Barts and The London School of Medicine and Dentistry_Our Research_Our Mission

OUR RESEARCH OUR MISSION

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Introduction

“At Barts and The London School of Medicine andDentistry our outstanding research underpins ourcommitment to excellent education and clinicaldelivery, and has been transformed over the last fiveyears under the leadership of our Warden Professor Sir Nicholas Wright. This has been confirmed by theoutstanding results for Barts and The London in the2008 Research Assessment Exercise.

“Since 2003 there has been a 45 per cent increase in research grants and contracts. Research councilgrants have doubled, and £94.3 million in new grantsawarded since 2005. In terms of 2006-7 researchspend, the School ranked 11th among UK medicalschools, exceeding that of many major metropolitanmedical schools including Newcastle, Nottingham,Cardiff, Leeds, Sheffield and Southampton. We werejoint first in the UK for success in the MRC ClinicalResearch Training Fellowship competition.

“Barts and The London is the largest recipient ofcharitable income among UK medical schools. Thisincrease has been in part due to the recruitment ofworld-class researchers, strategically appointed to addvalue to existing areas of excellence. Thus the Schoolboasts world-leading groups in Cancer, Inflammation,Cardiovascular, Endocrinology, Epidemiology,Gastroenterology and Neuroscience research.

“Academics in the medical school have been at the forefront of gaining National Institute for HealthResearch (NIHR) funding, and have just won a £6 million award for a Cardiac Imaging BiomedicalResearch Unit. With high quality staff, Barts and TheLondon seeks to increase its funding from NIHR, MRC,Wellcome Trust, CRUK and the other major charities byat least 5 per cent per year.”

Professor Tom MacDonaldDean for ResearchBarts and The London School of Medicine and Dentistry


Contents:

Bringing the Benefits of International Excellence to our Communities 1

Queen Mary, University of London 3

Our Education Mission 6

Our Clinical Engagement 7

Our Research Excellence 9

Cancer 14

Stem Cells 20

Genetic Basis of Common and Rare Diseases 23

• Hypertension and Heart Disease• Skin diseases• Diabetes and periodic fevers• Obesity• Coeliac disease• Down’s Syndrome• Bone Marrow Failure

Infection, Inflammation and Repair 30

Basic and Translational Neuroscience 35

Dentistry 39

Preventive Medicine and Public Health 44

For further information visit:

smd.qmul.ac.uk

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Bringing the benefits of internationalexcellence to our communities

The 2008 Research Assessment Exercise results showedBarts and The London School of Medicine and Dentistryjoining Oxford, Cambridge, Imperial College and UniversityCollege London in the top 5 research-active medical anddental schools in England.

According to rankings published in the Times Higher Education, Barts and The London scored consistently in the top five:

• Dentistry was ranked 1st equal with Manchester based on 3* and 4* outputs,and 2nd overall out of 14 UK dental schools.

• In Cancer, we were ranked 3rd out of 14 submissions in terms of 3* and 4*outputs and joint 5th in the UK overall, ahead of Oxford, Imperial, KingsCollege London and University College London

• The Institute of Cell and Molecular Science, returned in Hospital Subjects, wasranked joint 1st with Cambridge and Edinburgh in terms of 3* and 4* outputsand was joint 7th overall out of 28, ahead of Manchester, Newcastle andSouthampton.

• The Wolfson Institute of Preventive Medicine, returned in Epidemiology andPublic Health, was 2nd out of 21 in terms of 3* and 4* outputs, and 3rdoverall, ahead of Oxford, University College London and Bristol

• In Health Services Research, we were ranked 4th overall out of 28, ahead of Oxford, University College London and Kings College London

• The William Harvey Research Institute, returned in Preclinical and HumanBiological Sciences, was ranked 3rd in terms of 3* and 4* outputs, and 4thoverall out of 13, ahead of Kings College London, Bristol and Nottingham.

Barts and The London School of Medicine and Dentistry offers internationallevels of excellence in research and teaching. We serve a population of unrivalleddiversity in east London and the wider Thames Gateway, with a high prevalenceof diabetes, hypertension, heart disease, tuberculosis and other chronic lungdiseases, HIV, oral disease, and cancer.

To follow the London Underground from Westminster to Canning Town, in healthterms, is to see a reduction in life expectancy of one year for each station – anastonishing and scandalous six years in all. Barts and The London is committed to changing this situation.

The School has almost 1,000 members of staff, consisting of over 650academics and around 350 support staff. The School’s total annual turnover isapproximately £86 million of which over £40 million is competitively awardedexternal research income additional to that received from HEFCE, placing Bartsand The London in the top tier of research active medical and dental schools.

Through partnership with our linked trusts, notably Barts and The London NHSTrust, and our associated University Hospital Trusts – Homerton, Newham,Whipps Cross and Queen’s (Romford) – the School’s research and teaching isinformed by an exceptionally wide ranging and stimulating clinical environment.

Barts and The London School of Medicine and Dentistry

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At the heart of the School’s mission lies world class research, the result of a focusedprogramme of recruitment of leading researchgroups from the UK and abroad, and a £100million investment in state-of-the-art facilities.Research is focused on:

• translation of basic research into man

• cancer

• cardiovascular

• dentistry

• inflammation

• endocrinology/metabolism

• immunology and infectious diseases

• skin disease

• genomics

• neuroscience

• gastroenterology

• epidemiology

• public health and primary care

The School is nationally and internationallyrecognised for research in these areas. Itsfundamental mission, with its partner NHSTrusts, and other linked organisations, such asCR-UK, is to ensure that that the best possibleclinical service is underpinned by the very latestdevelopments in scientific and clinical teaching,training and research.

We pride ourselves on being a School that iscommitted to:

• achievement of international excellence in our chosen areas of research and education

• and through this, in collaboration with ourNHS partners, contributing to our uniquelycomplex and diverse social and clinicalenvironment in east London and the ThamesGateway, which offers research, teaching andclinical opportunities unrivalled in the UK



Queen Mary, University of London


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Barts and The London School of Medicine and Dentistrydraws strength from being part of Queen Mary, University of London, one of London and the UK’s leading research-focused higher education institutions.

One of the largest of the colleges of the University of London, Queen Mary's3,000 staff deliver world class degree programmes and research across a widerange of subjects in Humanities, Social Sciences and Laws, Medicine andDentistry and in Science and Engineering.

Queen Mary, as a member of the 1994 Group of research-focused universities,has made a strategic commitment to the highest quality of research, but also tothe best possible educational, cultural and social experience for its students.Indeed, we believe that a vibrant research environment means that our studentshave access to the world's leading experts in their chosen subjects.

Like Barts and The London, Queen Mary's distinctiveness arises from itscommitment to an engagement with international excellence in education andresearch and a twin commitment to bring that engagement to bear on its Londonand Thames Gateway environment through educational outreach and knowledgetransfer projects.

Queen Mary has been ranked in the top 14 universities in the UK and in the top100 in the world and has consistently been in the top group of universities foryear-on-year increases in funding from the Higher Education Funding Council.

The results of the 2008 Research Assessment Exercise confirmed Queen Mary’splace in the very top group of research-led universities.

According to tables published in the Times Higher Education, Queen Mary hasbeen ranked 13th in the country out of the 132 institutions which submitted for the exercise.

The Guardian placed Queen Mary even higher, 11th in the UK.

Queen Mary was ranked ahead of severalRussell Group institutions, including KingsCollege London, Bristol, Sheffield, Leeds,Nottingham, Birmingham, Southampton,Liverpool and Newcastle.

Queen Mary has also excelled in several subjectgroups, being in the top five in many, including(in addition to the medical and dental subjectsitemised on page 1):

• English Language and Literature (ranked 2ndahead of UCL, Oxford and Cambridge)

• Linguistics (ranked 1st ahead of UCL, Oxford and Cambridge)

• Drama, dance and performing arts (ranked1st for Drama, but 2nd equal in the unit ofassessment with the department ahead of us not being entered for Drama)

• Geography (ranked 1st equal with Bristol,Cambridge, Durham and Oxford)

Queen Mary was also ranked in the top 10 in:

• Law

• Russian, Slavonic and East European Studies

• Iberian Languages

• Metallurgy and Materials

• Economics and Econometrics



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Our Education Mission

Barts and The London offers an innovative and distinctive educational experience to our2,300 undergraduate and 1,000 postgraduate students, which we believe to be quitedifferent to and richer than other London medical schools.

We offer our students exposure to research and clinicalenvironments with worldwide reputations; the exceptionallyrich cultural and social diversity of east London; and avaried and innovative mixture of educational opportunities to accommodate different learning styles.

Because of the distinctively complex health environmentthat characterises the communities served by the School,combined with the excellence of our research, academicand clinical activity, we are able to produce outstandinggraduates who go on to great success in their careers.

Our students develop into scientifically-based clinicians with the highest quality clinical skills and professionalcompetencies, who are also compassionate leaders ofhealthcare delivery across the full range of clinical activityand who are confident and self motivated individualspossessing key skills for lifelong personal development.

We have many distinctions and successes in education.

• Outstanding results scored in recent teaching qualityassessments

• Our Medical degree course achieved top scores in areas of teaching, curriculum, student support andlearning facilities

• Our Dental degree course was one of the few in the country to achieve a maximum score of 24 forteaching quality

• A very positive recent General Dental Council report

• The only Centre of Excellence for Teaching and Learning(CETL) awarded in London by HEFCE, investment of£3.15 million with City University in recognition ofexcellence in training 3,000 healthcare professionalsacross six disciplines

• Barts and The London was one of the pioneer medicalschools to offer a Medical Graduate Entry Programme,now also in Dentistry

The School has introduced an innovative newundergraduate curriculum. Key features of the revised“Curriculum ’08” include an increased emphasis on thescientific basis of medical practice and the development of medical professionalism. Other features include astrengthening of the much valued integrated systems-basedapproach to learning, whilst retaining an emphasis on thedevelopment of excellent clinical and communication skills.The course aims to provide the School’s students with arange of core and self-selected learning opportunities inboth hospital and community settings and includesinterdisciplinary modules as well as a choice of projects and electives abroad.

The School’s students are highly motivated, with their ownautonomous Association (within the Queen Mary’s Students’Union) headed by a sabbatical Student President. Inaddition to the usual sports, drama and special interestclubs and societies, the Association has developed closelinks with the local community, examples being the raisingof funds to build and run a residence for students andelderly people to live and work together and the running of a ‘Teddy Bear Hospital’ scheme with local schools.

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Our Clinical Engagement

Barts and The London School of Medicine and Dentistry hashighly productive relationships with all NHS Hospital Trustsand Primary Care Trusts in North East London.

We are proud of our association with Barts and The London Trust, which wasranked as the country’s top teaching hospital in the Healthcare Commission’sAnnual Performance Ratings in 2007. The £1 billion PFI redevelopmentprogramme at the Royal London Hospital, Whitechapel and at Barts – the largesthospital building project in Europe - will provide a world-class environment forthe School’s teaching and research activities.

We were the first Medical School and NHS Trust in the UK to develop jointClinical Academic Units to exploit synergies between the School and The Trust in the following specialities:

• Cancer

• Circulatory and Metabolic Sciences

• Digestive Diseases

• Dentistry and Oral and Maxillo-facial Surgery

• Musculoskeletal

• Anaesthesia and Critical Care

• Neurosciences

• Trauma

• Acute and Emergency Medicine

• Paediatrics

• Women’s Health

• Cutaneous Medicine and Surgery

• Clinical and Laboratory Sciences

• Infection and Immunity

• Patient Services


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The biggest and most research active of theClinical Academic Units are led by seniormedical school staff, again demonstrating theclose strategic relationship between Trust andSchool.

In 2006 the UK Clinical Research Network andthe Department of Health appointed eight LocalResearch Networks to support the delivery andconduct of clinical diabetes research. Thenetwork covering north east London is led byProfessor Graham Hitman. It promotes researchthat will improve care for people with diabetes,aiming to increase public and patientinvolvement in diabetes research, andsupporting workforce development. Areascovered by the North East London Networkinclude: Barking & Dagenham; City & Hackney;Havering; Newham; Redbridge; Tower Hamlets;and Waltham Forest. It is based at Barts andThe London NHS Trust.

