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.

Identifying and addressing ethical issues are key to the success of any clinical trials, particularly when working with vulnerable populations. Dr Phaik Yeong Cheah leads the Department of Bioethics & Engagement at the Mahidol Oxford Tropical Medicine Research Unit (MORU) in Thailand. She is particularly interested in ethical issues in community engagement, data sharing, consent and assent in paediatric research.

In settings with high level of poverty and over-stretched health services, researchers have even greater responsibilities to the communities and study participants. SOCIAL AND BEHAVIOURAL RESEARCH A social scientist and public health researcher based in Kenya, Professor Vicki Marsh aims to understand and strenghten policies based on social and ethical aspects of international collaborations. Improving communications between researchers and the patients and local communities is not only ethically important; it can also lead to better research.

Melanoma or skin cancer is one of the fastest rising cancer types. When identified early, melanoma is relatively easy to cure, but once it starts to metastasise, it becomes very difficult to treat. DEREGULATION OF TRANSCRIPTION The interface between signal transduction and transcription regulation coordinates gene expression. Deregulation of transcription is a key factor in cancer. Professor Colin Goding studies how a precise programme of transcription regulation is achieved, particularly in the transition between normal and cancer stem cells, and the parallels with normal stem cell populations.

Transcription is a tightly regulated process, where chemical modifications initiate the duplication of genetic material. This epigenetic process is often dysregulated in cancer, but it can be targeted with small molecule inhibitors. EPIGENETIC SIGNALLING Professor Panagis Filippakopoulos is interested in the molecular mechanisms of transcription, where the formation of non-covalent protein complexes is mediated by post-translational modifications. Dysfunction in this epigenetic signalling process is linked to disease, particularly cancer.

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.

Economics and health are interlinked in many ways, as seen in the vicious cycle between poverty and ill health. Dr Yoel Lubell leads the economic team at the MORU Mathematical and Economic Modelling Group, based in Bangkok, Thailand. His research focuses on the evaluation of diagnostics, treatments and vaccines for infectious diseases, with the aim of providing guidance on malaria elimination and control of artemisinin resistance in the Mekong region.

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.

Dr Christiane Dolecek speaks about the research on enteric fever she conducted in Vietman and Nepal. Dr Christiane Dolecek's clinical research focuses on tropical diseases, in particular enteric fever and malaria. She has led enteric fever clinical trials in Vietnam and Nepal with the aim to systematically assess the current WHO recommendations as well as new treatment options.

Professor Peter Horby is Senior Clinical Research Fellow. His research focusses on epidemic diseases such as Ebola and bird flu, and crosses the disciplines of basic science, medical science and public health. Influenza, SARS & Ebola Research on emerging infectious diseases can only be conducted during outbreaks. Although virology has improved, a well calibrated and effective public health response is often lacking. Epidemiological and clinical research as well as mathematical modelling will give us answers during the epidemics and help us provide better diagnostics and better treatments.

Dr Gareth Bond, Associate Member of the Ludwig Institute for Cancer Research, studies the influence of genetic variants on the origins, progression and treatment of human cancer. SNP - single nucleotide polymorphisms There is great heterogeneity between individuals in their risk of developing cancer, disease progression and responses to therapy. Specific single nucleotide polymorphisms (SNPs) are associated with human cancers. They have the potential to help us identify individuals more at risk of developing cancer, and better target preventative or therapeutic strategies.

Dr Jenny Taylor is the Programme Director for the Genomic Medicine Theme, Wellcome Trust Centre for Human Genetics. Her research bridges the gap between genetics research and the use of its discoveries in diagnosis or treatment of medical conditions. Clinical diagnoses can be broad descriptions, but today's test results can help better understand the condition as well as target treatment. Cancer is a good example in which personalised medicine can help decide which molecular targeted therapy is most appropriate.

Identifying genes that increase the risk of bowel or other cancers allows us to offer preventative measures, such as removing tumours at an early stage. A better understanding of how and why cancers grow also helps develop improved treatments. Ian Tomlinson, Professor of Molecular and Population Genetics at the Wellcome Trust for Human Genetics, works on the identification of genes that predispose to colorectal and other cancers. His research focuses on the relative importance of selection and genomic instability.

Cancer research now generates huge amounts of data, and sophisticated computational tools are needed to answer biological questions. Making sense of this variability at molecular level will help us better tailor treatments to individual cancer patients. Dr Benjamin Schuster-Böckler heads the computational group at the Ludwig Institute for Cancer Research. His work has demonstrated that epigenetic modifications influence the mutational landscape in cancer cells. He studies the effects of DNA-binding proteins on transcription factors, with the aim to understand the regulation (and mis-regulation) of the transcription of important oncogenes and tumour suppressors.

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.

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 Townsend tells us about lessons to be drawn from the history of immunology in Oxford, from 1979 onwards, until his current research on active and passive immunity to influenza. All these developments happened in Oxford because the atmosphere was right, open, researchers were encouraged to explore, and there was an enthusiasm in a great environment. Experiments and discoveries were made possible by the very open attitude of the supervisors at the time, telling their team that they they could do anything they wanted.

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 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 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.

Professor Chris O'Callaghan tells us about the role of our immune system in vascular disease. The accumulation of fat in the arteries, such as cholesterol, can cause a thickening of the artery wall known as atherosclerosis. Professor Chris O'Callaghan is researching the role of the innate immune system in atherosclerosis to better understand immune responses to vascular disease. This may lead to improved treatments.

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 Jonathan Flint talks about his research on psychiatric genetics. It is now known that genetic variants can form the basis of psychiatric disorders, such as depression and anxiety. Professor Jonathan Flint is investigating the genetics behind psychiatric disorders, in particular the origins of stress-related conditions, such as anxiety and depression, for which we have relatively ineffective treatments.

