Anaesthesia and Intensive Care
The principal research interests of the Division of Anaesthesia and Intensive Care relate to vascular reactivity, computer simulation of physiological function, the septic patient, and muscle function in critically ill patients.
Studies of vascular reactivity have included investigation of the effects of anaesthetic agents on cerebral blood flow and laboratory investigations into the effects of substances present in the serum of septic patients on contractility of isolated coronary arteries. A programme of investigation into the potential for a safe and effective cerebral vasodilator to treat patients with cerebrovascular spasm will start shortly.
Very complex computer simulations have been developed to study the lung and the cerebral circulation. These simulations can be used to study extreme conditions which could not be investigated in man. They are also able to avoid the need for animal experimentation.
Recent studies have centred on changes in muscle in critically ill patients, including genetic predisposition to myopathy in critical illness.
Much of the research in the Division is conducted in collaboration with other Schools within the university.
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Brain Tumour Research - The Children’s Brain Tumour Research Centre (CBTRC)
Brain tumours are the leading cause of childhood cancer deaths in the UK. It is increasingly clear that improving in our ability to cure children with brain tumours and reduce the considerable morbidity they suffer will only come through a better understanding of the underlying biology of these varied and presently difficult to treat tumours.
The development of the Children’s Brain Tumour Research Centre set out to meet this challenge and now links over 60 researchers from eight departments across the University and Nottingham University Hospital Departments conducting clinical and scientific research directed at increasing our beginning to use this knowledge to optimize the health outcomes for the child and family. In a forward-looking multidisciplinary research programme linking basic science to patient-centred care we are currently testing hypotheses concerned with neurodevelopment, tumour biology, health services research linked to processes of referral at diagnosis, application of novel imaging and genetic techniques aimed at comprehensive assessment of tumour biology, optimisation of drug selection and CNS targeting, clinical trials of novel therapies, classification of specific brain injury syndromes and techniques for their limitation as well as the development and application of methods for measuring health outcomes during and after treatment as experienced by children and young people.
In May 2005, the University appointed Professor Grundy as Professor of Paediatric Neuro-Oncology, the first such chair in Europe, bringing a substantial cancer genetic translational research programme linking basic science to patient care
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Cardiovascular Medicine
The Division of Cardiovascular Medicine occupies accommodation within the Queens Medical Centre in Nottingham where there is good access to excellent research laboratories and also to the clinical facilities within University Hospital. The Division comprises academic staff (both clinical and non-clinical), postdoctoral scientists, technicians and administrators who work together to conduct research and provide teaching to medical students, students registered for a Postgraduate Higher Degree and young doctors in training. Most research is carried out on the diagnosis and treatment of cardiovascular disease, and includes studies on basic mechanisms of disease as well as the therapeutic options that are available.
The Division hosts the Thrombosis and Haemostasis Research Group, led by Dr Sue Fox and Professor Stan Heptinstall, Professor of Thrombosis and Haemostasis where the main focus of attention is the contribution of platelets and other blood cells to these pathological and physiological processes. Current research is focused on the roles of adenosine diphosphate and prostaglandin E2 in platelet function, the involvement of P2Y receptors and EP receptors in mediating the effects of these agents, and on approaches to modifying their effects using selective receptor blockade. There is a major emphasis on identifying simple methods that can be used to measure platelet function in patients with cardiovascular disease and to monitor the effectiveness of treatment. The Group works closely with the pharmaceutical industry in this regard. The Group operates in well-equipped laboratories with access to specialist equipment that includes state-of-the-art flow cytometers (BD LSR II, BD FACSCanto II and BD FACScan), HPLC equipment, Haematology Analysers (Sysmex and Ultra-Flo) and various aggregometers (Biola, Biodata PAP-4, Helena AggRAM and Multiplate. This extensive range of equipment is used to undertake studies of the blood cells involved in both thrombosis and haemostasis.