The School has a strong commitment toproviding the leading contribution to the NHSskills and education agenda across North EastLondon and beyond into the Thames Gateway.Close relationships have been developed withHomerton, Newham, Whipps Cross, Queen’s(Romford) University Hospital Trusts. Strongworking links have been developed with thePrimary Care Trusts in north east London.

Dentistry also has links further afield inSouthend, Essex, where it has established aninnovative dental outreach centre, as well as ineast London where another outreach clinic hasbeen established on the Isle of Dogs.

To strengthen the impact of our education andskills contribution to our communities, we arecurrently planning an innovative partnership,North East London Health, that will bringtogether education and training provision acrossHospital and Primary Care Trusts in the sub-region and will be a partnership between thesebodies and The Barts and The London Schoolof Medicine and Dentistry, with City University,the University of East London and LondonSouth Bank University.


Redevelopment of the Royal London Hospital (artist’s impression)


Our Research Excellence

Over the past five years Barts and The London School of Medicine and Dentistry has been transformed into one of the top research institutions in the UK. Highlights includecharacterising susceptibility genes for complex diseases such as hypertension, diabetes and coeliac disease; identifying the genes responsible for Harlequin Ichthyosis; showing thatstem cells can regrow liver, pancreas and intestine; the production of the Down’s syndromemouse; showing that breast cancer screening reduces mortality; producing the evidence that folic acid should be added to bread in the UK, as happens in 31 other countries; andshowing that vitamin D boosts immunity to tuberculosis


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Barts and The London School of Medicine and Dentistry hasshown the largest increase in research funding in the last fiveyears in the UK. The School has the highest amount of blue-chip charitable income in the UK, and our research spend in 2006-7 placed us 11th in the Russell Group of medicalschools. Our 2007-8 spend of £41.5 million represents a 20per cent year-on-year increase, the highest in the UK, andmoves us to 7th overall. Our current portfolio of 1001 awardstotals £125 million, including seven programme grants fromthe MRC, seven programme grants from Wellcome Trust, and12 programme grants from Cancer Research UK. Among oursenior investigators, 90 per cent have at least one paper withgreater than 100 citations and 14 of our senior researchershave, in total, an astonishing 309 papers with greater than100 citations and individual “H factors” between 50 and 81.

The School’s translational research strength has beenrecognised by, amongst others, the award of a NIHRBiomedical Research Unit in Cardiovascular Disease, with a £5.375 million grant awarded in 2008 to Barts and TheLondon School of Medicine and Dentistry, and Barts and The London NHS Trust.

More than 25 world-class researchers have been appointedat Professorial level since 2005, along with 50 new groupleaders (Lecturers and Senior Lecturers).

The 2008 Research Assessment Exercise results showedBarts and The London School of Medicine and Dentistryjoining Oxford, Cambridge, Imperial College and UniversityCollege London in the top 5 research-active medical anddental schools in England.

According to ranking published in the Times HigherEducation, Barts and The London scored consistently in the top five:

• Dentistry was ranked 1st equal with Manchester based on3* and 4* outputs, and 2nd overall out of 14 UK dentalschools.

• In Cancer, we were ranked 3rd out of 14 submissions interms of 3* and 4* outputs and joint 5th in the UKoverall, ahead of Oxford, Imperial, Kings College Londonand University College London

• The Institute of Cell and Molecular Science, returned inHospital Subjects, was ranked joint 1st with Cambridgeand Edinburgh in terms of 3* and 4* outputs and wasjoint 7th overall out of 28, ahead of Manchester,Newcastle and Southampton.

• The Wolfson Institute of Preventive Medicine, returned in Epidemiology and Public Health, was 2nd out of 21 in terms of 3* and 4* outputs, and 3rd overall, ahead of Oxford, University College London and Bristol

• In Health Services Research, we were ranked 4th overallout of 28, ahead of Oxford, University College London andKings College London

• The William Harvey Research Institute, returned inPreclinical and Human Biological Sciences, was ranked3rd in terms of 3* and 4* outputs, and 4th overall out of13, ahead of Kings College London, Bristol andNottingham.


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Malcolm Alison Professor of Stem Cell BiologyQasim Aziz Professor of NeurogastroenterologyDavid Baker Professor of NeuroimmunologyDavid Beach Professor of Cell BiologyInderjeet Dokal Professor of HaematologyMarco Falasca Professor of Signal TransductionGavin Giovannoni Professor of NeurologyJohn Gribben Professor of Experimental Cancer MedicineJonathan Grigg Professor of Paediatric Respiratory

and Environmental MedicineIan Hart Professor of OncologyDavid van Heel Professor of Gastrointestinal GeneticsLouise Jones Professor of Breast PathologyAjay Kakkar Professor of Surgical SciencesAnia Korszun Professor of PsychiatryAttila Lorincz Professor of Molecular Epidemiology

Tom MacDonald Professor of ImmunologyIan MacKenzie Professor of Stem Cell ScienceNic Maffuli Professor of Sports MedicineSilvia Marino Professor of Neuro-oncologyAine McKnight Professor of Viral PathologySussan Nourshargh Professor of Microvascular PharmacologyKen Parkinson Professor of Head and Neck CancerJohn Pasi Professor of Haemostasis and ThrombosisCostantino Pitzalis Professor of Experimental RheumatologyRay Playford Professor of GastroenterologyDenise Sheer Professor of Human Genetics Andrew Silver Professor of Cancer GeneticsKen Suzuki Professor of Translational

Cardiovascular TherapeuticsBart Vanhaesebroeck Professor of Cell Signalling

Selected Professorial Appointments made in the past five years


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Charterhouse Square Campus

In addition to new senior staff, Barts andThe London is placing particular emphasison recruiting young researchers andsupporting them to become stars of thefuture. You can read about some of themlater in this brochure.

The School has a fully-integrated JointResearch Office with Barts and TheLondon NHS Trust which takes care ofgrant administration and, increasingly, isproviding academics with assistance in the more complex types of proposals, such as EU FP7.

Our Principal Investigators have protectedresearch time in order to maximise theirproductivity and are co-located into

research centres and environments ofcritical mass underpinned by state-of-the-art core facilities in: Genomics; FunctionalGenomics; Proteomics: Imaging,Transgenic and Knockout mouse unit; and Structural Biology. A core Genomicsand Proteomics Centre has been fundedby the Barts and The London CharitableFoundation (£3.1 million includingrefurbishment). This Centre provides state-of-the-art facilities to support the School’sgenomic and proteomics researchprogrammes and associated bioinformatics.

The recruitment of new high profile staffand the nurturing of our young researchershas led to a significant increase in thenumber of papers in world-class journals,

which increased from two in RAE 2001 to124 in RAE 2008. We have seen a similarlarge increase in the number of MRCTraining Fellows and Senior Fellows (27 intotal). Some 200 researchers in the Schoolwere assessed for RAE 2008 and judgedby external review to be producing highinternational quality research.

Each of the School’s Institutes has beendesigned to co-locate congruent groups of research centres sharing commonresearch goals, techniques andinfrastructure, including materials,technical support and equipment and to provide maximum opportunity forinteraction and co-operation with therelevant clinical activity.



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On the Charterhouse Square Campus, theSchool aims to deliver an internationallyrecognised centre of excellence inCardiovascular and Cancer research, which will directly complement the clinicalservice delivery on the St Bartholomew’sHospital site. Three Institutes are based in Charterhouse Square: the Institute ofCancer; the William Harvey ResearchInstitute, majoring in cardiovascularresearch, genetics, pharmacology andendocrinology; and the Wolfson Institute ofPreventive Medicine, majoring in molecularepidemiology and public health.

The William Harvey Research Instituteoffers a vibrant, fully integrated clinical and basic science environment devoted to understanding basic pathogenicmechanisms and therapeutic innovation in cardiovascular, inflammatory andendocrine diseases. Since 2001 WilliamHarvey investigators have published in high impact journals such as Nature,Nature Genetics, Nature Biotechnology,The Lancet, Circulation, Journal ofExperimental Medicine and the Journal of Immunology, and spent over £33 millionon research. These successes have led tothe William Harvey being ranked amongstthe top 20 pharmacological researchinstitutions in the world based uponcitations (according to The Scientist,2004).

The Institute of Cancer was founded in 2003 and under the leadership ofProfessor Nick Lemoine has rapidlydeveloped into one of the leading centresin Europe. In Spring 2004 the Schoollaunched a Cancer Research-UK ClinicalCentre on this campus, the first CR-UKclinical centre in the UK. In 2007 it hosted,in collaboration with the University ofCambridge, the CR-UK MolecularPathology Training Programme. Also in2007, with funding from the Department of Health, the Institute was awarded £2million to establish the first ExperimentalCancer Medicine Centre, to fast-track newcancer treatments. It is led by ProfessorJohn Gribben and Professor Nick Lemoine.

The Wolfson Institute of PreventiveMedicine at Charterhouse Square housessome of the most renowned figures inpublic health worldwide. Led by ProfessorSir Nicholas Wald FRS, it has producedground-breaking research on screening for Down’s syndrome, the role of folate in the prevention of spina bifida, and the ability of the “polypill” to reducedramatically cardiovascular disease andstroke. The Cancer Epidemiology group, led by Professor Jack Cuzick, is a worldleader in cancer prevention and among its achievements is showing that breastscreening reduces mortality from breastcancer.

The John Vane Building which housesmost of the research staff at CharterhouseSquare has undergone completemodernisation in the last three years, and a new Heart Centre is currently underconstruction which will be complete in2009.

On the Whitechapel Campus, a newlandmark architecturally distinguishedbuilding for research into cell andmolecular science opened in April 2005(the Blizard Building). This exciting capitaldevelopment houses the Institute for Celland Molecular Science (ICMS), withlaboratory and office accommodation for400 research workers in disciplines whichmatch the local clinical activities of TheRoyal London Hospital. The ICMS includesresearch centres of excellence in SkinDisease, Immunology and InfectiousDisease, Gastroenterology, Surgery,Paediatrics, Diabetes and Neurosciences.

A key feature of the design of the newbuild is the large open-plan laboratory and office accommodation which aims toensure maximum flexibility and interactionbetween the research workers of the ICMS.A key element of the School’s investmentstrategy for this Institute is to encourageinter-disciplinary research through thedevelopment of themes which link multiplecentres and thereby gain synergistic value.

Another major development at Whitechapelis the QM Bioenterprises building,scheduled to open in 2009, adjacent to theBlizard Building, which will provide 40,000square feet of space for small to mediumbioscience companies. This will beavailable for QM researchers wishing tocommercialise their research as well asthose from other institutions. An excitingfeature of this development is the web-based portal which will allow prospectiveclients and entrepeneurs to design andcost facilities on-line. The School is alsoredeveloping other sites to house theCentre for Health Sciences, to driveforward our primary care research agendain the unique health care setting of eastLondon, with its large immigrantcommunities.

Our research strengths are:

• translation of basic research into man

• cancer

• cardiovascular

• dentistry

• inflammation

• endocrinology/metabolism

• immunology and infectious diseases

• skin disease

• genomics

• neuroscience

• gastroenterology

• epidemiology

• public health and primary care

These are grouped in the rest of thisbrochure under the headings of:

• Cancer

• Stem Cells

• Genetic Basis of Common and Rare Diseases

• Infection, Inflammation and Repair

• Neuroscience

• Dentistry

• Preventive Medicine and Public Health

Our Research Excellence (cont)


Professor of Cell Signalling,Bart Vanhaesebroeck

see profile p16


Cancer

Cancer research is a leading strength of Barts and The London School of Medicine andDentistry. World-class research into the disease at Barts and The London is being pursued in:

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• Institute of Cancer

• Wolfson Institute of Preventive Medicine

• Institute of Cell and Molecular Science

This concentration of expertise makes Barts and TheLondon one of the most significant power-houses of cancer research in Europe, and many investigators holdprogramme awards from CRUK and other funders.

