Research achievements

Targeted cancer therapies

Great Ormond Street Hospital has a long history of developing new and life-saving treatments for children with cancer. Though survival rates continue to improve, a pressing challenge remains to ensure children are not overtreated.

Professor Kathy Pritchard-Jones is researching increasingly personalised treatments to give children the best chance of a long-term cure without undue side effects.

"When I gained my PhD almost 20 years ago, we were just beginning to scratch the surface of understanding the genetic changes which take place inside a cancer cell's DNA, and how these could predict a patient's response to treatment.

"We are now in the era of 'molecular medicine', which means that new anti-cancer therapies can be much more specific and with fewer side effects.

"However, we still need to do clinical research if children with cancer are to reap the full benefits of these new medicines. We have to ensure we offer new drugs in a safe and controlled way, especially to children with the highest risk tumours

"Having virtually every type of therapy required under one roof makes working here very special for staff, and far less stressful for patients and their families. One of the pleasures of my job is to be able to reassure most parents that we have treatments that can cure their child."

Refusing to be beaten

Cilia are tiny, rhythmically beating hairs that move biological materials around the body and clean out the body's airways to prevent infection. Named after the Greek word for 'eyelash', they are more than a thousand times smaller than an eyelash and can be found throughout the body. There are also non-beating cilia which are essential for cells to sense the world around them.

Dr Hannah Mitchison's research aims to help children whose cilia do not function properly, and for whom a cure remains an elusive goal.

"The fast-moving field of human disease genetics was an exciting place to be during my first postdoctoral research period. I was part of an international team effort that identified the gene responsible for Batten disease. This kick-started a new understanding of this family of at least 10 fatal neurodegenerative disorders.

"Gene identification has led to novel hypotheses about the causes of these diseases and has allowed us to progress with genetic tests and clinical trials of new therapies.

"For the last decade, I have been increasingly involved in discovering the molecular basis of cilia-based disorders. Recently, I helped to found the Ciliopathy Alliance, which provides a collective voice for families, scientists and clinicians, to support and raise awareness of these diseases

"I hope our molecular genetics approach will crack open what causes these ciliopathy disorders, just as it has for Batten disease and some of the other ciliopathies."

Let the right sun in

Vitamin D has long been labelled 'the sunshine vitamin' due to the way it is synthesised in our skin. But, although it is now readily available as a health supplement and is also thought to be 'good for our bones', we are still some way from fully understanding its modes of action.

Dr Elina Hyppönen's research seeks to bring Vitamin D out of the shadows and into the sphere of public health debates.

"I became interested in epidemiology and public health because to me, it made more sense to focus on prevention where possible, than to strive to alter things once the damage had already been done.

"It was the findings from my PhD thesis which directed my subsequent research interests. I observed a strong dose-response association between infant Vitamin D supplementation and the risk of Type I diabetes in children. This was exciting as, until then, Vitamin D had been considered something that is mainly needed for bone health. Yet here we were showing evidence for possibly important influences on an autoimmune disease.

"The University College London (UCL) Institute of Child Health (ICH) has provided a very stimulating research environment, and I've received further support by being given the Department of Health Public Health Career Scientist Award in 2005. Currently, I lead a large international collaboration of studies with the aim of disentangling the causal from the coincidental in the proposed health effects for Vitamin D."

Relearning how to learn

"What does it mean to be me?" is a question more likely to be asked by philosophers than scientists. But if your brain is so damaged that it can't create long-lasting memories, making sense of your own identity becomes an enormous challenge.

Professor Faraneh Vargha-Khadem is developing ways to support children with these severe and chronic forms of memory disorder, known as developmental amnesia.

"I came to ICH in 1983 from the Montreal Children's Hospital McGill University,where I had been researching how the mind compensates for damage to just one side of the brain, and how this impacts a child's speech and language.

"Fascinated by the hallmark research of Margaret Kennard on the adaptability of the motor system, I hoped to explore how focal brain lesions affected children's higher cognitive function. A project grant from the Medical Research Council enabled me to establish a research group and, together with my colleagues, we started our first set of studies in the emerging field of developmental cognitive neuroscience.

"As a clinical neuroscientist, I have been fortunate both to have access to unique patient groups, and to establish interdisciplinary collaborations with imaging scientists and neurologists,. This has enabled me to conduct translational research in a highly stimulating environment. I hope that our research will ultimately relieve patients of the burden brain injury can have on their lives."

Kidney cures from cancer drugs to citrus fruit

Great Ormond Street Hospital is the UK's largest centre for children with kidney problems. Dr David Long is a scientist, pioneering research to discover the mechanisms of kidney disease and develop new treatments. From examining thin sections of kidney tissue right through to probing the finest microscopic structures of the kidney's delicate filtering units, the research team are revealing new insights into preventing and treating childhood kidney disease.

"My enthusiasm for kidney research started during my PhD, when I investigated normal kidney development and how this goes wrong in kidney disease.

"Professor Adrian Woolf and I discovered that proteins called angiopoietins play a key role in the initiation and progression of kidney disease by controlling growth of kidney blood vessels. These studies led to the award of a Senior Fellowship from Kidney Research UK to build upon this finding with my own research team.

"The challenge for the future is to convert our basic laboratory findings into new treatments. The close ties between Great Ormond Street Hospital and the Nephro-urology Unit at ICH provide an ideal environment for this, and I am now studying angiopoietins in children with chronic kidney disease in collaboration with Dr Rukshana Shroff and Dr Lesley Rees. This is particularly important because there is currently no therapy that reliably corrects severe kidney problems and so many patients need either life-long dialysis or transplantation. We hope to develop drugs to modify angiopoietins as a way of treating both children and adults with renal disease."

Personalising children's treatments for arthritis

As many as one in 1,000 children in the United Kingdom (UK) are affected by arthritis and looking after these children is a complex issue. Professor Lucy Wedderburn's research aims to balance the dosage of drugs to reduce pain and swelling with minimising the side effects of current treatments which can be debilitating for children with arthritis.

"In children, the immune system has to frequently fight off new infections without causing reactions against the body's own cells or tissues. During my clinical training I realised that not much is really known about how the immune system controls the balance between fighting infection yet staying 'tolerant' to our own body, and I have worked in this area ever since.

"My lab group focuses on what causes and drives arthritis and myositis, and in particular, the childhood immune system's role in remission, when it is achieved, and how we can predict a child's response to treatment.

"Our future goal of 'personalised medicine', where each treatment plan will be based on an evidence-based set of factors that we can measure (genes or other biological molecules) as well as family factors, will allow us to use the available treatments in a more targeted way. I hope this will lead to early remission in a far greater number of our patients."