Through Dr David Gray, Associate Professor and Reader, the Division has a reputation for high quality epidemiology and health sciences research in the fields of myocardial infarction and health economics. There is a close working relationship with cardiology NHS colleagues within both the University Hospital and Nottingham City Hospital in terms of medical teaching and research. Within that larger cardiology group are five interventional, two electrophysiological and two imaging/heart failure consultants. The Division also has an international history of clinical trials particularly in acute or chronic atherothrombotic diseases. Most of the trials have involved assessment of novel or "improved" antithrombotic drugs, and these are trials in which Professor Robert (Bob) Wilcox has played a prominent part. Following his recent retirement Bob is now an Emeritus Professor so is still around to offer advice.
A new professor with research interests that complement and strengthen existing research programmes within cardiovascular medicine is currently being sought.
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Dermatology
The Centre of Evidence-Based Dermatology (CEBD) is focussed on health technology assessment and epidemiology as applied to people with skin problems. The Centre at King’s Meadow Campus currently hosts 27 research staff, and is led by Professor Hywel Williams and Associate Professor Dr Kim Thomas. The Centre houses the
Cochrane Skin Group
, which identifies research priorities through systematic reviews, which are then picked up and addressed by the
UK Dermatology Clinical Trials Network
– a national network of mainly dermatologists who conduct independent randomized controlled trials.
The Centre also works closely with NHS Evidence, NHS Choices and NHS Directin order to ensure that high-quality information is disseminated to the relevant community of users.
Clinical research fellows also conduct important methodological work especially into the field of childhood eczema. The Centre is also recipient of a National Institute for Health Research (NIHR) Applied Programme Grant on identifying and reducing uncertainties in the treatment of people with skin diseases. Themes of the Programme Grant include prevention of eczema, treatment of eczema, vitiligo, squamous cell carcinoma and a national clinical trial of treatments for pyoderma gangrenosum. Over the next five years, the CEBD will continue to increase its portfolio of independent clinical trials by expanding into Europe and then globally.
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Early life nutrition and disease
We have an established internationally-recognised research programme investigating the impact of diet in early life on later health and disease based in the Division of Child Health. We undertake Endocrine, metabolic and molecular studies in order to measure the impact of maternal diet on the physiology of pregnancy plus fetal and postnatal growth in both humans and a range of animal models. These have identified candidate mediators and mechanisms for early life programming and how they may influence later energy balance. We are thus able to examine nutritional interventions designed to prevent adverse adipose tissue development and later hypertension. We are also conducting novel studies examining the impact of environmental challenges during pregnancy, lactation or juvenile life in order to establish the short- and long-term health outcomes, together with the extent to which risk of later obesity can be programmed in early life.
We have been lead members of a European Union Sixth Framework Programme Integrated Project on programming effects of early nutrition on long-term health entitled Early Nutrition Programming - long term follow up of efficacy and safety trials and integrated epidemiological, genetic, animal, consumer and economic research (EARNEST). Additional funding is held from the British Heart Foundation and Medical Research Council (MRC) and University of Nottingham Special Trustees.
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Gastrointestinal Surgery
The Division of Gastrointestinal Surgery is part of the
Nottingham Digestive Centre and participates in collaborative research projects in medical and surgical gastroenterology. The division enjoys an international reputation for its pioneering work in colorectal cancer screening, but this is just one of a number of areas of research.
Current areas of research include:
1) Screening for colorectal cancer, early detection of adenomas and cancers and the use of new prognostic markers.
2)Enhanced recovery after gastrointestinal surgery, optimising intravenous fluid delivery for surgical patients.
3) Pharmacological treatments for anal fissures.
4)Pharmacological treatments for haemorrhoids
5)Therapeutic interventions in the treatment of faecal incontinence.
6)Pathogenesis of diverticular disease and gastro abdominal pain.
7)Tissue engineering for liver regeneration.
8)Sepsis in the surgical patient
The Division of Gastrointestinal Surgery has excellent laboratory facilities for measuring gastrointestinal function including ambulatory systems for the upper and lower GI tract.
The department also carries out extensive organ bath work using in vitro preparations for pharmacological studies of sphincter and bowel. We have facilities for molecular biology and functional gastrointestinal imaging.