In Cancer, in the 2008 Research Assessment Exercise, wewere ranked 3rd out of 14 submissions in terms of 3* and4* outputs and joint 5th in the UK overall, ahead of Oxford,Imperial, Kings College London and University College London.

The Institute of Cancer, led by Professor Nicholas Lemoine, has been the focus for substantial new investment in basic,translational and clinical cancer research over the past fiveyears. The Institute represents one of the largest cancerresearch bodies in the UK with a total of 300 staff, raisingsome £45 million in grant income over the past five years,with £12.6 million spent in 2006/7 alone.

Research in Cancer at Barts and The London is built on anintegrated molecular and cellular approach to the problemof cancer in individuals and in populations.

Research strengths represented include:

• therapeutic and diagnostic target identification and validation in both haematological and solidmalignancies

• clinical trials exploring new therapies

• the development of novel molecular approaches for diagnosis, classification and treatment of humancancers

• investigations into the regulation of tumour spread and host anti-tumour responses.

Facilities and Clinical EnvironmentInstitute of Cancer researchers are housed in anoutstanding research environment on the CharterhouseSquare campus, with significant investment from QueenMary, the MRC and charities into new laboratories as well as new staff appointments. An extensive Infrastructureprogramme has provided state-of-the-art laboratories andoffices. This working environment is multidisciplinary andwell-resourced, promoting academic exchange andtranslational research at all levels.

The Institute is also home to many of the laboratories of the Cancer Research UK Clinical Centre at Barts and The London. This was the first centre of its kind to beestablished and is one of the largest constellations of Cancer Research UK clinical and translational groups in the UK university sector.

Cancer research at Barts and The London takes place closeto the clinical care facilities for oncology at Barts Hospital.Barts was the first Clinical Cancer Centre recognised byCancer Research UK and has been supported since 2004by over £1.2 million per year of infrastructure funding. Thiswas followed by the creation of the Centre for ExperimentalCancer Medicine funded by a £2 million grant from theDepartment of Health and CR-UK, which providesinfrastructure for translational research, from early to latephase clinical trials.

The configuration of the Barts Hospital site as aComprehensive Cancer Centre, to be completed in 2011 as part of Barts and The London’s £1.3 billion hospitalredevelopment, the largest in Europe, will provideoutstanding facilities for clinical research.



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Cancer research themes at Barts and The LondonMolecular Oncology and Imaging is an internationally recognised centre ofexpertise in gene therapy for cancer, with an active programme of clinical trials,as well as programmes for the identification of molecular biomarkers of diseaseprogression and treatment response. It houses the state-of-the-art molecularimaging facilities for both preclinical and clinical studies.

Cancer and Inflammation focuses on the link between cancer and inflammatoryresponses, in particular the role of immune cells and mediators found inexperimental and human cancers.

Cell Signalling is a world-class centre of expertise in both basic and applied PI3Ksignalling research. The programme focuses on the way in which uncontrolledPI3K signalling is one of the most commonly deregulated pathways in cancer.

Experimental Cancer Medicine focuses on early phase trials of novel therapeuticsdeveloped in the Institute of Cancer, as well as recruitment into late clinical trials,including NCRN, pharma-sponsored and investigator-initiated clinical trials openat Barts and The London NHS Trust.

Some leading Barts and The London Cancerresearchers

Professor Nicholas Lemoine is the Director ofboth the Institute of Cancer and the CancerResearch UK Clinical Centre. He also leads theCentre for Molecular Oncology & Imaging, wherethe research of four groups focuses on themolecular pathology of solid malignancies, genetranscription biology, cell survival signalling, andmolecular therapeutics including gene therapyand vaccine approaches.

Professor Jack Cuzick (Wolfson Institute ofPreventive Medicine), leads research into thescreening and prevention of cancer. Key areasof interest are cancers of the breast, uterinecervix, prostate and colon. In these areas thereare activities encompassing prevention studies,screening studies, treatment comparisons,prognostic factors for survival, and aetiologicalstudies of risk factors for developing malignantdisease.

Professor Frances Balkwill’s work has led to therealisation that cancers possess a complexcytokine network, that a pro-inflammatorytumour micro-environment is involved in tumourpromotion and spread, and that there are stronglinks between the processes of chronicinflammation and cancer.


Professor Jack Cuzick

Cancer (cont)


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Professor Bart VanhaesebroeckMSc, PhDCentre Lead, Cell Signalling

Professor Bart Vanhaesebroeck joined the Institute of Cancer at Barts and TheLondon School of Medicine and Dentistryfrom the Ludwig Institute for CancerResearch (University College London), to set up the Centre for Cell Signalling inJune 2007.

His research group’s key interest lies inunderstanding signalling through PI 3-kinases (PI3Ks), combining fundamentalresearch with efforts to translate findingsinto diagnostic and therapeuticapplications.

In previous work, the team proposed thenow universally accepted classificationand nomenclature of the PI3Ks(Philosophical Transactions of the Royal

Society of London 1996:351:217, TiBS1997:22:267). They cloned the p110deltaisoform of PI3K (PNAS 1997:94:4330),revealed p110delta-selective functions incells (Nature Cell Biology 1999:1:69;Cancer Res 2003:63:1667) andgenerated mouse models to investigatethe in vivo function of this enzyme. Theyhave pioneered the use of so-called'kinase knockin' mice in which the activesite carries a mutation in an ATP-bindingamino acid residue, leading to inactivationof the kinase. These provide a moreadequate physiological model for theeffects of small molecule kinase inhibitorsthan classical gene knockout approaches(Cell 2004:118:274; TiBS 2005:30:194).Their recent studies have revealed keyfunctions for p110delta PI3K in adaptiveimmunity (Science 2002:297:1031),allergy (Nature 2004:431:1007) andleukaemia (Oncogene 2006:25:6648).Partly through these research efforts,p110delta has become a drug target incancer, inflammation and auto-immunity.These discoveries were successfullyincorporated into the drug developmentprogramme of Piramed and is now furtherdeveloped by Roche. Application of themouse knockin strategy has furtherallowed the team to uncover the firstphysiological roles of the p110alpha(Nature 2006:441:366, Nature2008;29:453) and p110beta (PNAS2008:105:8292) isoforms of PI3K. Theteam is also developing novel

methodologies to monitor the amount andactivation of signal transduction enzymes,with focus on the PI3K pathway (PNAS2006:103:8959, PNAS 2007:104:7809).

Bart studied at the University of Ghent,Belgium, gaining a Masters degree(1985) in Biology (Physiology andBiochemistry) and a PhD (1990) inMolecular Biology. His PhD work,supervised by Drs. Walter Fiers andJohan Grooten, focused on immunologyand signal transduction by cytokines. Hethen had to fulfil his military service whichhe carried out while working at UniversityHospital in Ghent in the Laboratories ofToxicology and Immunology. Followingpostdoctoral studies on signaltransduction by Tumor Necrosis Factor, in the Laboratory of Molecular Biology inGhent, and a brief stay at the Universityof Padova, Italy (with Professor TulioPozzan), he joined Mike Waterfield'sgroup at the Ludwig Institute for CancerResearch in 1993 to work on PI 3-kinases. Since 1998, he has headed theCell Signalling Group at the LudwigInstitute for Cancer Research, in 2000,was appointed as a Lecturer, and in 2005as a Professor at the Department ofBiochemistry and Molecular Biology atUniversity College London. Bart is amember of EMBO (European MolecularBiology Organisation) and has been aconsultant for Serono (Geneva), PIramed,AstaZeneca and Intellikine.

Cancer (cont)



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Cancer research themes at Barts and The London (cont)Medical Oncology has a long and distinguished history in haemato-oncology,urological and paediatric malignancies, having led several pivotal trials in thetreatment of these cancers.

Tumour Biology is concerned primarily with understanding the role thatcytoadhesion plays in modulating cancer spread and has focused particularly on the involvement of members of the integrin family of adhesion receptors.

The Institute of Cancer has strong links with the Wolfson Institute for PreventiveMedicine, in particular Professor Jack Cuzick’s randomised cancer preventiontrials: the international IBIS-II breast cancer prevention trial (determining whetherthe aromatose inhibitor anastrozole has greater preventive effect than tamoxifen,with fewer adverse effects of treatment including thromboembolism); the CRISP-Itrial of diindolymethane in women with mildly dyskaryotic smears in theprevention of cervical cancer; and the UK trial of chemo-prevention ofendometrial cancer in genetically susceptible women (POET). The WolfsonInstitute is the leading UK centre in the HPV vaccine trials sponsored by Glaxo-Smith-Kline.

Some leading Barts and The London Cancerresearchers (cont)

Professor John Gribben leads the newlyestablished Centre for Experimental CancerMedicine. The main objective of the Centre is to provide a centre of excellence to facilitatetranslational cancer research from basicscientific discovery to the delivery of novelapproaches to care of patients with cancer.

Dr Claude Chelala’s research focuses on thedevelopment and application of computationalsolutions to cancer research including thedesign and implementation of a generic modelfor the organisation, integration and mining ofcomplex data for cancer research.

Dr Thorsten Hagemann’s major research focus isto understand the fundamental mechanisms bywhich TNFα signalling promotes cancer; withparticular reference to the role of macrophagesand their phenotype in carcinogenesis.


Cancer (cont)

Professor John Gribben


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Professor Iain McNeishMA PhD MRCPMRC Senior Clinical FellowProfessor of Gynaecological Oncology and Honorary Consultant in Medical OncologyDeputy Director Centre for Experimental Cancer MedicineCentre for Molecular Oncology and Imaging

Professor McNeish joined the Instituteof Cancer in May 2004. He trained inmedicine at Oxford and did his PhD at

the Institute of Cancer Studies at theUniversity of Birmingham. From 1998 to2004, he combined training in medicaloncology at Hammersmith and CharingCross Hospitals with post-doctoralresearch at the Molecular Oncology Unit at Imperial College. The focus ofhis research is ovarian cancer, also hisclinical sub-specialisation. His researchprogramme focuses on abnormalities inapoptosis and cell cycle control inovarian cancer as a target for gene andviral therapy. In particular, his group isstudying the therapeutic potential ofselectively replicating adenoviral vectorsas therapy in ovarian cancer, and aphase I trial of one such virus, VTP1(dl922-947) will shortly commence inthe new Centre for Experimental CancerMedicine Unit, which launched inSpring 2008. Further, his group isstudying the mechanisms by whichreplicating adenoviral vectors inducecell death and whether this can beaugmented with apoptosis inducers,such as chemotherapy or pro-apoptoticgenes. His group is also looking at

methods of imaging viral activity in whole organisms usingbioluminescence, fluorescence and PET imaging.

Most recently, Professor McNeish wasawarded an MRC programme grant andSenior Clinical Fellowship, worth £1.7million over 5 years, to continue hisresearch on replicating adenoviruses. In particular, the Adenoviral EIA deletion mutant dl922-947 seems towork well in partnership with paclitaxel,a chemotherapy drug commonly used in ovarian cancer, but it is important to understand why, and whether otherchemotherapy drugs may also combinewell. The programme also seeks tounderstand how the immune systemresponds to dl922-947 in the abdominalcavity, where ovarian cancer grows.Finally, the reasons why some ovariancancer cells do not respond well todl922-947 will be explored, by studyingthe patterns of gene expression insensitive and resistant cells, especiallygenes that control cell division.


Cancer (cont)


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Professor of Stem Cell Science, Ian McKenzie


Stem Cells

Given their unique ability to replicate specific human cells and tissues, and their potential to cure disease and heal injury, the study of stem cells is a keycomponent of the School’s research strategy.

The School has teams working on internationally competitive research programmes in areas such as adultstem cell plasticity, stem cell re-differentiation and trans-differentiation cancer stem cells, bioreactors and stem cell amplification, and stem cell targeting. These programmes were brought together by the Initiative in Stem Cell Biology established by the School in 2006, with funding from Barts and The London CharitableFoundation.