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

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.

Dr Alexander Finlayson tells us how MedicineAfrica aims to bring healthcare professionals around the world in a global expert network. Disparity in healthcare between the developed and developing world is a major global health problem. MedicineAfrica, an online health facility, aims to connect doctors and healthcare professionals in Africa to clinical support teams around the world. Dr Alexamder Finlayson established MedicineAfrica in 2008, and is now working to develop this platform for future users, such as medical students, doctors and nurses, in other countries including Palestine and India.

Professor Kay Grunewald tells us how structural cell biology can help us understand virus infection. Cells constitute the smallest autonomous units of life. The tightly regulated structural and functional organisation is currently only rudimentary understood. Professor Kay Grünewald uses electron cryotomography in combination with other techniques to analyse virus' 'life cycle' in situ, which requires an understanding of its transient structures at the molecular level. Imaging techniques allow us to understand the communication between the virus and the components of the cell it is infecting, which can ultimately help to treat infectious diseases.

Dr Christian Eggeling tells us how new imaging methods help us understand immunology at the molecular level. To study complex biological and immunological systems, such as living cells, scientists rely on highly sensitive and non-invasive analysis techniques. Super-resolution optical microscopy allows us to study immunological processes on the molecular level. We can get new insights into how our body reacts to viral or bacterial attacks. Dr Christian Eggeling's research focuses on the application and development of superior, ultra-sensitive, live-cell fluorescence microscopy techniques. This has the potential to help us design new drugs and developing new ways of treating diseases.

Professor David Jackson tells us about the role of the lymphatic system in immunity and cancer. The lymphatic system is a network of vessels collecting the fluids leaked from the blood vasculature. Its filtering function makes it an ideal compartment for the immune system. It is also a pipeline for metastasizing tumour cells to spread to distant tissues. Professor David Jackson studies how leukocytes and tumour cells enter the lymphatic vessels from the surrounding tissues. Professor Jackson's research has the potential to help us better control the spread of tumours, block unwanted immune responses in autoimmune diseases, block tissue rejection and make vaccines more effective.

Professor Graham Ogg talks about the role of our skin as a barrier against infection. Skin frequently represents the first point of contact with pathogens and allergens, but there is still very little known about the role of the surface immune system in fighting unwanted invaders. Barrier dysfunction can lead to the development of eczema. Understanding these mechanisms can help us develop new treatments targeting the skin, as well as the inflammatory response. Dr Graham Ogg aims to understand the role of skin immune responses by studying common skin diseases and infections.

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.

Professor Vincenzo Cerundolo tells us how research in immunology leads to the development of new cancer treatments. Immunotherapy stimulates the bodys immune system and can be a powerful treatment for cancer. With the aim of developing better treatment strategies for cancer patients, Professor Vincenzo Cerundolo is working to gain a better understanding of the cell-to-cell interplay required for optimal expansion and activation of tumour-specific T cell populations.

Professor Xin Lu talks about the links between cancer and regenerative medicine. Professor Xin Lu is the Director of the Oxford branch of the Ludwig Institute for Cancer Research. Her lab works toward identifying molecular mechanisms that suppress tumour growth and metastasis and focuses on understanding the factors that lead to uncontrollable cell growth.

Dr Jan Rehwinkel talks about the role of our innate immune system in our fight against flu virus. Dr Jan Rehwinkel and his group study the bodys immune reaction to viruses such as flu and HIV 1 which affect millions of people worldwide. The aim is to impact on the management of infectious diseases and the development of vaccinations. This work also has an impact on auto-immune diseases such as Lupus.

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 Sarah Gilbert talks about her work on viral vectored vaccines. Professor Sarah Gilbert has been making and testing vaccines designed to induce T cell responses for ten years, chiefly using antigens from malaria and influenza. Based at the Jenner Institute, several of the vaccines developed in Professor Gilberts laboratory have progressed into Clinical Trials.

Professor Lars Fugger talks about his research on multiple sclerosis. Professor Lars Fugger focuses on translational studies in multiple sclerosis and uses a multidisciplinary approach. He is seeking to understand the molecular basis for the MHC association in MS and how MHC genes interact with environmental factors such as viruses. Professor Fuggers group consists of both basic scientists and clinicians.

Dr Raghib Ali talks about INDOX, the cancer research network in India. Dr Raghib Ali is the Director of INDOX Cancer Research Network. His main interest is in colorectal (bowel) cancer and other chronic, non-communicable diseases. Incidence of colorectal cancer in India has been relatively low historically; understanding why may help us establish risk factors and also lead to new treatments.

Dr Jay Berkley tells us about his work on childhood nutrition and immunity in East Africa. Dr Jay Berkley works in the KEMRI/Wellcome Trust Collaborative Research Programme in Kilifi, Kenya. His research interests include tackling infection and inflammation to prevent mortality in malnourished children. He is also an expert advisor on severe acute malnutrition to the Ministries of Health, and the World Health Organisation.

Dr Holm Uhlig talks about the role of the immune system in our gastrointestinal tract. 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 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. Professor Richard Cornall aims to understand the causes of autoimmune diseases. Autoimmunity occurs when the immune system which is normally designed to attack pathogens ends up attacking the body. Professor Cornall is also interested in 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 George Warimwe talks about his research on Rift Valley Fever. Dr George Warimwe is working with the International Livestock Research Institute (ILRI) A Centre of Excellence in Africa, and the Jenner Institute to develop a vaccine against Rift Valley Fever in humans, that will also be useful as a vaccination against the disease in livestock.

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. Dr Katherine Owen investigates the different characteristics of monogenic diabetes with the aim of creating systematic diagnostics for aetiology of diabetes, and implementing that in clinical care. The ultimate aim is to promote personalized medicine for everybody with diabetes.