A list of publications and further details on the work can be obtained through the Nottingham Digestive Diseases website and the University of Nottingham website.
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Maternal and Fetal Health
Nottingham’s Schools of Molecular Medical Sciences and Clinical Sciences (Division of Human Development) are the leads in the multi-centre Genetics of Pre-Eclampsia (GOPEC) study. Although the first phase is complete, trans-national genetic collaborations are developing from the study, and we plan to follow up the babies as they reach school age. We are also currently undertaking other long-term collaborative (Universities of Leicester, Newcastle 0n Tyne and Bern, Switzerland) follow-up studies of mothers and babies who have been exposed to pre-eclampsia. We collaborate with the Schools of Molecular Medical Sciences and Biosciences in studies of seleniaum-containing antioxidant proteins in healthy and hypertensive pregnancy. The genetics biochemistry and function of the renin-angiotensin system in normal and pathological (pre-eclamptic) pregnancy is another major interest of our group in collaboration with the Cambridge Institute for Medical Research. These studies are complemented by studies of myometrial physiology and pathology. A further collaboration is with the School of Electrical and Electronic Engineering, relating to the validation and use of a new, very small and portable, fetal heart rate monitor and the derivation of physiologically-relevant information from the fetal electrocardiogram.
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Medical Gastroenterology
Medical Gastroenterology is integral to the WDDC and was graded 5* (the top grade) in the last research assessment exercise.
We employ a broad range of research methodologies. We have experts in basic and translational research who use cutting-edge molecular biological, cell biological and microbiological techniques. We perform ex vivo research on human tissue using a range of modern technologies. We have facilities for detailed patient-based physiological, therapeutic and imaging research. We perform local clinical trials and co-ordinate national and international multi-centre studies. Finally we have a leading GI epidemiology unit which adds a unique angle to our research approach.
Research interests incorporate virtually all of GI clinical research. We have a leading therapeutics programme, focussing recently on development of safe non-steroidal anti-inflammatory drugs and on the chemotherapeutic potential of these and related compounds. We have a large basic and clinical research programme in inflammatory bowel disease. Neurogastroenterology is a major interest, particularly the genesis of symptoms in irritable bowel syndrome and the development of new diagnostics and treatments. In collaboration with the Sir Peter Mansfield MRI Centre, we research novel imaging of the bowel and visceral pain and taste pathways in the brain. We also develop new endoscopy imaging techniques and new therapeutic strategies. Several of our investigators lead programmes in GI infections, including the ulcer and stomach cancer-causing bacterium Helicobacter pylori and the hospital acquired pathogen Clostridium difficile. We are particularly interested in chemotherapeutic approaches to prevent GI cancers and in developing rational screening and surveillance programmes. Recently we have started a large programme of GI stem cell research. Finally, we have a major interest in hepatology, in particular in hepatitis C infection, the “new” disease of non-alcoholic fatty liver and the effects of drugs on the liver.
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Medical Physics (Division of Radiological and Imaging Sciences)
The Medical Physics Group is developing methods of studying physiological processes and drug delivery in man. These include radiolabelled conjugates and molecular imaging probes to target therapies in a range of conditions including bladder cancer. In particular, we are developing new methods for assessing gastrointestinal transit; for example, in the investigation of chronic constipation in children and tablet swallowing in the elderly.
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Neurology - Clinical Neurology
The Division of Clinical Neurology's main interest is multiple sclerosis (MS). We investigated paradoxically shared signalling pathways for interferon type 1 (IFN), an MS treatment, and interleukin-12 (IL-12), a proinflammatory cytokine detrimental in MS. We showed that different factors modulate the pathway differently when activated by IFN and IL-12, and that MS patients have an intrinsic IFN signalling deficit. We showed that astrocytes can express and produce most elements of the IL-12 family of cytokines.
We have shown induction of regulatory T (Treg) cells that protect against autoimmunity, by steroids, and induction of the main transcription factor for Treg cells, foxp3, by steroids and IFN. We investigate how IL-12 suppresses signalling pathways essential for Treg function.
