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University College London

UOA 4 - Other Hospital Based Clinical Subjects

RA5a: Research environment and esteem

University College London UoA4 - RA5a

 

INTRODUCTION

 

UCL’s UoA4 submission embraces 306 Category A staff in the Faculties of Biomedical Sciences and Life Sciences. This represents a world-leading grouping of basic and clinical hospital-based research, underpinned by other UCL Faculties, including Engineering and the Physical Sciences. Strong links with multiple, world-renowned NHS Trusts have recently been further consolidated by three Biomedical Research Centre (BRC) Partnerships (one comprehensive and two specialist). TABLE 1 lists the component Divisions and Institutes of the Faculty of Biomedical Sciences central to this return, their companion Trusts and the BRCs.

 

TABLE 1

Institutes and Divisions of the Faculty of Biomedical Science returned under UoA4:

IO         Institute of Ophthalmology

EI         Ear Institute

EM       Experimental Medicine comprising:

                         Division of Medicine

Division of Surgery and Interventional Sciences (incorporating Institute of Orthopaedics and Musculoskeletal Science)

IWH      Institute for Women’s Health

ICH       Institute of Child Health 

 

Companion NHS Trusts

MEH     Moorfields Eye Hospital NHS Foundation Trust

RNTH    Royal National Throat, Nose and Ear Hospital

UCLH    University College London Hospitals NHS Foundation Trust

RFH      Royal Free Hospital NHS Trust

RNOH   Royal National Orthopaedic Hospital NHS Trust

GOSH   Great Ormond Street Hospital for Children NHS Trust

WH       Whittington Hospital NHS Trust

 

Biomedical Research Centres (BRC)

Comprehensive BRC, UCL/UCLH

Specialist BRC in Child Health, ICH/GOSH

Specialist BRC in Ophthalmology, IO/MEH

 

UoA4 comprises six of the 13 research Institutes/Divisions of the UCL Faculty of Biomedical Sciences (FBS).  Other components of the FBS are being returned to UoA2, Cancer Studies; UoA3, Infection and Immunity; UoA6, Epidemiology and Public Health; UoA9, Psychiatry, Neuroscience and Clinical Psychology; UoA10, Dentistry; and UoA11, Nursing and Midwifery. The FBS co-ordinates its components, and interacts closely with the Faculty of Life Sciences (FLS) and other Faculties of UCL. Indeed it is the increasing integration across UCL, and with partner NHS Trusts, which enables a translational research agenda and lies at the heart of UCL’s recent successes and its strategy for future growth and accomplishment. Clear examples of this success include large numbers of high impact publications (see below), significant impact on UK biomedicine and substantial grant income. In addition, under the NCCRCD training initiative, UCL and NHS partners now host 111 Academic Clinical Fellows, 48 Clinical Lecturers and 17 Clinical Senior Lecturers. 

 

Major organisational changes in UCL Biomedicine since RAE 2001

Integration across UCL has been facilitated by major structural change since 2001. Then, UCL Biomedicine consisted of two Faculties (Clinical Sciences – FCS and Life Sciences - FLS) plus five recently incorporated Research Institutes of which 4 were separately submitted to RAE2001. The opportunity to optimise integration and multidisciplinary working culminated in the 2005 Provost’s Review (Chair: Professor Sir Keith Peters).  As a result, the FCS and Research Institutes were amalgamated in 2006 as the FBS, with 13 thematically based research Divisions/Institutes.  The new FBS, led by Professor Ed Byrne, building on the foundations of the last few years has developed many cross-Faculty collaborative ventures in research and teaching.  The Provost’s review of Life Sciences followed in 2006 (Chair: Professor Alan North) and resulted in the formation of two main FLS Divisions. Co-ordination of research and teaching between FBS and FLS has been achieved by the creation of the UCL School of Life and Medical Sciences, with the aim of delivering a joint strategy.  

 

 

RESEARCH VITALITY UoA4

Key Statistics

 

  • 306 category A staff
  • 5 geographical sites
  • 7 partner NHS Trusts
  • 3 Biomedical Research Centres
  • 30,000 m2 research space
  • £286 million research income 2001-2007

 

 

Clinical impact: new diagnostics and treatments


 

Note: Here as elsewhere  superscript ‘C’ relates to Category C staff; superscripts without a prefix refer to ‘Major Achievements’ listed below under Research Structure and Achievements and those prefixed ‘O’ relate to RA2 publications by specific authors. Underlining of staff names indicates Early Career Researcher. 