Designed to promote cross-collaborative research and to advance discoveries in this important field, theInitiative includes all the research centres within the Institute of Cell and Molecular Science, as well as theInstitute of Cancer, the Institute of Dentistry, the William Harvey Research Institute, and bioengineeringresearchers based in the School of Engineering and Materials Science at Queen Mary.

The Institute of Cell and Molecular Science, returned in Hospital Subjects, was ranked in the 2008 ResearchAssessment Exercise joint 1st with Cambridge and Edinburgh in terms of 3* and 4* outputs and was joint 7thoverall out of 28, ahead of Manchester, Newcastle and Southampton.

Research programmes investigate various aspects of stem cell biology, ranging from basic science to clinicalapplication, and many of these studies have already made a significant scientific contribution. Research aimsto answer key questions such as whether differentiated cells can revert to the stem cell phenotype, which adultstem cells are tissue specific and which can transit to other tissues via the circulatory system. An example ofthis is the work of Professor Sir Nicholas Wright who, with colleagues, demonstrated that hepatocytes (livercells) can be produced from non-hepatic adult stem cells.

Researchers in the The Centre for Cutaneous Research identified a number of key stem cell molecules that are important in epidermal differentiation, wound healing and signalling between hair follicles and the epidermis.

Other ongoing investigations include identifying stem cell marker proteins and determining the specific cellularcues (known as homing and cell fate signals) that form the correct microenvironment for cell regeneration.These include gene encoding growth factors and developmental genes.

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Stem Cell Research (cont)

Well established stem cell groups within the Institute of Cell and Molecular Science and the William Harvey Research Institute include:

• Intestinal stem cells

• Heart stem cells

• Epithelial stem cells

• Malignant stem cells

• Pancreatic stem cells

• Haemopoietic stem cells

• Hair stem cells

• Genetics of stem cells

• Mesenchymal stem cells

• Neural stem cells

• Embryonic stem cells

• Inherited stem cell disorders

Some leading Barts and The London Stem Cell Researchers

Professor Ken Suzuki’s current work primarily focuses ontranslational research on stem cell therapy for treating heartfailure using stem/progenitor cells with the firm aim ofestablishment of this therapy in the clinical arena. His work aimsto understand stem cell therapy and refining current protocolswhich can help myocardial inflammation and regeneration, andmyocardial protection against ischaemia-reperfusion injury usinggene therapy and advanced technologies

Professor Ian Mackenzie, whose research interests are thecellular mechanisms involved in the maintenance of skin and oral mucosa; stem cells; tissue renewal; and cancer.

Professor Mike Philpott, who works on the role of stem cells inhair renewal.

Professor Silvia Marino, who has published ground-breakingwork on the role of neural stem cells in neuroblastoma.

Professor Malcolm Alison who specialises in research into stemcell biology of the pancreas, liver and gastrointestinal tract.During the course of his work he has developed novel methodsfor lineage tracing in human tissue, specifically in liver andpancreatic stem cells, with particular reference to diabetes, end-stage fibrotic disease and cancer.

Professor David Beach FRS has a long-standing interest in themechanism of cell cycle control and its role in inhibiting thegrowth of cancer cells. He discovered the relationship betweencyclins and cyclin-dependent kinases, specifically the tumoursuppressor genes p21 and p16, and has more recently focusedon the problem of cellular life span control, an extension of hiswork on cell cycle regulation.

Professor Inderjeet Dokal has identified the role of telomeraseand associated genes in the pathogenesis of the stem cellsdisorders which underlie aplastic anemias.

Dr Anthony Mathur, William Harvey Research Institute, along withProfessor John Martin, from University College London, runs apioneering research project testing the ability of stem cells toreduce the number of fatalities among heart attack patients andto improve heart function after the event.

In keeping with the strategy of the Institute ofCell and Molecular Science to gain synergisticvalue through the development of inter-disciplinary themes, in 2006 the Initiative in Stem Cell Biology was launched whichtraverses each of the component ResearchCentres within the Institute and extendsbeyond to incorporate researchers from other Queen Mary Departments (e.g. Bio-engineering) and linked Institutes (e.g.Institute of Cancer). The aim of the Initiative is to consolidate and expand an internationallycompetitive research programme in areasincluding adult stem cell plasticity, stem cellre-differentiation and trans-differentiation,bioreactors and stem cell amplification, andstem cell targeting.

The initiative is headed by Professor IanMacKenzie.


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Emma SmithPhD studentCentre for Cutaneous Research

“I chose to come to Barts and The London School of Medicineand Dentistry partly because of the fantastic modern facilitiesat the Institute of Cell and Molecular Science (ICMS), it'sexciting coming to work everyday in the space-agey Blizardbuilding! Also there is a great sense of community here -everybody is very friendly and enthusiastic.”

Professor of Stem Cell Biology, Malcolm Alison


Genetic Basis of Common and Rare Diseases

Barts and The London has one of the most significantgroupings of medical genetic researchers, seeking to findand study the genetic causes of human diseases; includingskin disease; diabetes; coeliac disease; obesity; Down’ssyndrome; cancer; motor-neurone disease; hypertension,and heart disease.

In the 2008 Research Assessment Exercise, the Institute of Cell and MolecularScience, returned in Hospital Subjects, was ranked joint 1st in the UK withCambridge and Edinburgh in terms of 3* and 4* outputs and was joint 7th overall out of 28, ahead of Manchester, Newcastle and Southampton.

The William Harvey Research Institute, returned in Preclinical and HumanBiological Sciences, was ranked 3rd in terms of 3* and 4* outputs, and 4thoverall out of 13, ahead of Kings College London, Bristol and Nottingham.

Hypertension and Heart DiseaseThe aims of research in this area are to understand the basic underlyingpathogenic mechanisms associated with the initiation and development of vascular diseases, eg, atherosclerosis and hypertension. Professor MarkCaulfield, director of the William HarveyResearch Institute is a pre-eminent figurein the genetics of cardiovascular disease.He is national co-ordinator of the MRCBritish Genetics of Hypertension Study.With Dr Patricia Munroe he co-ordinatesthis study on behalf of five other UKuniversities (Aberdeen, Cambridge,Glasgow, Leicester and Oxford). Hepublished the largest genome screen in human hypertension on 2010 sib pairs highlighting four regions that may harbour susceptibility genes for essentialhypertension in The Lancet during 2003. The BRIGHT study is an activemember of the MRC Human Sample Collection Initiative. With the WellcomeTrust Case Control Consortium, BRIGHT is partnering Oxford, Cambridge and theSanger Centre to undertake pathfinder experiments for genome-wide association.Professor Caulfield is co-grant holder with Imperial, Cambridge and Oxford on theWellcome Trust Functional Genomics Programme (£5.4 million) to developobservations on metabolic syndrome and translate these from experimentalmodels to man. Professor Caulfield is also Deputy Chair of the London BiobankRegional Collaborating Centre and a member of Biobank UK Sample StorageCommittee, Chair of Biobank UK Ethnicity Sub-Group, member of Biobank UKMeasurement Sub-Group.


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Professor of Clinical Pharmacology,Mark Caulfield


Professor of Molecular Medicine and Diabetes, Graham Hitman


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Skin diseasesThe main focus is hyperproliferative skin diseases such as the palmoplantarkeratodermas (PPK) and ichthyoses.Professor David Kelsell’s team in theInstitute of Cell and Molecular Science has identified the important role of proteinsinvolved in the regulation and formation of epidermal cell junctions responsible for cell-cell adhesion, cell signalling andcommunication, key properties to maintainthe normal cellular phenotype and tissuearchitecture.

Additional research programmes includethe investigation of genetic and molecularevents occurring in Basal Cell Carcinoma.

A prominent success which has received extensive media attention is the identification of the gene that causes the debilitating skin condition HarlequinIchthyosis. Many children born with thedisease die within two days of birth: thosethat survive endure painful rituals ofscrubbing and applying cream to their skinat intervals to prevent it from cracking andbecoming infected. The research group’sfindings will facilitate the prenatal DNAdiagnosis of this life-threatening disorder,and also pre-implantation genetic testing.With further research, more effectivetreatments could also be designed forHarlequin children.

Diabetes and periodic feversBarts and The London is at the forefront of the international gene discoveryprogramme in diabetes, related disorders,and periodic fevers (including genome-wide association scans, candidate genes,functional genomics and appliedphysiology) and can count among itsachievements a number of seminaldiscoveries. Research is led by ProfessorGraham Hitman and an exciting newdevelopment is the recruitment of DrVardhman Rakyan to bring his ground-breaking work on epigenetics into ourresearch portfolio.

The current research programme focuseson genes important to inflammation andpancreatic beta cells in a number of majorresources including British/Irish as part ofthe Diabetes UK/MRC Warren2 collections,and from the South Asian subcontinentincluding younger adult patients fromBangladesh. The cell biology links to thegenetic work with major interests inpancreatic beta cell metabolism and insulinsecretory granule trafficking. Researchershere recently discovered that calpain-10 isa trigger for insulin release; current studiesare extending to actions on thecytoskeleton and into other endocrine celltypes.

The strength and uniqueness of thisresearch is the clinical focus of the work,spanning from basic science to clinicalapplication. An emerging interest is in theprevention of diabetes that is especiallyrelevant to the School’s local Whitechapelcommunity. Clinical translational researchthat interfaces with the NHS has beenstrengthened by several initiatives includingthe setting up of the North East LondonLocal Diabetes Research Network (co-ledby Graham Hitman) and a recent award of an MRC, National Prevention ResearchInitiative grant to pilot methods foridentification of people at risk of diabetesand prevention strategies in the localBangladeshi population.

ObesityProfessor Graham Hitman was among a team of scientists to have identified agenetic link to obesity through a genome-wide study of 2,000 people with type 2 diabetes and 3,000 controls. This study was part of the Wellcome Trust Case Control Consortium, one of thebiggest projects ever undertaken to identifythe genetic variations that may predisposepeople to or protect them from majordiseases. Through this genome-wide study, the researchers identified a strongassociation between an increase in bodymass index (BMI) and a variation, or

"allele", of the gene FTO. Their findingswere published in the journal Science.

The study found that people carrying one copy of the FTO allele have a 30 per cent increased risk of being obesecompared to a person with no copies.However, a person carrying two copies of the allele has a 70 per cent increasedrisk of being obese, being on average 3kg heavier than a similar person with no copies. Amongst white Europeans,approximately one in six people carry both copies of the allele.

Coeliac diseaseResearch led by Professor David van Heelhas recently identified eight new geneticrisk factors for coeliac disease - a diseaseaffecting one in 100 of the population -which is caused by an excessive immuneresponse to wheat in the gut wall. Fundedby the charity Coeliac UK, and theWellcome Trust, and published in NatureGenetics, the studies have revealed thatthose suffering have a different spectrumof genetic risk variants in multiple genesthat control the nature of the immunesystem response.

Behind its success is the Human GenomeProject - a massive international researchproject to reveal the entire sequence ofgenes of all the human chromosomes.Exploiting technological advances that haveenabled comparison of variations acrossthe human genome in large numbers ofpeople, researchers studied over seventhousand individuals with and withoutcoeliac disease, amongst British, Irish and Dutch populations.

One of the key findings is that healthyindividuals more often have a protectiveDNA sequence in the interleukin-2 andinterleukin-21 gene region than individualswith coeliac disease. Interleukin-2 andinterleukin-21 are cytokine proteinssecreted by white blood cells that controlinflammation. It is likely that the protective


Genetic Basis of Common and Rare Diseases (cont)


DNA sequences leads to different amounts of these cytokines beingproduced providing defence againstintestinal inflammation. Professor Van Heelhas recently been awarded £1 million bythe Wellcome Trust to continue this work.