We also investigate the role of T cells producing IL-17 (Th17) cells in MS. We have identified a Th17 marker.
Another line of investigation relates to the role of the innate immune system (comprising dendritic cells and other antigen presenting cells) in regulating inflammatory demyelination in the central nervous system (CNS). Specifically we are focusing on the role of Toll-like receptors (TLRs) in modulating the function of Tregs and other classes of immune cells in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Studies in EAE will be essential for preclinical testing of new treatments for MS and to address mechanisms of CNS inflammation, demyelination, and neuronal damage in vivo.
On the imaging side, we have applied advanced MRI (diffusion tensor imaging, magnetisation transfer imaging, T1 mapping) to quantifying MS pathology. We developed an accurate method of measuring spinal cord area.
In the next 1-2 years we will continue studies to determine whether immunotherapy normalises the MS IFN signalling deficit. Detailed studies of Th17 cells and the novel marker we identified are planned. Treg and Th17 regulation by cytokines, vaccines, and parasites will be studied. We plan an immunomodulation trial of hookworms in MS. We will validate several novel MS targets in experimental models. We will embark soon in a high field (3T and 7T) MRI study of MS, where some of the subjects will be investigated serially.
Facilities: cell and molecular biology, tissue culture, PCR, image analysis software, access to flow cytometry and real time PCR.
Contacts: Professor Cris Constantinescu (cris.constantinescu@nottingham.ac.uk), Head of Division, and Dr. Bruno Gran (bruno.gran@nottingham.ac.uk), Clinical Associate Professor.
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Nottingham Digestive Diseases Centre (NDDC)
The WDDC has 38 Principal Investigators, fifteen of whom are full Professors, making it the biggest clinically-based gastrointestinal research grouping in the UK. Its core members are within three divisions of the School of Medical and Surgical Sciences:
Medical Gastroenterology,
Pre-Clinical Oncology, and
Gastrointestinal (GI) Surgery. However, it also includes research active NHS consultants and researchers in the GI and liver fields from other schools within the University. It offers research training leading to PhD and DM degrees. For details of the three divisions that make up WDDC please click on the appropriate link.
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Ophthalmology and Visual Sciences
Research interests include:
Antimicrobial peptides; corneal epithelial wound healing; ocular surface reconstruction, corneal stem cell research, and age-Related Macular Degeneration (AMD).
Details of novel expertise
Dr Hopkinson has extensive expertise in proteomic analysis techniques. Mr Imran Mohammed has expertise in real time PCR.
Over the last decade the Cornea and Anterior-Segment unit of the Department of Ophthalmology has established itself as an internationally recognised centre of excellence in the management of complex ocular surface disorders. Nationally it is without doubt one of the leading centres in this area attracting referrals of patients from consultant ophthalmologist colleagues from across the country, from Europe and telemedical consultations from the USA, Middle East, Indian Subcontinent, Malaysia and other countries.
The division has a track record of close collaboration in clinical and basic research at all levels i.e. within the University with other schools, nationally with other centres with expertise in ocular surface reconstruction and internationally with centres in Europe and the USA. These have resulted in various visits between centres of individuals and also in joint publications in international journals. This international recognition for combined clinical and basic-research has led to considerable interest from international students, clinicians and researchers wishing to undertake research studies within the department.
The centre has also liased regularly with the Medical Directors of the UK eye banks in maximising eye donation (and hence material for ocular surface reconstruction) and storage and processing of amniotic membrane. Our applied laboratory research has directed clinical practice in the eye banks and our recent work, published in January 2006 in the British Journal of Ophthalmology, has informed a change in practice in the eye banks such that by retaining a rim of conjunctival tissue at the time of eye retrieval we can maximise retention of limbal stem cells and incease the growth potential of transplanted donor material for epithelial cell regeneration.
Under the new DOH code of practice for Tissue Laboratories, Nottingham is amongst a few centres that have a dedicated purpose built facility. We will be in a position to provide standard AM-derived bioengineered tissue constructs for use by surgeons through the country enabling the benefits accruing from this work to be disseminated through the NHS to the advantage of all patients requiring such surgery. Furthermore, considering the clinical potential of the construct and the novelty of the concept, it is envisaged that enough information will be generated for the successful application of a worldwide patent. In this regard, a patent application for a significant improvement in the processing technique of the AM has already been filed.
