Translational Medicine

Artemisinins are very poweful tools in the treatment of malaria, and the emerging loss of their activity has the potential to create a major public health problem. MALARIA TREATMENT Dr Charlie Woodrow is based at MORU in Bangkok, Thailand, where he coordinates clinical and laboratory studies on resistance to artemisinins. Bringing together diverse datasets of clinical, in vitro and molecular data has helped better understand the emerging resistance, particularly in Myanmar.

Asthma and COPD (chronic obstructive pulmonary disease) are common conditions that affect the lives of many people. Dr Mona Bafadhel studies the pathophysiology of COPD (chronic obstructive pulmonary disease). There are broadly two inflammatory phenotypes of COPD that are clinically indistinguishable but have different treatment responses. Dr Bafadhel is working on the development of novel therapeutic strategies for COPD, particularly to treat the regular periods of worsened symptoms that patients experience.

Alteration of gene expression is fundamental to many diseases. A better understanding of how epigenetic proteins affect diseases provides a starting point for therapy development and the discovery of new drug. Professor Paul Brennan research focusses on epigenetics: the mechanisms that control gene expression. He studies how chemical probes interfere with epigenetic enyzmes that can be targeted to treat various diseases. Epigenetics combined with disease biology will ultimately accelerate drug discovery.

A missing step in a metabolic pathway leads to the build-up of toxic compounds, and the lack of materials essential for normal function. Professor Wyatt Yue explores how genetic defects lead to disease at the molecular level, by determining 3D structures and biochemical properties of enzymes and protein complexes linked to congenital genetic errors. Professor Yue works closely with clinicians and paediatricians to decipher the underlying genetic, biochemical and cellular mechanisms of these diseases. His long-term aim is to help design novel therapeutic approaches for metabolic diseases.

Too high a dose can result in toxicity and side-effects, too low a dose can cause the illness to come back and at worse develop resistance. Professor Joel Tarning is Head of Clinical Pharmacology in our MORU Unit in Bangkok, Thailand. He's working towards drug dose-optimisation using novel pharmacometric modelling approaches. He is particularly interested in antimalarial treatments for children and pregnant women.

Video microscopy aims to improve target discovery and drug development and to do so generates large volumes of data. Professor Jens Rittscher has a joint appointment between the Ludwig Institute for Cancer Research, the Target Discovery Institute and the Department of Engineering Science. His research aims to enhance our understanding of complex biological processes through the analysis of image data acquired at the microscopic scale.

Dr Sebastian Nijman develops new approaches to study signalling networks in cancer cells and uncover specific weaknesses, particularly in breast and lung cancer. This can be used to develop more effective drugs and to better guide treatment decisions. In the context of cancer, genetic diversity means that we respond differently to various treatments. Pharmacogenomics sits at the intersection between genetics and drugs. Better understanding of the genetic landscape of cancer and the recent increase of targeted drugs allow us to better match patients with the best treatments, improving care.

Dr Trudie Lang tells us how the Global Health Network facilitates collaboration and resource sharing. Clinical trials establish the evidence base for prevention and treatment of disease and are critically important in the field of Global Health. Dr Trudie Lang leads the Global Health Clinical Trials group, which aims to promote and improve the conduct of non-commercial clinical research across all diseases in resource-poor settings.

Professor Arjen Dondorp tells us about his work on severe malaria and the development of new therapies. Current malaria therapies using artesunate aim to kill malaria parasites before they mature. Such medications have high success rates but need to be developed further. Based in Bangkok, Thailand, Professor Arjen Dondorp works on the pathophysiology and treatments of severe malaria, antimalarial drug resistance, and improvements in intensive care practice within developing countries.

Professor Kevin Marsh tells us about his research on Tropical Medicine in Kenya. Professor Kevin Marsh has a broad research interest in child health in the tropics, with a particular focus on the immune epidemiology of malaria. Malaria remains a major world health problem, particularly among children in Africa. Based in Kenya, Professor Marsh is working on preventing and curing malaria in Africa. Professor Marsh is director of the KEMRI Wellcome Programme in Kenya; he also coordinates the malaria immunology group within the programme.