Down’s syndromeA world leader in Down’s leukaemia researchis Professor Dean Nizetic from the Instituteof Cell and Molecular Science. He is part ofa London based team which achieved agenetic engineering first when it created astrain of mouse with an almost completecopy of chromosome 21. This unusualgenome mimics the genetic makeup ofpeople with Down’s syndrome. The researchwas published in Science.

The modified mouse will make it easier tounderstand the effects of Down’s syndrome,which is linked with types of leukaemia,heart disease and Alzheimer type symptomsrelatively early in life. Researchers havespent over a decade trying to engineer a

Down’s mouse – their efforts complicated bythe fact that the mouse versions of the geneson human chromosome 21 are awkwardlyscattered across three mouse chromosomes.About two-thirds lie on mouse chromosome16, the rest on chromosomes 10 and 17.

Professor Nizetic and his colleagues - alongwith Elizabeth Fisher of the UCL’s Institute of Neurology and Victor Tybulewicz of theMRC’s National Institute for MedicalResearch – rather than trying to duplicateregions of the mouse genome correspondingto human chromosome 21, radically triedinstead to put the human chromosome intomice.

That strain of mice, called Tc1, has about 92per cent of DNA of the human chromosome21. It also has a unique set of severalcharacteristics of Down’s syndrome not seenin any other mouse model. Although thereare no tests for mental retardation in mice,the Tc1 mice have deficits in spatial learningand memory, fewer brain cells with altered

functions, as well as skeletal changes similarto those found in Down’s syndrome patientsand, most significantly, they have heartdefects like those found in Down’s syndromepatients.

The research could have major implicationsin understanding these conditions in peoplewith Down’s and, in the longer term, inaiding efforts to understand and perhapsameliorate other effects of Down’s. Theresearch also has implications concerningcell proliferation, cell differentiation,neurodegeneration, and protection fromcancer, by identifying the molecularpathways and proteins which are altered by trisomy 21. Professor Nizetic’s work issupported by a programme award from the Leukemia Research Fund.

This research has a strong local historybecause Downs syndrome was firstdiscovered at The London Hospital by John Langdon-Down in 1859.

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David van Heel BM BCh MA DPhil MRCPProfessor of Gastrointestinal Genetics

David van Heel was appointed asProfessor of Gastrointestinal Genetics at Barts and The London School ofMedicine and Dentistry, and HonoraryConsultant Gastroenterologist at Bartsand The London NHS Trust, in 2006.He currently holds a Wellcome TrustClinician Scientist Fellowship project,

grant funding from Coeliac UK and aWellcome Trust Programme Grant. His main clinical interests are coeliacdisease and Crohn's disease. Principallyhis research interests lie in the geneticcauses of these diseases, and thefunctional/immunological consequencesof these genetic variants on humanbiology.

David was awarded a Natural SciencesBA at Cambridge University in 1990 and completed Clinical Medicine trainingat the University of Oxford in 1993. A Medical Research Council ClinicalTraining Fellowship led to a DPhil ininflammatory bowel disease geneticsfrom the Wellcome Trust Centre forHuman Genetics, University of Oxford in 2002. He then undertook postdoctoralresearch at Imperial College, andcompleted specialist training as aConsultant in Gastroenterology in 2004.

Research Activity • Identification of disease susceptibility

genes for human intestinalinflammatory diseases (coeliacdisease, Crohn's disease, ulcerativecolitis). A genome wide associationstudy in coeliac disease was publishedin 2007, identifying novel risk factorsin the IL2/IL21 gene region.

• Understanding how genetic variants in disease susceptibility genes lead toaltered biological function and diseasepathogenesis.

• Immunology of Crohn's disease (focus on NOD1, NOD2 and innateimmunity).




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Genome Wide Association Study (GWAS) Professor David van Heel's groupcarried out the first ever coeliac diseasegenome wide association study,published in the journal Nature Geneticsin June 2007. The primary study wasperformed on a British samplecollection, with replication of the majorfinding in a Dutch and an Irish samplecollection.

310,605 single nucleotide olymorphisms(SNPS) were tested for association usingIllumina's chip technology in samplesfrom 778 coeliac disease individualsand 1,422 population controls (British1958 Birth Cohort). Genetic variants inthe IL2 / IL21 gene region wereidentified as risk factors predisposing to coeliac disease.

Genome Wide Association Study Follow UpThe group followed up 1,020 topassociated SNPS from the British GWASin a further set of 1,643 coeliac and3,406 population control samples fromBritain, The Netherlands and Ireland.This study was published in NatureGenetics in March 2008.

They identified seven further generegions predisposing to coeliac disease.There are now nine coeliac gene regionsidentified, including the 2007 IL2-IL21finding and the long-recognised HLA-DQ association. Of the nine regions,eight contain likely candidate genesinvolved in immune system function.This agrees nicely with what is knownabout the immunology of coeliacdisease. It is understood how geneticvariation influences biological functionfor HLA-DQ, and possible mechanismswere reported for two of the newfindings: SH2B3 and IL18RAP.

Interestingly there seems to besubstantial overlap of gene regions withother autoimmune diseases, particularlyfour of the nine coeliac regions alsopredispose to type 1 (early onset)diabetes. David’s group has beenawarded a grant from the JuvenileDiabetes Research Foundation to studypotential common mechanisms of thesediseases.

Current ResearchFinding more disease genes will requireanalysis of thousands more samples.David’s team have formed a largecollaborative group to enable this, and in February 2008, were awarded a major collaborative grant by theWellcome Trust charity. The group’scurrent collaborators are based in theUK, the Netherlands, Ireland, Finland(genome scan samples), Spain, US,Hungary, Italy, Sweden, Norway(replication samples).

Current aims are to:• Localise precisely from each region

the disease causing genetic change('fine-mapping'). The current markerswe have identified for each region areprobably just tagging (i.e. correlatedwith) the true causal variant.

• Discover more coeliac diseasepredisposing genetic variants

• Understand how the coeliac diseasegenetic variants are influencingbiological function

Bone Marrow FailureProfessor Inderjeet Dokal, with closecolleague Dr Tom Vulliamy, has pursued aresearch interest in the biology of aplasticanaemia and bone marrow failure, a groupof paediatric disorders characterised by theinability to make adequate numbers of redblood cells. The conditions may lead toearly death from infection or bleeding ifadequate treatment is not given.

Scientifically, the studies on this raredisease have made a connection with

aplastic anaemia and the key enzymetelomerase, which maintains the telomericends of all chromosomes. It has beendiscovered that several key components of the enzyme are also mutated in differentgenetic subtypes of anaemia.

These findings have not only shown theimportance of telomerase in humans but have also provided the platform forbetter diagnosis and future treatmentstrategies The immediate and futureresearch aims are to establish the genetic

basis of many uncharacterised cases of aplastic anaemia, determine theirfunctional significance in aplastic anaemia, and explore how these may bemanipulated for future treatment strategies.This work is supported by a Wellcome TrustProgramme Grant which has recently beenrenewed for another five years and many ofthe papers have been published in NatureGenetics.




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Professor of Haematology, Inderjeet Dokal


Professor of Viral Pathology, Aine McKnightsee profile p34


30

Infection, Inflammation and Repair

These inter-related fields of research are particularly strong at Barts and The London withworld-class researchers in all the major Institutes of the School.

In the 2008 Research Assessment Exercise, the Institute ofCell and Molecular Science, returned in Hospital Subjects, wasranked joint 1st in the UK with Cambridge and Edinburgh interms of 3* and 4* outputs and was joint 7th overall out of 28,ahead of Manchester, Newcastle and Southampton.

The William Harvey Research Institute, returned inPreclinical and Human Biological Sciences, was ranked 3rdin terms of 3* and 4* outputs, and 4th overall out of 13,ahead of Kings College London, Bristol and Nottingham.

The School plays an integral role in the UK’s fight against TB through the Health Protection Agency’s MicobacterialReference Unit, led by Professor Francis Drobniewski. The Unit’s work involves collaborations with academic staff in the School’s Centres for Infectious Diseases and PrimaryCare, as well as community health staff throughout eastLondon. Barts and The London School of Medicine andDentistry, and the Trust are recognised as being at theforefront of research and clinical practice in TB.

The MRU detects, identifies and isolates mycobacteria - the organisms which cause TB - and advises on treatment. Its research interests include all aspects of TB and relateddiseases - particularly the interaction of TB and HIV (a growing health concern) - both in the UK andinternationally. It is one of a global network of 23 such units run by the World Health Organisation (WHO).

Focus is on disease diagnosis, the molecular epidemiology of TB and HIV, understanding drug resistance and diseasetropisms, and broader translational research and public healthproblems posed by these diseases both in the UK andoverseas. An international group of staff work on collaborativenational and international clinical, laboratory and public healthtopics relating to TB and HIV in Russia and Ukraine and inpartnership with institutions in Africa.

HIV Research led by Professor Aine McKnight focuses mainlyon the interface between HIV and the immune system withregard to humoral immunity and a novel innate immunemechanism (Lv-2) that inhibits HIV replication after cellularentry resulting in abortive infection. She has mapped the twoviral genes involved in overcoming this antiviral effect and iscurrently mapping the host gene(s) involved.

Other current research interests lie in HIV tropism and co-receptor use. HIV infects mainly T-cells and macrophagesthrough the use of CD4 and co-receptors usually either CCR5 or CXCR4 chemokine receptors. Recently, we have

shown that viral envelopes amplifed directly from plasmaalmost always additionally use a related chemokine receptorCCR3 just as efficiently as CCR5.

Professor Aine McKnight is also among a number of scientiststaking part in a $25.3 million international researchconsortium searching for an HIV vaccine. The grant is one ofthe largest awards in a $287 million, five-year programme of16 grants provided by the Bill and Melinda Gates Foundationto establish an international network of HIV vaccine discoveryconsortia, known as the Collaboration for AIDS VaccineDiscovery.

There is also extremely strong translational HIV researchfunded by the MRC and led by Dr Claudia Estcourt

Immunology and inflammation in the gastrointestinal tractis the subject of Professor Tom MacDonald's research group.His principal research effort is to try to understand the reasonswhy individuals develop Crohn’s disease, a seriousinflammatory disease of the gut. Professor MacDonaldidentified the key role of the cytokine TNFα in Crohn’s disease,which has led to successful new therapies. Principally fundedby the MRC, BBSRC and EU FP7 and with a very strongEuropean collaboration, MacDonald has published extensivelyin top journals on the control of TGFβ signalling in the gut.Ongoing studies are aimed at trying to tolerise gut T cells inCrohn’s disease to reset the immunologic thermostat, whichcontrols immunity in the gut of healthy people. ProfessorMacDonald works alongside other immunologists such as DrDan Pennington (funded by the Wellcome Trust) and Dr AndyStagg, the world leader in the study of dendritic cells in thegut.

Inflammation research investigates the basic mechanismscontrolling various components in inflammation and thepotential to modify these using, for example, gene-therapy,anti-inflammatory peptides, and agonists and antagonists thattarget novel inflammatory pathways. These highly integratedprogrammes of research use a range of techniques frommolecular biology and genetic engineering of cells andmolecules, to in vivo models of inflammation, where we have agreat strength. A strategic investment of £1.45 million hasbeen made to create a new Centre of Experimental Medicineand Rheumatology with a strong research programme in jointand tissue repair and stem cell therapy, headed by ProfessorCostantino Pitzalis. The strong translational element of thisgrouping funded by Wellcome, ARC and MRC is tightly linkedinto the Barts and The London NHS Trust clinicalrheumatology service.



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Sussan Nourshargh PhD FBPharmacolS Professor of MicrovascularPharmacologyCentre for Microvascular Research

Professor Sussan Nourshargh wasappointed Professor of MicrovascularPharmacology at the William HarveyResearch Institute in 2007 to establishand head a new Centre focussing onMicrovascular Research. ProfessorNourshargh heads an internationallyrespected research group investigatingmechanisms of leukocyte trafficking andregularly contributes to key national andinternational conferences. She wasawarded the Quintiles Prize foroutstanding contribution toImmunopharmacology from the BritishPharmacology Society in 2001 and

became Fellow of the BritishPharmacological Society in 2005.Sussan has acted as a committeemember on the British HeartFoundation Project Grant panel (2002-2006), was a co-founder and committeemember of the London Vascular BiologyForum (2001-2008) and is currently theTreasurer of the UK Adhesion Societyand Programme & FellowshipCommittee member for the AmericanSociety of Investigative Pathology (ASIP).