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Orthopaedic and Accident Surgery
The Division has wide ranging research interests all of which address clinical problems. Our main areas of research are in arthritis pain, implant-related infection, shoulder implant design and injury prevention. We have active collaborations with clinical colleagues within the NHS specifically in trauma and orthopedics, rheumatology, radiology, ENT and diabetology; and scientists in Pharmacy, Neurosciences, Engineering, ENT and Rheumatology. Professor Scammell (Head of Division) is part of the Arthritis Research UK Nottingham Pain Centre and Dr Fuller (Director of the MSc in Sport and Exercise Medicine) leads the ‘Football for Health’ promotion programme for children.
Current areas of research interest include:
1) Inflammation and bone repair
2) Arthritis pain and new therapeutic targets for pain
3) A prospective randomized trial of surgical treatment for distal radial fractures
4) Antimicrobial biomaterials: bone graft substitutes, middle ear infections and urinary catheters
5) Skin disinfectants
6) Risk assessment and injury prevention in sport
7) Football for Health promotion programme
8) Implant design and shoulder surgery
For more details and a list of recent publications, please see the website.
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Otorhinolaryngology and Head and Neck Surgery
The division comprises clinical and academic expertise in ENT and in Audiology and Speech and Language therapy. It hosts the NIHR funded National Biomedical Research Unit in Hearing established in 2008 and funded from the National Institute of Health Research (NIHR) as one of 16 Biomedical Research Units (BRUs) to improve the pathway of translating basic research findings into clinical benefit. The BRU in Deafness and Hearing Problems has since established itself as a flagship research unit addressing major clinical issues in the ENT and audiological management of hearing loss and tinnitus. Key partners are the University of Nottingham, Nottingham University Hospitals Trust and the MRC Institute of Hearing Research. Nottingham has a long established critical mass of staff working in fundamental hearing research, translational hearing research, ENT and Audiology, with the UK’s largest programme in cochlear implantation. There are strong collaborative links across this partnership. The BRU also has excellent relations with industry and with other NIHR organisations and in the past year has attracted over £1m in external funding.
In August 2011, NIHR awarded the BRU in Deafness and Hearing Problems a further £6.25m to develop and expand the research portfolio through to March 2017. Research areas take advantage of exciting new scientific opportunities and closer alignment to the research strengths of the partnership enhances collaborative possibilities. There are five primary research areas:
- Tinnitus etiology and management, led by Prof Deb Hall
- Habilitation for hearing loss, led by Mrs Melanie Ferguson and Prof Dave Moore
- Sensorineural plasticity and rehabilitation, led by Prof Deb Hall and Prof Alan Palmer
- Cochlear implantation, led by Dr Doug Hartley and Prof Gerry O’Donoghue
- Paediatric ENT/Audiology, led by Prof John Birchall and Dr Heather Fortnum
These areas are underpinned by methodology-based research in:
- Large-scale studies of hearing and hearing health, led by Dr Heather Fortnum and Prof Dave Moore
- Advanced imaging, led by Prof Richard Bowtell and Prof Deb Hall
Research in ENT is mainly concerned with:
- Mucin production by the middle ear and its relation to biofilms present in the middle ear effusion.
- Clinical research within the Nottingham Cochlear Implant Service
- Laboratory based projects on the relationship of perennial rhinitis and allergy
Studentships
For more information contact:
e: heather.fortnum@nottingham.ac.uk
w: www.hearing.nihr.ac.uk
Resear
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Pre-Clinical Oncology
Research in the Division is translational and involves strong collaborations with clinicians and industry. Current research areas include:
- Use of reporter constructs for the imaging of key biological parameters within tumours, such as growth, apoptosis, angiogenesis and metastatic pathways and stem cell evolution; modeling the tumour microenvironment including the process of epithelial-mesenchymal transition
- Analysis of paracrine interactions in tumour progression including HGF/c-met, H-edgehog, Gastrin and Fibroblast growth factors
- Delivery of siRNAs using non-viral and viral delivery systems for target validation
- Pre clinical validation/target identification of traditional Chinese medicines
- Contribution of ß-catenin controlled intestinal stem-cell associated homeodomain transcription factors to carcinogenesis and the involvement of the tumour suppressor gene, FBW7 a ubiquitin ligase, in intestinal malignant progression.
