The project aims to understand the molecular basis of the recognition of melatonin, receptor activation and subtype specificity. We have developed some of the first subtype selective melatonin receptor agonists and antagonists. Novel analogues are examined in vitro, and in cell systems. In addition, in vivo effects on circadian rhythms in activity, temperature and sleep are monitored by telemetry. We are currently investigating the role of endogenous melatonin in sleep, and the mechanism of action of exogenous melatonin as a hypnotic. Melatonin analogs have recently been licensed for sleep problems and depression. Chronic sleep disturbance (often caused by desynchronised circadian rhythms) is increasingly recognised as an important risk factor for cardiovascular disease and metabolic disorders. We are interested in the effects of circadian disruption on health and have substantial experience of using radiotelemetry in small animals for chronic measurement of physiology and behaviour.
Quantitation of gene expression: Over several years the group has built expertise and state-of-the-art facilities for gene expression analysis using qPCR and has played a major role in spreading best practice in this technique in the UK through a variety of training courses attracting participants from the UK, Europe, South America and the Middle East. I am involved with a number of projects using real-time RT-PCR to quantitate steady-state levels of gene expression in various endocrine and neural cells and tissues. One of these projects in collaboration with Dr David Klein (NIH, USA) is a detailed examination of the circadian control of the expression of the genes encoding proteins (receptors, enzymes, transcription factors etc.) known to be important for the nocturnal synthesis of melatonin. Others include studies using qPCR assays to validate microarray data..
Melanopsin: Melanopsin is a novel, retinal, opsin-like protein, first identified in skin cells (melanophores) of Xenopus leavis. Recent work shows that it acts as light detector mediating the entraining action of light on the circadian clock in the SCN, and various other effects of light. We are using a Xenopus melanophore cell line, which naturally expresses melanopsin and also responds to light with a dramatic redistribution of pigment granules, as a model system to study melanopsin photo-biology, signal transduction mechanisms and function.

020 7848 6274

020 7848 6280

stress and infertility, early life programming and puberty, hot flushes

020 7848 6286

020 7848 6220

kevin.o'byrne@kcl.ac.uk

The scientific community is increasingly aware that susceptibility to disease may originate in the earliest stages of human life. Population studies world-wide have shown that individuals who are undernourished in utero are more susceptible to cardiovascular and metabolic disease in later life.

Research from Professor David Barker’s unit at Southampton University over the last 20 years has sparked a remarkable resurgence in interest into the physiology of fetal nutrition. Working in collaboration with the Southampton Unit and colleagues at Cambridge and Nottingham universities, our Unit has developed several rodent models to probe the mechanisms underlylng the developmental origins of adulthood disease. Our focus has not been on undernutrition, but on overnutrition as we have shown that a maternal diet rich in fat and calories can also lead to development of disease in the offspring. We have shown that rats and mice exposed in utero to a diet rich in fat and simple sugars develop hypertension, insulin resistance and obesity.

The observation that maternal obesity and a hypercalorific diet in rodents can ‘programme’ obesity in the developing child has generated considerable interest, not to mention concern, should it be proven that this also occurs in human pregnancy. Indeed, some observational studies from other groups working with women and their children have provided some evidence to support a similar transmission of an obesogenic trait from mother to baby.

We are now pursuing our animal models with a view to understanding the underlying mechanisms, with particular focus on the hypothesis that the maternal nutritional environment may permanently ‘rewire’ the appetite control centres of the developing hypothalamus. Unravelling the epigenetic mechanisms which ensure persistent alteration of physiological and biochemical function from the in utero and early post natal environment, through to adult life presents a terrific challenge Some insight has been gained from recent work in our group which has suggested that the mitochondrion may carry the ‘memory’ and be causative in the later development of disease.

In pregnant women we are carrying out an NIHR funded intervention study to improve pregnancy outcome . Having developed and piloted a physical activity and dietary intervention we shall carry out a large national randomised study. As well as improving pregnancy outcome we anticipate that this study will provide valuable information in regard to the developmetal origins of obesity.

020 7188 3639

020 7620 1227

Dr Taylor’s research interests include the ‘developmental programming’ effects of maternal nutrition and the hormonal environment in pregnancy on the offspring’s future cardiovascular and metabolic development. The goal of the Developmental Programming Research Group is “To understand the consequences of maternal obesity and poor nutrition in pregnancy on the future health of the child”. Specifically, the group aim to investigate the physiological processes and the cellular and molecular mechanisms whereby a baby’s exposure to an aberrant hormonal or nutritional environment in pregnancy and lactation gives rise to increased risk of obesity and associated disorders in later life. These include the ‘metabolic syndrome’, a triad of diabetes, high blood pressure and raised cholesterol in the blood. Dr Taylor has previously been the recipient of a British Heart Foundation Junior Research Fellowship and has been awarded 5 project grants in the last 5 years (3 as principal investigator) within the field of Developmental Programming. Recent publications include a recent review for Experimental Physiology on the Developmental Programming of Obesity and several related book chapters. Original articles include publications the Journal of Hypertension and the Journal of Physiology investigating the effect of maternal high fat diet in pregnancy on offspring phenotype and a recent Circulation paper provided proof of concept for the Predictive Adaptive Responses hypothesis.

020 7188 3630

020 7620 1227

The Menopause Research Unit was established at Guy’s Hospital in 1990. The main research areas have been the effect of ovarian failure on osteoporosis, endothelial function and cognition. The unit has collaborated with many other divisions due to the nature of ovarian failure and the fact that it affects so many systems. The unit has been involved in international and national multi-centre trials to investigate new hormone replacement therapies.
The latest trial is investigating women with premature ovarian failure and randomising them to HRT or OCP. Main outcome measure is bone density.

Having recently established Guy's and St Thomas' as an endometriosis centre with the colorectal surgeons the potential is there to commence research into women who have severe endometriosis.

Being the lead for Reproductive and Sexual Health taching within King's College educational research has centred around the presence of medical students in the gynaecology clinic, chaperones, the introduction of the Gynaecology Teaching Associate Programme and more recently Breast Teaching Associates.

020 7188 3631

020 7620 1227

020 7848 6286

020 7848 6220

kevin.o'byrne@kcl.ac.uk

Lower urinary tract dysfunction and genital prolapse affect over 20% of the adult population. Prolapse and lower urinary tract problems cause significant psychological and quality of life impairment.  Current treatments and access to treatment have significant scope for improvement and real world evaluation outside the context of controlled clinical trials.

Urogynaecology is currently carried out on two sites within King’s Heath Partners, Kings College Hospital and St Thomas’ Hospital. The Urogynaecology Unit at Kings College Hospital NHS Foundation Trust is the largest tertiary referral centre in London and has an established National and International reputation for active clinical research, clinical practice, teaching and training. The Unit currently employs three full time Consultant Urogynaecologists (Cardozo, Robinson, Bidmead).

Current research funding is from industry grants, competitive grants and private sponsorship. Grants and funding pay for the salaries and overheads of research fellows and specialist additional equipment. Whilst individual grants are not large they have covered the costs of highly successful and innovative research for the last twenty five years.