Professor Nick White talks about the future of artemisinin and other drug therapies for malaria. Malaria kills more than half a million people every year. Following a number of groundbreaking clinical trials, Professor Nick White and his Thailand team successfully demonstrated the effectiveness of artemisinin drug therapy for malaria in adults, children and infants. He also pioneered artemisinin combination therapy, the first-line treatment for malaria worldwide.

Microbiology in Thailand Acurately diagnosing infections is particularly challenging in tropical environments. Researchers at the Mahidol Oxford Tropical Medicine Research Unit (MORU) are working to develop effective and practical means of diagnosing and treating malaria and other neglected tropical diseases, such as dengue fever. The development of rapid tests for dengue, similar to pregnancy tests, allow rapid and acurate diagnostics in the field.

Infectious diseases in South East Asia The Mahidol Oxford Tropical Medicine Research Unit (MORU) is a collaboration between the University of Oxford and Mahidol University, and was established with the Wellcome Trust in 1979. MORU aims to fight the infectious tropical diseases affecting rural communities in Asia and elsewhere in the developing world. MORU's malaria research aims to directly improve the treatment of the disease globally. It's researchers focus on the treatment of severe malaria, the spread of antimalarial drug resistance, and the pathophysiology of falciparum and vivax malaria. These studies are used to formulate novel adjuvant therapies, and have been translated into recommendations for the use of artemisinin based combination therapies.

Daniel Paris: Rickettsial Disease Rickettsial diseases such as scrub typhus are important causes of fever in southeast Asia especially in rural communities. Discovered quite recently and not big killers, these diseases are among the most under-reported and under-diagnosed illnesses that are both treatable and preventable. Rickettsial studies at he Mahidol Oxford Tropical Medicine Research Unit (MORU) focus on the epidemiology and incidence of the disease using hospital-based fever studies in Thailand and Laos. Our research unit has developed highly improved acute diagnosis of rickettsial illness. MORU also has ongoing studies to determine the pathophysiological mechanisms of scrub typhus infection.

Professor Peter Donnelly tells us how genetics helps us to understand common diseases and develop new drugs. Understanding which variations in our DNA affect susceptibility to diseases can provide new insights into the disease process and lead to new treatments. Professor Peter Donnelly leads large collaborative human genetic studies, and his group develops and applies statistical methods to extract maximal information from the large datasets generated by genomic studies.

Dr Najib Rahman talks about his research on respiratory medicine. The Pleura are thin membranes that cover the surface of the lungs. Dr Najib Rahman specialises in areas of respiratory medicine including pleural disease and the conduct and analysis of respiratory trials. Dr Rahman is currently conducting clinical studies in malignant and infectious pleural disease, and is Clinical Director of the Oxford Respiratory Trials Unit.

Professor Stefan Knapp tells us how the development of chemical probes helps us to find new drugs. The role of proteins in cellular signalling and disease is best studied through the development of highly specific chemical inhibitors, which can serve as a tool molecule for functional studies. Professor Stefan Knapp works to determine the structure of protein molecules to understand their regulation and to aid the design of selective inhibitors that can be developed further into efficient drugs

Every psychiatric disorder has a genetic contribution. Although anxiety and depression are very common diseases, current treatments are not very good. A better understanding of the contribution of genetic variants might help us better diagnose as well as develop new therapies.

Dr Sumi Biswas talks about the development of a vaccine aimed at the mosquito stage of the malaria parasite cycle. Malaria transmission-blocking vaccines aim to induce immunity against the parasites that infect mosquitoes. Such vaccines will prevent malaria transmission on a wider scale, focusing on the community rather than the individual. Dr Sumi Biswas is working on the development of transmission-blocking vaccines to prevent the spread of malaria.

Dr Liz Carpenter talks about her research on membrane proteins and drug development. Membrane proteins are the gateways to our cells - with nutrients, waste products, and even DNA and proteins entering and leaving cells via these tightly controlled proteins. Drugs often target membrane proteins; therefore, understanding their molecular structure helps us design better drugs. Dr Liz Carpenter uses X-ray crystallography to solve membrane protein structures. This information is then used to improve treatments for heart disease and neurological diseases.