This research portfolio is undertaken by a team of 15 lecturers, research nurses, research fellows and post-doctoral research scientists with funding from Cancer Research UK, the Medical Research Council, Innovation-China UK, National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), and industry.
We currently have 15 PhD students and 2 DM at different stages in their studies. Postgraduate students within the Division carry out their research within the active team of scientists described above who provide training and laboratory supervision. In addition to regular meetings with their academic supervisors, they participate in laboratory meetings and journal clubs.
The Division was awarded a 5 year research grant from Janssen Pharmaceutica NV to establish an Ex Vivo Cancer Pharmacology Centre of Excellence. This grant will allow the University division to continue its world leading work in the development of sophisticated cancer models to examine potential new drugs for anti-cancer activity.
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Radiological and Imaging Sciences
Our research aims are to develop and validate neuroimaging markers of CNS diseases (stroke and carotid artery disease, multiple sclerosis, Parkinson’s disease, Alzheimer disease, mental diseases). We are particularly interested to develop markers for early preclinical diagnosis and to quantify treatment effects. We focus on advanced magnetic resonance imaging and spectroscopy techniques and perform multidisciplinary clinical, translational and methodological research projects (quantitative MRI and morphometry, diffusion tensor imaging, proton spectroscopy, functional and pharmacodynamic assessment, combined EEG-fMRI brain conncectivity studies).
We have an active interdisciplinary research training programme interfacing clinical and nonclinical fellows and postgraduate students. Main collaborations are with clinicians and academics in Clinical neurosciences, Vascular surgery, Stroke medicine, Anaesthesia, and researchers from the Sir Peter Mansfield Centre, the School of Biomedical Sciences, School of Computer Science and Department of Mathematics.
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Reproductive Medicine
We have a large infertility research group based at Queen's Medical Centre (QMC) and work with the large animal facility at the University's Sutton Bonington campus. Studies of ovarian development using mono-ovulatory species have led to physiological culture systems, gonadotrophin suppression models and cortical autografts (developed to restore fertility) to advance understanding of folliculogenesis at cellular and molecular levels (supported by Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council (BBSRC) and industry).
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Respiratory Medicine
The Division of Respiratory Medicine is based within the Centre for Respiratory Research and has close links with researchers who have an interest in respiratory diseases within epidemiology and child health in the Centre. A unique feature of research within our Centre is its broad base in the cell biology, clinical research and epidemiology of respiratory diseases. This allows a “molecules to man” translational approach to respiratory science and its application to human disease. This environment has been strengthened by the recent award of a Respiratory Biomedical Research Unit (BRU), one of only three in the country which has enhanced our ability to deliver important clinical trials and translational research in asthma, cystic fibrosis and other lung diseases.
The cell and molecular biology group (Knox, Pang, Jenkins) are interested in the role of lung structural cells in inflammatory (asthma, cystic fibrosis, pulmonary hypertension) and fibrotic lung diseases (idiopathic pulmonary fibrosis). Our studies have shown that structural cells have important synthetic functions which contribute to the pathogenesis of several lung diseases. We have been particularly interested in the transcriptional regulation of inflammatory gene expression in airway cells particularly delineating the role of transcription factors and chromatin remodeling (histone H4 acetylation) and have been leaders worldwide in developing methods for studying this in primary human lung cells, particularly smooth muscle and fibroblasts (Journal Biological Chemistry 2003 278:29366-75, Journal Biological Chemistry 2003 278:18868-76), eotaxin (FASEB J 2001 15:261-269, Journal Immunology 2008 181 3503-14), VEGF (FASEB Journal 2001 15:2480-8, Journal Biological Chemistry 2008 283 35337-53) and COX-2 (Journal Immunology 2003 170:1043-51, Journal Biological Chemistry 2003 278:49954-64, Molecular Cellular Biology 2009 29 4325-39). Jenkins is particularly interested in TGFbeta signalling (American Journal Pathology 2009 174 1264-79, Journal Clinical Investigation 2006 116 1606-14).