Sussan Nourshargh graduated inPharmacology from University CollegeLondon in 1982 and obtained her PhDin Pharmacology from King’s CollegeLondon in 1986. As her PhD projectaddressed mechanisms of neutrophilactivation in vitro, she extended herinterests in this area to the in vivoinflammatory scenario through post-doctoral work at the MRC ClinicalResearch Centre based in Harrow andthen at the National Heart & LungInstitute (NHLI) in London where shewas appointed to Lecturer position in1988. Her continued productiveresearch in the field of leukocytemigration resulted in the award of aWellcome Trust Career Fellowship(1990) followed by a Wellcome TrustUniversity Award (1996) with the latterleading to a tenured academic position

within NHLI at Imperial College Londonin 2001. During these periods she rosethrough the academic ranks andbecame Professor ofImmunopharmacology at ImperialCollege London in 2006, the same yearas she was awarded a Wellcome TrustProgramme Grant to extend her workinto mechanisms of leukocytetransmigration in vivo.

Current research interestsThe group’s research focuses on themechanisms of leukocyte trafficking into sites of inflammation and theconsequence of this response onregulating the phenotype of emigratedcells (Ley et al., Nature ReviewsImmunology., 2007; Nourshargh &Marelli-Berg, Trends in Immunology.,2005). Their principal experimentalapproach is the use of advancedimaging techniques (eg intravital and confocal microscopy)for analysis of leukocyte/vessel wallinteraction in vivo. The team’s work issupported by The Wellcome Trust, TheBritish Heart Foundation and fundsfrom the EU and has been published inhigh ranking journals such as Journal ofImmunology, Blood, Journal ofExperimental Medicine, Nature Reviewsand Science.

Suzanna McDonald PhD studentCentre for Infectious Diseases

“The Barts and The London SMD campuses combine some of the oldest history inLondon at the Bart's site in West Smithfield, whilst here at the Institute of Cell andMolecular Science in Whitechapel we have one of the funkiest buildings in science!The open-plan structure of the building creates interactions with multipledepartments. The facilities and equipment within the school as a whole are world-class, such as the Genome Centre, and our extensive array of imaging equipment.”


Infection, Inflammation and Repair (cont)


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Some leading Barts and The London Researchers on Infection,Inflammation and Repair

Professor Amrita Ahluwalia's work focuses on mechanisms ofvascular homeostasis in inflammation and particularly the role of the endothelium. Recent research areas include studiesinvestigating the role of endothelium-derived hyperpolarisingfactor (EDHF) in cardiovascular protection and the influence of sex on its activity, investigating the role of C-type natriureticpeptide as an EDHF, dissection of the mechanisms involved invascular inducible nitric oxide synthase expression in sepsis,Investigation of the role of TRPV1 in vascular reactivity andmechanisms involved in nitrate and nitrite-induced bioactivity.Professor Ahluwalia’s work on the ability of beetroot juice to lowerblood pressure attracted international attention.

Dr Francesco Dell'Accio's research focus is cartilage biology andthe biological repair/regeneration of adult articular cartilage. Thefindings that progenitor cells persist within adult synovial jointsand in adult articular cartilage (Dell'Accio et al. Experimental CellResearch. 2003) and that the injured adult human articularcartilage deploys an early signalling response includingmodulation of the WNT and BMP signalling pathways (Dell'Accioet al. Arthritis Research and Therapy 2006) suggests that repairmechanisms persist in the adult joints. His current research istherefore focussed on the unravelling of the molecular signallingtriggered by injury to the articular cartilage and playing a role inthe repair mechanisms.

Professor Bart Vanhaesebroeck is a world expert on the biology of PI3Kinases. The main interests of his group include signaltransduction in cell migration, proliferation, survival, intracellularvesicular transport, in the context of cancer, inflammation andimmunology, angiogenesis, metabolism and stem cell biology.Collaborative efforts with industry are under way in the preclinicaldevelopment of isoform-selective small molecule inhibitors forPI3K to translate this preclinical work to early phase clinical trials.

Dr Toby Lawrence trained with Michael Karin in San Diego, wherehe used molecular genetics to study the role of cell signallingpathways in the regulation of inflammation and immunity. Thesestudies focussed on the role of IkappaB kinase (IKK) in thebiology of inflammation, using tissue specific gene targeting toestablish the specific role of IKK in the inflammatory response.The major research focus of the group is to understand thefundamental mechanisms by which inflammation promotescancer, with particular reference to the role of stromal andinflammatory cells in carcinogenesis.

The Biochemical Pharmacology group under Professor Rod FlowerFRS and Professor Mauro Perretti, investigates the mechanism ofaction of anti-inflammatory drugs including Cox inhibitors (NatureReviews Drug Discovery 2004) and especially the glucocorticoidsteroids (PNAS 2002; Journal of Immunology 2003; Blood 2005).Much of the research investigates the pharmacology and thebiology of Annexin A1, a protein that is induced by glucocorticoidsand has profound immunomodulating properties. Funded by theWellcome Trust (programme and projects; >£1.6 million) and theBritish Heart Foundation (£225,000 project), this line of researchspans all aspects of Annexin A1 biology ranging from cell biologythrough to its role in human disease (Nature Medicine 2002; TheFASEB Journal 2006, 2008; Blood 2006, 2007 and 2008; JBC2007; Nature Reviews Immunology in press). Other majorresearch areas evolve around galectins (fellowships of the ArthritisResearch Campaign [ARC] UK; £600,000) and melanocortinpeptides (£230,000, arc UK). Industrial funding derives fromUnigene Corp (NJ; $1.2 million, with licencing of 2 patents),Action Pharma (£250,000 melanocortin research) and UCB(£180,000), with other drug discovery work funded by HeptagonFund.

A recent recruit is Professor Sussan Nourshargh who leads theCentre for Microvascular Research, funded by a programme grant from the Wellcome Trust and the British Heart Foundation.Professor Nourshargh’s work on imaging of inflammatory cellsleaving tissues is world-leading and her discovery of endothelialjunction proteins being expressed in the brain (published inScience) has opened up exciting new avenues of investigation.

The Bone and Joint Unit is a leading centre for inflammationresearch, which, under Professor Yuti Chernajovsky, works on the development of gene transfer strategies for the treatment ofrheumatoid arthritis and other autoimmune diseases via cellularengineering, molecular design and genetic engineering. The group has extensive funding from the ARC and MRC. One recent development has been the design of latent cytokines by recombinant DNA technology. The designed fusion proteinbetween the latency associated peptide (LAP) of TGFβ and acytokine with therapeutic potential are linked via ametalloproteinase (MMP) cleavage site which renders the cytokineinactive until it reaches a site of inflammation. The LAP providesa shell that inhibits the interaction of the cytokine with itsreceptors increasing its half life and ensures delivery to sites ofdisease.




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Costantino Pitzalis, MD PhD FRCPProfessor of Experimental RheumatologyCentre for Experimental Medicine andRheumatology

Professor Costantino Pitzalis wasrecruited to the William Harvey ResearchInstitute at Barts and The London Schoolof Medicine and Dentistry in 2007 todirect the Centre for ExperimentalMedicine and Rheumatology. Followingearly clinical training in Italy he came toEngland in 1985 as a Research Fellow to the Department of Rheumatology atGuy’s Hospital. Here he carried out fulltime laboratory research for 4 years thatlead to a PhD at the University ofLondon. He then went back to full timeclinical training in General Medicine inthe UK, gaining the MRCP in 1992. He returned to the Department ofRheumatology at Guy’s in 1993 as theArthritis Research CampaignLecturer/Senior Registrar. In 1996, hewas awarded a Senior Lectureship/CareerDevelopment Award from the WellcomeTrust and in 2000 was appointed to theChair of Experimental Rheumatology atKing’s College London School ofMedicine.

Professor Pitzalis has published over 100full papers, a large number in journalswith an impact factor of 5 or above. Hehas been awarded over £4.5 million inpeer reviewed grants in the last threeyears including funding from the MRC,

Wellcome Trust, Arthritis ResearchCampaign, Nuffield Foundation,European Union (FP6) as well as other smaller medical charities.His clinical interests are mainly inimmune/inflammatory rheumaticdiseases including rheumatoid andpsoriatic arthritis. His major researchinterests focus in the field of adhesionbiology and in the pathogeneticmechanisms of damage and repair ofjoint tissues.

Current research interestsProfessor Pitzalis’ principal interestsrevolve around the role of adhesionphenomena in the pathogenesis ofimmune mediated inflammation and how these processes can be modulatedtherapeutically both by conventionaldrugs e.g. glucocorticoids and newbiologic agents. In addition, he hasdeveloped a novel platform technology:“the human/SCID mouse transplantationmodel” that has been successfully usedfor dissecting molecular mechanisms ofinflammation and for targeting humansynovial microvascular endothelium by in vivo phage display selection. Morerecently, with the recruitment of DrFrancesco Dell’Accio, the Centre hasextended its interests in the field ofcartilage biology with particular referenceto the mechanisms of tissue damage andrepair. Main research areas can besummarised as follows:

• Tissue specific homing in thepathogenesis of chronic inflammation

• Chemokines in cell migration and neo-lymphoneogenesis

• Identification of novel of tissue specifictargets using phage display technologyto target human tissues transplantedonto SCID mice.

• Functional studies of targeting cellularand molecular pathways ofinflammation in the human/SCIDmouse transplantation model.

• Regulation of inflammation byglucocorticosteroids and new biologic agents

• Mechanisms of joint tissue damageand repair.

The Medical Research Council invested £681,000 in developing a Pathobiology ofEarly Arthritis Cohort (PEAC). The goal ofPEAC is to create a unique resource withhigh-density data including genomic andtranscriptomic analysis coupled withdetailed imaging and clinical phenotypingto enable scientists to examine thecellular and molecular mechanismsdetermining diverse disease severity andresponse to treatment in rheumatoidarthritis (RA).

RA is one of the most important chronicinflammatory disorders in the UK. Itaffects approximately 1 per cent ofadults, causes considerable morbidity,reduces quality of life and increasesmortality and results in large medicalcosts (over £1.2 billion/year).

This cohort will be of major interest toacademia, industry and governmentbodies as it will represent an idealplatform for innovative clinical trials thatwill incorporate imaging and biologicalparameters to determine early efficacy on structural damage progression withsignificant clinical, research and health-economic benefits.

Professor Pitzalis will lead a Consortiumof 5 Centres of excellence including theMRC Centre for Immune Regulation inBirmingham (Prof C Buckley); the Centrefor Rheumatic Diseases in Glasgow (ProfIB McInnes); the Kennedy Institute forRheumatology Imperial College - London(Prof PC Taylor) and the AcademicDepartment of Rheumatology – King’sCollege London (Dr E Choy) to developPEAC.




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Aine McKnight MiBiol MSc PhD Professor of Viral Pathology

Throughout her academic career,Professor McKnight has been interestedin HIV/AIDS. In 1987, she joined theteam of Robin Weiss at the Institute ofCancer Research, London, to study therole of neutralising antibodies to HIV-1and HIV-2 in pathogenesis. She wasawarded an MSc in Immunology in1990 by King's College, London, and a PhD by University of London(supervised by Paul Clapham) in 1996.

In 2000, she won a fellowship (RCDF)from The Wellcome Trust to develop anindependent research group to focus onnon-coreceptor determinants of HIVreplication in cells at The Wohl VirionCentre, University College London. Sheis currently a Medical Research Council(MRC) Senior Non-clinical Fellow(awarded in 2005).