Professor Fiona Powrie talks about the importance of our guts, and her research in gastroenterology.

Dr Simon Travis tells us how clinical trials bring tomorrows treatments to patients today. Before translating basic research into the clinic it is important first to undergo clinical trials in order to identify safe treatments and therapies for disease. Led by Dr Simon Travis the Gastroenterology Clinical Trials Facility at Oxford University works to translate basic research into clinical trials of novel therapies for gastrointestinal and liver diseases.

Dr John Frater talks about his research into finding a cure for HIV. It is increasingly apparent that highly active antiretroviral therapy (HAART) may not be the long-term solution to the management of HIV infection, and that other avenues need to be explored. As a result of various recent cases, the idea of eradicating HIV altogether is becoming less unimaginable to some scientists.

Professor Lars Fugger talks about his research on multiple sclerosis. Multiple Sclerosis (MS) is a disease that affects the brain and the central nervous system. While there were no therapies for MS 20 years ago, there are now 8 registered drugs for the disease. Professor Lars Fugger focuses on translational studies in multiple sclerosis and uses a multidisciplinary approach; his group consists of both basic scientists and clinicians. Professor Fugger is seeking to understand the molecular basis for the MHC association in MS and how MHC genes interact with environmental factors such as viruses.

Dr Holm Uhlig talks about the role of the immune system in our gastrointestinal tract. The gastrointestinal tract is home to more bacteria than there are cells in our body. In order to stay healthy, our immune system must maintain a strong and effective response towards these bacteria. Dr Holm Uhlig is based at the Translational Gastroenterology Unit and studies defects in the immune response and regulation leading to immunopathology. Dr Uhlig is predominately interested in children with inflammatory bowel disease, and aims to understand the complex puzzle of molecular mechanisms involved.

Professor Richard Cornall tells us about his research on autoimmunity. Autoimmunity occurs when the immune system, which is normally designed to attack pathogens, ends up attacking the body. This can lead to a number of diseases such as diabetes and rheumatoid arthritis. Professor Richard Cornall aims to understand the causes of autoimmune disease, and also how people differ in their inherited susceptibility, and why these differences are sustained in human populations by natural selection.

Dr Simon Draper tells us about his progress in malaria vaccine research. Dr Simon Draper's research interests include studies of vaccine induced malaria immunity. His group focuses on translational medicine. They will take their most promising vaccine candidates and manufacture them as clinical grade material. The next step is proof of concept clinical trials in healthy volunteers.

Dr Katharine Owen talks about the different types of diabetes in young adults. There are more forms of diabetes than the commonly known type 1 and type 2. Correct diagnosis of the different forms of diabetes is difficult because of the overlap of symptoms. The implications of incorrect diagnosis are huge, as some forms of diabetes respond better to certain treatments than others. Dr Katherine Owen investigates the different characteristics of monogenic diabetes with the aim of creating systematic diagnostics, and implementing that in clinical care. The ultimate aim is to promote personalised medicine for everybody with diabetes.

Professor Mark McCarthy tells us how genomics helps us understand diabetes. Diabetes is a major challenge for global healthcare, with social, health and economic costs projected to exceed trillions of dollars over the next 50 years. Professor Mark McCarthy, the Robert Turner Professor of Diabetes, leads a multidisciplinary research team including clinicians, nurses and lab-based research staff. Professor McCarthy's research focusses on translating gene identification and genetic information into advances in the functional understanding, and clinical management of this disease.

Dr Arturo Reyes-Sandoval tells us about his research on a vaccine against Plasmodium vivax. Dr Reyes Sandoval aims to develop a novel malaria vaccine against Plasmodium vivax, one of the four malaria parasites that affect humans. P. vivax is found in Africa, Asia, Latin America and the Western Pacific. 40 percent of the world's population is exposed to the disease that is responsible for around 130 to 350 million clinical cases every year.

Colin Baigent, Professor of Epidemiology, Clinical Trial Service Unit, Oxford, talks about why the drug Statin saves lives.