The translational research group (Harrison, Shaw, Bolton, Knox, Jenkins) is interested in early and late phase clinical trials in asthma, Chronic Obstructive Pulmonary Disease (COPD), Idiopathic pulmonary fibrosis (IPF) and cystic fibrosis and developing new biomarkers to monitor disease activity (Lancet 2005 365 573-8, Lancet 2004 363 271-5).
The groups within the Division have funding from the Medical Research Council, Wellcome, NIHR, charities and industry of more than £4m in addition to the National Institute for Health Research (NIHR) funded BRU (£6m) and EU funding (part of a 23m Euro Ubiopred consortium).
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Rheumatology
The main research interests are in osteoarthritis (OA), pain and crystal-associated arthritis. Principal types of study undertaken are: community-based epidemiological and genetic studies for associations, risk factors and outcomes for OA; gene-environmental interaction studies on knee and hip OA; community based clinical trials in OA and gout; laboratory investigation of angiogenesis and neurovascular factors involved in arthritis; and meta-analyses and evidence-based recommendations on diagnosis and management of OA and crystal arthritis.
We have dedicated office space and shared-user laboratory facilities in the Clinical Sciences Building on the City Hospital campus; several large well-characterised cohorts of community participants with large joint OA and non-OA controls; and expanding repositories of sera, DNA and human joint tissues.
Current work includes: genome wide-scans and gene-environmental interaction studies in cohorts with OA; identification of possible new morphological risk factors for large joint OA; a large randomised clinical trial (RCT) examining the effectiveness of a nurse-led intervention for community-based patients with gout, and the effect size of placebo and contextual response in RCTs of fibromyalgia and rheumatoid arthritis.
In 2009 Nottingham was awarded the status of the Arthritis Research Campaign UK Centre of Excellence for Pain in Arthritis. The Centre opened in June 2010 and a linked series of basic and applied research that focuses on osteoarthritis pain is now underway in collaboration with other departments within the University.
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Sports and Exercise Medicine
The Centre adopts a multidisciplinary approach to research and undertakes clinical and non-clinical research into issues related to injury prevention, treatment and rehabilitation. Researchers collaborate closely with a broad range of national and international sports governing bodies in order to inform and support the Centre’s research programme.
The highly successful MSc in Sports and Exercise Medicine is administered from within the Division of Orthopaedic & Accident Surgery and is headed by Dr Kim Edwards, who is a world leader in the field of risk assessment and injury prevention in sport.
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Stroke Medicine
The main interests of the Division are in the treatment of acute stroke, enhancing recovery and stroke prevention. Acute interventions are tested in the Stroke Trials Unit including investigation of blood-pressure control (MRC ENOS trial of glyceryl trinitrate, BHF telmisartan trial), and mobilisation of endogenous stem cells (MRC STEMS II tri al of granulocyte colony stimulating factor. Other studies focus on the effect of PC-based visual field training in stroke rehabilitation. The NIH ARUBA study is assessing stroke prevention in patients with unruptured brain arteriovenous malformations. The Division of Stroke Medicine hosts the mid Trent part of the UK Stroke Research Network.
The translational research in the Division focuses on the relative contributions of protein kinase C b, vascular growth factors e.g. VEGF, small GTP-binding proteins such as Rho and Rac as well as oxidative stress associated with excessive generation and/or reduced metabolism of reactive oxygen species to ischaemic stroke-related blood-brain barrier leakage and diabetic cerebrovascular damage.