The interests of Professor McKnight’sgroup focus mainly on the interfacebetween HIV and the immune systemwith regard to humoral immunity and anovel innate immune mechanism (Lv-2)that inhibits HIV replication after cellularentry resulting in abortive infection. Thegroup mapped two viral genes involvedin overcoming this antiviral effect and iscurrently mapping the host gene(s)involved.

With regard to humoral immunity toHIV-1 infection the group mainlyfocuses on the role of neutralisingantibodies in controlling HIV-1 and 2

replication. They have shown thatactivation of the classical complementpathway by serum antibodies can beimplicated in the control of primary HIV-1 viremia. More recently they haveshown that in acute infection, virusesdevelop with envelopes that are highlysensitive to serum antibody mediatedneutralisation but eventually theseviruses are replaced in the blood byones that escape serum neutralisingantibodies.

The group also has strong interests inHIV tropism and co-receptor use. HIVinfects mainly T-cells and macrophagesthrough the use of CD4 and co-receptors usually either CCR5 or CXCR4chemokine receptors. Recently theyhave shown that viral envelopesamplifed directly from the plasmaalmost always additionally use a relatedchemokine receptor CCR3 just asefficiently as CCR5.


Basic and Translational Neuroscience

Neuroscience research activity at Barts and The London lies predominantly within the Institute of Cell and MolecularScience but is an important strength across the School.Research in neuroscience is focused on translational work in the fields of traumatic injury, degenerative disorders andneuro-oncology, building on both internal investment andexternal funding.

The Institute of Cell and Molecular Science, returned in Hospital Subjects, wasranked in the 2008 Research Assessment Exercise joint 1st with Cambridgeand Edinburgh in terms of 3* and 4* outputs and was joint 7th overall out of 28, ahead of Manchester, Newcastle and Southampton.

A major objective is to strengthen the links between academic and clinicalactivity in Neuroscience and, to this end, the establishment of a NeurologyClinical Outcomes Unit is planned, along with the formation of an acute spinalinjury unit with close links to the Helicopter Emergency Medical Service andtrauma work within Barts and The London NHS Trust. To deliver this agenda, the group has appointed a new head, Professor Gavin Giovannoni, a world-leaderin neuroimmunology.

Neuroscience research focuses on three interrelated topics:

• The role of primary sensory neurons and effects of peripheral nerve injury

• Traumatic and degenerative disorders of the central nervous system

• Molecular mechanisms of development and central nervous systemtumorigenesis - a new theme and one which reflects the importance of cancer both for the School and for Barts and The London NHS Trust

Primary sensory neurons. Work here focuses on the fundamental role played byneurotrophic factors and cytokines in regulating adult dorsal root ganglion (DRG)cells, the importance of such factors in pain states, and strategies to promoteperipheral nerve regeneration. Professor John Priestley’s group was the first toestablish that nociceptive DRG neurons comprise two main subpopulationswhich differ in their growth factor dependence and expression of neuropeptides.This work is continuing, with further study of the properties of nociceptive DRGneurons, their expression of key transduction molecules and ion channels, andtheir response to injury.

Professor Priestley’s group has shown that novel silks developed by OxfordBiomaterials can support neural regeneration. This work is now funded by a £250,000 grant from Kinetique, awarded to establish a start-up company(Neurotex) and develop silk-based conduits for peripheral nerve repair.

The Centre’s pre-clinical studies are complemented by clinical studies onorofacial neuropathic pain, on perioperative pain relief and on arthritis.


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Traumatic and degenerative central nervoussystem injury. The Centre has an establishedreputation for work on degenerative disordersincluding motoneurone disease and traumaticinjury to the spinal cord. This has recently beenfurther strengthened with the establishment of a neuroimmunology group with a focus onmultiple sclerosis (MS) and basal gangliaautoimmune diseases.

Research ranges from cell and molecularstudies in vitro, through in vivo rodent models,to clinical trials. This translational focus isfacilitated by the presence of a full-time trialscoordinator. Ongoing studies include rootavulsion injury, molecular strategies to promoteregeneration and hence link closely with theperipheral nerve work reviewed above. Studieson spinal cord injury include the use offibronectin implants to fill cystic cavities andsupport axonal regeneration, strategies topromote regeneration after ventral root avulsioninjury, and use of omega-3 polyunsaturated fattyacids (PUFAs) as neuroprotective agents. Aphase 1 safety study of PUFA treatment inspinal cord injury is underway , as is a pilotclinical study in Alzheimer’s disease.

Key recent achievements related to motorneuron disease include the linkage of axonaltransport defects to motor neuron loss in dyneinmutations and gene array analysis of commonmechanisms underlying motor neuron diseaseand cell death following spinal cord injury. The neuroimmunology group leads the field in studies of endocannabinoids in MS and thepossible therapeutic use of cannabinoids in MS.They have also highlighted the role of anti basalganglia autoantibodies in movement disorders,and are developing novel treatments for MSbased on induction of immune tolerance.


36

Professor of Neuroimmunology, David Baker


37

Daniel ChewPhD studentNeuroscience Centre

“Like everyone who visits here, I was thoroughly impressedwith the labs in the Blizard Building at Whitechapel, and thiswas my main reason for choosing to study a PhD at Barts andThe London School of Medicine and Dentistry. With state-of-the-art equipment, and open, integrated lab space, it providesan excellent place to undertake research.'

Professor of Neurology, Gavin Giovannoni


Development and neuro-oncology: The molecular events thatdetermine gene transcription and cellular differentiation are beingstudied, both in normal development and in tumour formation.Major themes currently under investigation include: the role ofchromatin and nuclear architecture in transcription (Sheer);genetic defects associated with glioblastoma multiforme (Sheer);the molecular events that control cerebellar granule celldevelopment and their contribution to the pathogenesis ofmedulloblastoma (Marino); and the role of neural stem cells and self renewal mechanisms in the ontogenesis of brain tumours(Marino). The latter studies provide a strong link with stem cellwork in other research centres at Barts and The London.

38

Some leading Barts and The London Neuroscience Researchers

Professor Gavin Giovannoni’s research interests include:multiple sclerosis; immune-mediated movement disorders, and immune tolerance strategies. He is setting up a clinicaloutcomes unit which will build important bridges betweenneurology, neurosurgery and neurohabilitation.

Professor Silvia Marino’s main research interest lies inprogenitor cells and tumourigenesis, its role in braindevelopment and how that gives rise to brain tumours. Sheworks with mouse models using a translational approach toassess relevance in humans.

Professor David Baker leads the field in the study of howcannabinoids effect symptom control in MS. The bodyproduces its own cannabis-like molecules to control hownerves work. Professor Baker’s work involves manipulating thenatural immune system so it can bind to the natural dockingmolecules and relax the nerves.

Professor Denise Sheer’s research aims to understand thebiology of the human genome and the contribution of geneticchanges to cancer. A major focus of her work is on braintumours, primarily in children, where she aims to understandthe pathways that give rise to cancer, derive a molecularclassification, predict responses to treatment and to identifytargets for new forms of therapy.


Basic and Translational Neuroscience (cont)

Professor Denise Sheer



39

Dentistry

Barts and The London is an international leader in oral and dental sciences and, in the 2008 Research Assessment Exercise, was ranked 1st in the UK for 4* and3* outputs and 2nd in the UK overall, according to the Times Higher Education.Combining a strong tradition of clinical, epidemiological and public health researchand a solid research base, Barts and The London is at the forefront of theadvancement of dental care. Cutting-edge laboratories and first class facilitiesenable the work of these research teams and clinical trials to be carried out to the highest ethical and governance standards.

Significant local research in dentistry includes internationally renowned work on the molecular biology of the periodontal pathogen, Porphyromonas gingivalis. This has attracted significant funding and currentinvestigations include the development of novel antimicrobial achievements based on the understanding of microbial virulence factors in bacteria.

Work on the aetiology and treatment of periodontal disease includes longstanding studies on the biology andapplication of growth factors of periodontal regeneration and wound-healing. In addition, work continues tounderstand host-bacterial interactions and the regulation of mechanisms of tissue damage, including boneresorption, during periodontitis. Large multi-disciplinary studies are taking place to identify and investigate the role of a range of risk and prognostic factors in aggressive periodontitis. A large tissue bank and databaseallows a complex modelling of the relative role of different risk and aetiological factors, including psychosocialand behavioural factors, clinical factors, microbiological and genetic factors and a range of proteomic markers.

Clinical and non-clinical academics with expertise in conservative and paediatric dentistry, anatomy,biophysics, chemistry, crystallography, electronic engineering, epidemiology and materials science all worktogether to develop x-ray microtomography and other x-ray microscopes for new ways to look at the biology of teeth and bones in the mouth.

Barts and The London is also at the forefront of research in oral cancers. Head and neck carcinoma, the sixthmost common cancer worldwide, is a significant public health issue in the local population of east London.Public health and clinical research programmes are utilised to advance understanding in this area, and thereis a particularly strong link in oral cancer with women at the East London Mosque. Longstanding research andimplementation programs in tobacco cessation, including those addressed specifically at the unique publichealth issues in the local area, are a key part of the research agenda. The research provides a demonstrablepractical impact on health service delivery whilst addressing the most important area of risk factormanagement in both primary care and specialist dental practice.


Professor of Medicine in Relation to Oral Health,Farida Fortune


41

Some leading Barts and The London Dental Researchers

Mike Curtis is Professor of Microbiologyand Director of the Institute of Cell andMolecular Science at Barts and theLondon. He is an international expert inoral microbiology in particular the microbialpathogenesis of periodontal disease. Hisresearch, funded principally by the MRCand the NIH, has made fundamental

advances in our understanding of the virulence mechanisms of periodontal bacteria. He was awarded the InternationalAssociation for Dental Research Distinguished Scientist Award in 2005, was made an Honorary Fellow by the Faculty of DentalSurgery of the Royal College of Surgeons in 2008, and iscurrently the President of the British Society for Dental Research.

Ken Parkinson is Professor of Head and Neck Cancer. Hisresearch, funded through the European Union and BBSRC, isfocussed on the mechanisms of oral keratinocyte immortalisationand the influence of telomere dysfunction in oral cancer. Hiswork has lead to the hypothesis that oral squamous cellcarcinomas may progress by two distinct routes only one ofwhich leads to cellular immortalisation. Professor Parkinson won the Golden Award at the European Head and Neck Cancermeeting in 2003.

Farida Fortune is Professor of Medicine in Relation to Oral Health and Director of the Institute of Dentistry. In additionto an active role in oral cancer research she focuses on theaetiopathogenesis of Behcet’s disease, oral Crohn’s disease and oral-submucous fibrosis and related systemic diseases ofimmune dysfunction in the mouth. She has established one ofthe largest patient bases of these conditions which has facilitatedthe analysis of the immunogenetics of these multisystemdiseases to identify the role of genetic polymorphisms in their aetiology and immunopathogenesis.

Gareth Thomas is Professor of Oral Pathology. His researchfocuses on the regulation of cancer cell invasion by invasion-promoting proteins expressed by malignant cells and themechanisms through which the tumour stroma influences

invasion. In collaboration with colleagues in the CRUK fundedTumour Biology Group at the Institute of Cancer, he hasidentified the integrin αvβ6 as a target for tumour imaging andtherapy and demonstrated a novel link between this ligand andcyclo-oxygenease enzymes: αvβ6 dependent invasion can besuppressed by inhibition of COX-2. In 2004 he was awarded afive year Clinician Scientist Fellowship from the HealthFoundation to develop novel tumour therapies based on αvβ6 expression in head and neck cancer.

Francis Hughes is Professor of Periodontology. His researchinterests include the role and mechanisms of risk factors inperiodontal disease; the biology of osteoblast function andperiodontal ligament cell lineage; the biology and clinicalapplication of methods of bone and periodontal regeneration. His work on risk factors includes clinical studies of risk andprognosis and the mechanisms of the interaction of bacterialfactors with host responses including cytokine production andbone resorption. These studies are facilitated by the assembly of a large well characterised cohort of subjects with aggressiveperiodontal disease established through MRC funding. He iscurrently President of the Pan European Federation ofInternational Association for Dental Research.