Professor Tomas Hanke tells us about his research on HIV vaccine development. The long term aim for Professor Tomáš Hanke is to develop a safe, effective and accessible HIV-1 vaccine. His group tests novel ideas and vaccine strategies, and focusses on a safe but rapid translation of the most promising laboratory results to phase I/II clinical trials in human volunteers.

Professor Stephen Gough talks about the development of personalised diabetes treatment. An estimated 500 million people worldwide will be affected by diabetes within the next fifteen years. Professor Stephen Gough believes that you cannot give every patient affected by diabetes the same treatment, since people react differently to treatments. Professor Gough looks at the reasons behind differences in the way that people react to diabetes treatments, in order to improve care and reduce the health and economic costs associated with the disease. Professor Gough aims to provide the right treatment to the right person at the right time in their disease for optimum results.

Professor Gil McVean tells us how statistical genetics helps us understand and treat disease. Genomic technology and statistical analysis of the genome is a powerful tool in understanding disease. Prof Gil McVean is the Head of Bioinformatics and Statistical Genetics at the Wellcome Trust Centre for Human Genetics. Professor McVean's research covers several areas in the analysis of genetic variation. Combining the development of methods for analysing high throughput sequencing data, theoretical work, and empirical analysis, this research may lead to genetic diagnosis and targeted treatments for disease.

Dr Leanne Hodson talks about her research on liver fat metabolism. Understanding liver fat metabolism is extremely important, as the health risks associated with fatty liver disease can include diabetes, heart disease and liver cancer. Fatty liver disease is defined as having over 5 percent liver fat, and a 'silent disease' as many people are not diagnosed. Dr Leanne Hodson is working on finding targets for new medications, which will help lower the risk of accumulating liver fat leading to fatty liver disease.

Dr Barbara Fielding talks about her research on the metabolism of fatty acids. Obesity continues to have a major impact on health care services in the UK. Dr Barbara Fielding believes that nutritional advice should be based on a thorough understanding of metabolic responses to food ingestion, and that it is important to investigate the metabolism of dietary fat after both single and multiple meals. By tracing fat atoms from meals into the blood, Dr Barbara Fielding's research into individual metabolic responses to food ingestion may lead to targeted, customised, and more effective nutritional advice for obese and overweight patients.

The largest trial investigating the benefits of cholesterol lowering in kidney patients. The Study of Heart and Renal Protection (SHARP) concluded that around a quarter of all heart attacks, strokes, and operations to open blocked arteries could be avoided in people with chronic kidney disease by using the combination of ezetimibe and simvastatin to lower blood cholesterol levels.

Dr Anna Gloyn talks about her research on the genetics of diabetes. An estimated 366 million people worldwide now suffer from diabetes and the global epidemic is getting worse. Dr Anna Gloyn uses genetic variants in humans as tools to identify critical regulatory pathways for insulin secretion and action. Current research projects are focused on the translation of genetic association signals for type 2 diabetes and glycaemic traits into molecular mechanisms for diabetes and clinically useful tools. Understanding how genes relate to types of diabetes will enable better diagnosis and treatment for patients.

Professor Sarah Rowland-Jones tells us about her work on HIV with children in Africa. Prof. Sarah Rowland-Jones' work mainly focuses on anti-viral immunity, and in particular how immune responses modify the outcome of HIV infection. Her research aims to contribute to the design of vaccines and immunotherapies against HIV infection, including HIV-2 infection, in developing countries where an effective vaccine is desperately needed.

Professor Patrik Rorsman talks about diabetes and how beta cells within the pancreas control insulin secretion. While the lifestyle causes of type-2 diabetes are now known, the molecular details of the disease remain unclear. Professor Patrik Rorsman is researching the processes that control insulin secretion and determine defects associated with clinical diabetes. Professor Rorsman has been at the forefront of research on hormone-secreting cells in the pancreas for more than 20 years, work that is highly relevant to understanding the causes and treatment of type-2 diabetes. This research may lead to new diabetes medicines, and improved beta cells for transplantation.

Dr Lucy Dorrell tells us how our immune system controls HIV and how we can live with this virus. The aim of Dr Lucy Dorrells' research is to develop immunotherapy to reduce the dependence of those infected with HIV-1 on their current treatment - antiretroviral therapy (ART). This is because 9 million of the estimated 33 million people living with HIV/AIDS today are not able to access the ARTs which they are in immediate need of.