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Therapeutics & Molecular Medicine
Research in the Division of Therapeutics and Molecular Medicine is centred on understanding the molecular pathology and genetics of lung diseases; in particular asthma, COPD, lymphangioleiomyomatosis (LAM) and pulmonary fibrosis. As two of the group leaders are active clinicians, our laboratory program is complemented by translational studies and clinical trials. We have recently also made a major investment in functional lung imaging including a state of the art clinical hyperpolarised gas MRI research facility. The Division is based in state of the art laboratories within the Queens Medical Centre and is part of the Nottingham NIHR Biomedical Research Unit in Respiratory medicine.
Senior research active academics include Dr Simon Johnson (Reader and Head of Division), Prof Ian P Hall (Dean of Medicine), Dr Ian Sayers (Associate Professor) and Prof Thomas Meersmann (Professor of Translational Imaging). Our current projects include the role of matrix metalloproteases in tissue remodelling in COPD, asthma and LAM. Epithelial/mesenchymal cell interactions in the lungs and clinical trials in LAM (Johnson). Hyperpolarised gas lung imaging (Hall / Meersmann). Molecular genetics of asthma and COPD using large cohorts (Hall / Sayers). Calcium signalling and contraction in the airway and the role of structural cells in remodelling (Hall). The role of bronchial epithelial cell dysfunction in airway diseases (Sayers). Our work has resulted in recent publications in The New England Journal of Medicine, Nature Genetics, The Journal of Immunology, Allergy, The American Journal of Physiology, Thorax and others. Funding for the Division currently comes from research councils and charities including the Medical Research Council, Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council, Asthma UK, The British Lung Foundation and LAM Action.
The Division comprises around 30 staff including group leaders, postdoctoral scientists, technical and administrative staff and around 10 clinical and non-clinical PhD students. We have supervised a large number of higher degrees, and on average three new PhD students start their post-graduate studies with us each year.
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Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM)
The Stem Cell Biology Group comprises four academics who are part of the inter-school Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM).
Professor Lorraine Young’s (Director of STEM) laboratory studies the epigenetic changes that are induced during nuclear reprogramming. The Group investigates the epigenetic alterations induced by maternal nutrition and IVF-associated technologies and their health/disease inducing implications for later fetal development and adult life. A variety of model systems are used, including human embryonic stem cells and induced pluripotency stem cells that can be differentiated into disease-relevant tissues of the fetus. Another major strand of the work focusses on adapting laboratory protocols for culturing human pluripotent stem cells to the automated platforms that industry will require for multi-well drug screening and to produce sufficient cells that patients will require for multiple regenerative medicine applications.
Prof Chris Denning's (Course Director of the MSc in Stem Cell Technology; Professor in Stem Cell Biology) group is interested in four key areas:
- Standardising, improving and automating culture of human pluripotent stem cells (hPSCs)
- Using genetic modification to genetically tag or change the function of hPSCs to gain a greater understanding of biology
- Generating induced pluripotent stem cells by genetically modifying somatic cells (e.g. skin cells) to create new possibilities for investigating genetic diseases such as Duchenne muscular dystrophy or Long QT syndrome, both of which affect the function of the heart
- Differentiating hPSCs into cardiomyocytes to improve understanding of biology, disease and drug safety.
Dr Alexey Ruzov (Lecturer) studies the role of DNA methylation and 5-hydroxymethylcytosine regulatory mechanisms involved in the pluripotency and differentiation of embryonic stem cells, the differentiation of neural stem cells and in cancer stem cells. The work aims to evaluate the functional consequences of these epigenetic modifications, their evolutionary significance and to uncover how their manipulation can be applied to current stem cell technologies.
Dr Virginie Sottile's (Lecturer) group is interested in the differentiation potential of adult stem cells, from both bone marrow and brain origin. The lab investigates the differentiation of mesenchymal and neural stem cells in comparison to pluripotent stem cells. The Group uses stem cell isolation, in vitro culture, gene expression analysis and transplantation models to investigate the mechanisms governing cell fate decisions in stem cells, evaluate their potential use for tissue repair, and understand their role in disease and neoplasia.
The Group runs the MSc in Stem Cell Technology, which in 2007, was the UK's first MSc course in this exciting and emerging field.
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