Dr Virginia Kingsmill, Clinical Senior Lecturer, was awarded aDepartment of Health Clinician Scientist Fellowship award tocompare the structure, mineralisation and remodelling of themandible with that of other bones with the long term aim ofunderstanding the processes and mechanisms of alveolar boneremodelling indentate and edentulous jaws and the response tosystemic regulatory factors.

Dr Muy-Teck Teh is a Lecturer in head and neck cancer. Hisresearch interests are focused on finding new biomarker genes for predicting early oral cancer formation. Currently studies arebased around a known cancer gene called FOXM1B usinghuman oral keratinocytes cells as the research model. Earlyresults have showed that FOXM1B may be an early cancermarker which is expressed at higher level in pre-cancer andcancer cells compared to normal cells. The future aim is todevelop a diagnostic test using the Gene Chip technology thatcan guide treatment strategy.


Dentistry (cont)


42

Oluyori AdegunPhD studentCentre for Clinical and Diagnostic Oral sciences

“Prior to my PhD I undertook an MSc in Experimental Oral Pathology at Bart’s and The London School of Medicine and Dentistry. The driving force behind this choice was the School’s world renowned reputation for excellence in both teaching and research, particularly in the field of Dentistry. My experience was a very positive one; the teachingsessions were enlightening and the laboratory sessions in the new, state-of-the-art Blizard building were stimulating andinspiring. These experiences fuelled my interest and sparked my desire to continue in this field. Hence, it was a naturaldecision to continue at Barts and The London.

“Bart’s and The London offers a fantastic opportunity to work in a multidisciplinary team, enabling development of avast array of key proficiencies such as clinical, leadership, teaching, research and analytical skills, increasingly requiredin modern day Medicine and Dentistry. It also provides the opportunity to learn cutting edge/revolutionary techniquesand the chance to work and collaborate with distinguished professionals, experts in their respective specialties.”

Lecturer in Head and Neck Cancer, Dr Muy-Teck Teh


Senior Lecturer in Preventative Cardiovascular Medicine and Consultant Cardiologist, Dr David Waldsee profile p46


Preventive Medicine and Public Health

Barts and The London is a world-leader in discovering and understanding thecauses of disease so that these can be prevented.

The key element is the study of whole populations to determine the incidence of disease in different groups: in men, in women, in younger people compared with older people, in people in different countries,occupations, or genetic background. All of this provides clues to the causation of disease: for example, therelatively recent discovery that the common neural tube birth defect, spina bifida, is caused by a vitamindeficiency that is present in many populations, including those in economically developed countries.

Preventive medicine and public health are located in two Institutes within the School: the Wolfson Institute of Preventive Medicine; and the Centre for Health Sciences in the Institute of Health Sciences Education.

The Wolfson Institute of Preventive Medicine, returned in the 2008 Research Assessment Exercise inEpidemiology and Public Health, was 2nd out of 21 in terms of 3* and 4* outputs, and 3rd overall, ahead of Oxford, University College London and Bristol. In Health Services Research, Barts and The London wasranked 4th overall out of 28, ahead of Oxford, University College London and Kings College London.

The Wolfson Institute of Preventive MedicineWith an international reputation, the Wolfson Institute is a leading world centre for research and teaching inepidemiology, preventive medicine, and public health. The main areas of research are cardiovascular diseaseprevention, cancer prevention, cancer screening, antenatal screening and perinatal epidemiology, smokingcessation, mental health and medical statistics.

The Wolfson Institute is distinctive in that it captures scientific opportunities that arise from laboratory-basedepidemiological and screening research into common diseases such as cardiovascular disease, cancer andcongenital malformations through integrating epidemiology and statistics with pathology and clinical medicine.Much of the research is funded by medical charities including Cancer Research UK, Wellcome Trust, and theBUPA Foundation.

The Institute comprises three centres:

• Centre for Environmental and Preventative Medicine headed by Professor Sir Nicholas Wald

• Cancer Research UK (CRUK) Epidemiology, Mathematics, and Statistics (EMS) Unit, headed by Professor Jack Cuzick

• Centre for Psychiatry, headed by Professor Stephen Stansfeld

Professor Peter Hajek heads the Academic Psychology section, part of the Centre for Environmental andPreventative Medicine which is based at Whitechapel and includes the Tobacco Dependence Research Unit.

There is an active group of statisticians and a statistical advisory service headed by Professor Joan Morris.

Over 150 staff work in the Institute, which houses state-of-the-art laboratories and screening suites. There is a focus on academic discipline, the translation of research into public health strategies and their practicalimplementation - all dedicated to the reduction of disease and disability.

Research is conducted using a number of methods, such as large scale randomised prevention trials,screening research projects and epidemiological studies into the causation of disease. Teaching and researchgo hand in hand; there are study days and lectures in areas such as Down’s syndrome, Medical Psychologyand postgraduate courses in Transcultural Mental Healthcare.

Many discoveries and applications from the Wolfson Institute have been adopted by health agencies worldwidewith staff playing a key role in translating research findings into practice.

44



45

Examples of recent ground-breaking research include the development ofPolypill, the drug treatment preventing myocardial infarction and stroke, forpeople aged 55 and over and to be taken as a single daily pill. Ranked as one of the top medical stories of 2003, this pill may reduce the incidence of heartdisease and stroke by over 80 per cent.

Barts and The London is also at the forefront of antenatal screening research.This has resulted in two major studies, the SURUSS study and the FASTERstudy, the largest worldwide project on the subject of antenatal screening,published in 2006. This study yielded results on the screening performance of different combinations of first and second trimester markers in antenatalscreening for Down’s syndrome. It showed that the Integrated Test (combiningfirst and second trimester screening), developed by the centre previously, has by far the best screening performance, detecting 85 per cent of affectedpregnancies with a false positive rate of only one per cent. The National DownSyndrome Cytogenetic Register, maintained by the centre, is also a valuableresource, providing information on numbers of prenatal diagnoses and live birthsand the exact nature of the association between Down’s syndrome risk andmaternal age.

Prominent in the work of cancer research have been trials of tamoxifen and more recently the aromatase inhibitor anastrozole, in the treatment of womenwith established breast cancer and as a primary prevention of breast cancer. A significant reduction in the incidence of breast cancer was discovered withtamoxifen, while the ongoing international trial is expected to show an evengreater preventive effect from anastrozole in postmenopausal women atincreased risk (see Cancer p14).

Centre for Health SciencesThe Centre for Health Sciences led by Professor Chris Griffiths is makingremarkable strides in implementing a translational research strategy. Work to date has centred on the role of vitamin D in health and illness. Staff haveestablished the Translational Research Unit for the MRC Asthma UK Centre inAllergic Mechanisms of Asthma (www.asthma-allergy.ac.uk.) Other collaborationsinclude the Wellcome Centre for Clinical Tropical Medicine(http://www1.ic.ac.uk/medicine/about/institutes/tropical/), and with the University of California, Riverside (http://www.biochemistry.ucr.edu/faculty/norman.html).

With a grant from the Newham Development Agency, Professor Griffithsestablished a randomised trial and cross sectional analysis examining thehypothesis that vitamin D favourably modified the immune response againsttuberculosis. This work was the first randomised assessment of the therapeuticcapacity of vitamin D, despite its use prior to the introduction of antibiotics. It also led to a series of important publications supporting the hypothesis,elaborating the mechanisms of action, and for the first time highlighting the role of neutrophils in the anti-mycobacterial immune response. [Martineau AR,American Journal of Respiratory and Critical Care Medicine 2007], [MartineauAR, Journal of Clinical Investigation 2007], [Martineau AR, Journal ofImmunology 2007], [Martineau AR, The Journal of Steroid Biochemistry andMolecular Biology 2007]

Some leading Barts and The London PreventiveMedicine and Public Health researchers:

Professor Sir Nicholas Wald FRS, Director,Wolfson Institute of Preventive Medicine,pioneered the field of antenatal screening forcongenital malformation and made discoveriesthat form the basis of screening for neural tubedefects and Down’s syndrome in earlypregnancy. Recent research activities includescreening and treatment for Heliocobacter pyloriinfection and subsequent stomach cancer, andscreening and treatment of hypothyroidism inpregnancy. He is the innovator of the ‘Polypill’, a radical approach to the prevention ofcardiovascular disease, for which trials are being developed.

Dr Anne Szarewski, Wolfson Institute ofPreventive Medicine, leads research to studydifferent markers for cervical screening, andalso two HPV vaccine trials. Her team hasdeveloped two preventative vaccines that haveshown great promise in clinical trials: onecontaining HPV types 16 and 18; the othercontaining types 6 and 11 in addition to 16 and 18.


Preventive Medicine and Public Health (cont)

Professor Sir Nicholas Wald, FRS


46

Dr David Wald MA MBBS MRCP MDSenior Lecturer and ConsultantCardiologist

Dr David Wald is an InterventionalCardiologist with an interest in theprevention of cardiovascular disease.His clinical-academic aims are to bridge the interventional and preventiveapproaches to cardiovascular diseasewhich are often viewed as distinct. He is co-ordinating a proposed randomisedtrial to assess the value of coronaryangioplasty in preventing futurecoronary heart disease events amongpatients receiving angioplasty to treat an acute myocardial infarction.

Dr Wald conducted a randomised trialwhich showed the minimum fullyeffective dose of folic acid for serumhomocysteine reduction, for which hewas awarded the BMA BrackenburyResearch Prize. He has been adviser tothe Food safety Authority of Ireland inhelping them reach a decision ondietary fortication with folic acid.Together with Professors Malcolm Lawand Joan Morris of the Wolfson Instituteof Preventive Medicine at Barts and The London School of Medicine andDentistry he quantified the relationshipsbetween homocysteine, coronary heartdisease, stroke and thromboembolicdisease using meta-analyses ofobservational and geneticepidemiological studies. This wasimportant because it specified theexpected effect of folic acid intake on cardiovascular disease preventionwhich, in turn, showed how even thelargest randomised trials of folic acidsupplementation were underpowered to show the expected effect.

Together with the Director of theWolfson Institute, Professor Sir NicholasWald, and Jonathan Bestwick also at theWolfson, David showed that screeningfor familial hypercholesterolaemia, byserum cholesterol measurement, iseffective if done in early childhood after the first year of life. The findingunderpins a novel “child-parent”population screening strategy thatscreens children and their parentswithin the same programme. He isassessing imaging techniques likecarotid ultrasound and CT scanning inscreening for coronary heart disease todetermine their value in medicalpractice.

David Wald coordinates the PolypillPrevention Programme, a novel servicethat adopts the Polypill approach incoronary heart disease and strokeprevention. With Professor NicholasWald and Professor Malcolm Law hecollaborates in the development andproposed trials of the Polypill itself.


Preventive Medicine and Public Health (cont)

Professor Jack Cuzick, PhDWolfson Institute of Preventive Medicine

Professor Cuzick has pioneered the fieldof chemoprevention of breast cancer. The IBIS I and IBIS II trials have beeninvestigating first tamoxifen and thenanastrozole for prophylactic treatment of breast cancer. He has more recentlylead the introduction of aromataseinhibitors, both for the treatment ofbreast cancer where they represent amajor advantage over tamoxifen, and as a better agent for chemoprevention.Professor Peter Sasieni, anacknowledged expert in survivalanalysis, has extended his work insteering the cervical screening

programme in the UK to playing aleading role in clinical trials of HPVtesting both in the UK and Peru. He is the Director of the Clinical TrialsPrevention Unit, recently established as the only unit specialising in cancerscreening prevention.




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This guide has been produced by the Publications and Web Office for the School of Medicine and Dentistry – Pub3652

For further information contact:Communications OfficeQueen Mary, University of LondonMile End RoadLondon E1 4NSTel: +44 (0)20 7882 3004Fax: +44 (0)20 7882 3703email: [email protected]


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