Dr Dianne Newbury talks about the contribution of genetics to specific language impairment. Specific Language Impairment (SLI) is a complex genetic disorder in the development of language. Dr Dianne Newbury is looking for the genes that predispose to SLI. Two regions, located on chromosomes 16 and 19, are linked with this disorder. Interactions between several normal genetic variants and environmental factors make certain individuals more vulnerable to language problems. A better understanding of these underlying biological pathways will lead to the development of more accurate identification systems and better therapies.

Dr Seph Borrow tells us how her research on HIV Immunology helps design better vaccines. There is an urgent need for vaccines to combat persistent infections like HIV. Dr Seph Borrow is studying factors affecting virus control by HIV-specific CD8+ T cells, to inform the design of T cell-based HIV vaccines. She is also exploring the possibility of harnessing innate immune responses to combat HIV.

Dr Silvia Paracchini talks about the influence of genetics in dyslexia. Dyslexia is a reading impairment that effects up to 10% of children. Dr Silvia Paracchini aims to identify the genetic components of dyslexia to better understand its underlying biology. Working to uncover the biological mechanisms involved in human cognition, Dr Paracchini is looking for connections between dyslexia and other cognitive disorders such as Specific Language Impairment or Attention Deficit Hyperactivity Disorder. Dr Paracchini is looking for possible common genes for these clinically distinct disorders.

Professor Sir Andrew McMichael tells us about recent developments in the search for a vaccine against HIV. Prof. Sir Andrew McMichael is working on human immunology and vaccines, first looking at flu virus and now HIV. His current lines of research include analysing early molecular events in HIV infection, T cell immune response to HIV and the use of vaccination to control HIV infection.

Professor Fredrik Karpe explores the links between obesity and diabetes. Obesity is the single most important factor for the current increase in diabetes. Professor Fredrik Karpe is using integrative physiological and genomic approaches to study lipid and carbohydrate metabolism, to find out more about this damaging problem. Professor Karpe is investigating the links between obesity, insulin resistance, type-2 diabetes and cardiovascular disease. Professor Karpe initiated the Oxford Biobank for prospective genetic epidemiological research.

Dr Benedikt Kessler tells us how proteomics helps find biomarkers. In most living organisms, the ubiquitin-proteasome system is responsible for the degradation of proteins, either because they're damaged or they reach the end of their life span. Ubiquitin marks a protein for elimination. Alterations in this process are responsible for many human diseases. Dr Benedikt Kessler studies the role of deubiquitylating enzymes that remove ubiquitin from substrate proteins.

Professor Paul Bowness tells us about his work on spondyloarthritis. Professor Paul Bowness works on Ankylosing Spondylitis, the commonest form of spondyloarthritis. This rheumatic disease is caused by an overacting immune system. It has a major genetic component: at least five to ten genes are known to contribute the disease, with HLA-B27 being by far the most important. Professor Bowness is investigating interactions between these genes and the immune system, for both healthy people and patients with arthritis, to better understand Ankylosing Spondylitis and how to manage it.

Dr Cecilia Lindgren explores the links between obesity and genetics. Obesity and its consequences are major and growing challenges for health care providers worldwide. While lifestyle is a contributor, over 30 genes associated with body mass index have also been identified. Dr Cecilia Lindgren uses genetic and genomic approaches to better understand the underlying mechanisms and pathways involved in the regulation of overall energy balance, to establish improved therapies and preventive measures.

Professor Chas Bountra explains how new drugs can offer novel treatments for neurodegenerative and gastrointestinal diseases, as well as pain disorders. Professor Chas Bountra is interested in identifying and validating target proteins for drug discovery. Various technologies and strategies have allowed him to progress promising clinical candidates into Phase I, II, III studies, and to market. Drug candidates are first selected by screening compounds capable of binding to a target protein. Those compounds are then tested in various assay systems, healthy volunteers and finally in patients. Academic research excels at defining good target proteins. Pharmaceutical companies then facilitate the transition from basic research to clinical trials, producing new therapies for patients.