 

Gene and stem cell therapy

·       Successful somatic gene therapy for X-linked and ADA-deficient severe combined immuno-deficiencies (Thrasher).

·       First gene therapy trial for eye disease (Ali).

·       Stem cell therapy for ocular surface disease (Daniels).

·       Phase III trials in cancer cachexia and gene therapy for cardiovascular disease arising from Martin patentsO1&2.

 

Other novel therapies

·       First robust demonstration of the clinical benefits of biventricular pacing in chronic heart failure (McKenna110).

·       First 59 cases of non-invasive percutaneous pulmonary valve replacement in children (BonhoefferC13).

·       Identification of the renoprotective effects of eprosidate in systemic amyloidosis (Hawkins80).

·       First treatment for high risk proliferative vitreoretinopathy (Khaw).

·       MRC trial for per-operative control of scarring has influenced treatment worldwide (Khaw).

·       Identification of IL-1 antagonism as new treatment for Neonatal Onset Multisystem Inflammatory Disease and Muckle-Wells syndrome (Hawkins)81.

·       First international multicentre randomised controlled trial of neonatal cooling to prevent perinatal hypoxic ischaemic injury (Wyatt16).

 

Advances in diagnosis and management

·       Risk algorithm to predict sudden death in hypertrophic cardiomyopathy (HOCM), now part of US, European and UK-NSF management guidelines (McKenna). 

·       Establishment of national network for the identification, genetic testing and treatment of familial hypercholesterolaemia informing NICE guidelines (Humphries).

·       More accurate diagnosis of amyloidosis subtypes leading to individualised therapy (Hawkins).

·       Discovery that phytosterolaemia is the single cause of Mediterranean macrothrombocytopenia; now successfully treated with low-sterol diet (StewartO2). 

·       Sentinel node biopsy as the preferred method for breast cancer staging per-operatively (Ell137).

·       Demonstration that infant formula feeding predisposes to later development of insulin resistance and vascular dysfunction (LucasC4).

·       Molecular detection of micro-metastases in gynaecological cancer (Jacobs9).

·       Development of first comprehensive biostatistical data on UK childhood obesity (ColeC43).

 

 

Publications

 

Numbers of high impact publications published by staff in UoA4 are listed in TABLE 2. 

 

TABLE 2: High impact publications (generally IF ≥ 10)

JOURNAL

Number returned in RA2

Not returned including reviews

Nature Journals*

64

28

Lancet

63

28

Blood

35

13

Circulation

31

39

PNAS

28

3

Am J Human Genetics

22

4

New Eng J Med (NEJM)

14

6

Gastroenterology

13

1

J Clin Invest

12

0

J Exp Med

9

1

Science

9

1

Neuron

7

1

Cell Journals

6

4

Current Biology

6

2

Other

21

11

Trends and Physiol Reviews

0

31

 

 

 

TOTAL

341

172

 

* Including 18 in Nature

 

 

 

 

 

Duplication of outputs

There are 15 duplicates in UoA4. Of these, 9 are multidisciplinary outputs in Nature journals, 2 in PNAS, 2 in Cell journals,1 in the Lancet and 1 in J Clin Oncol. 

 

Income

Despite the major reconfiguration of UoAs between RAE2001 and RAE2008, research funding for the 3 main research clusters of Children’s and Women’s Health, Special Senses and Experimental Medicine (see below) can be compared in the 2 assessment periods. In RAE2001, research income was £142 M (260 Category A); in RAE 2008 it has risen to £286M (306 Category A). Yearly totals are given in Table 3. The 2003-2004 peak is largely attributable to Joint Infrastructure Fund (JIF) monies. Total JIF and SRIF2 amounts to £17.5M. From 2002 to 2007, net of JIF there was a 40% increase in income (15% from 2006 to 2007). OSI Research Council income increased by 45%, NHS R+D support has trebled and UK Government income quadrupled. In 2007 the average research income per Cat A returnee was £160K.

 

TABLE 3: Research Income

Year

2002

2003

2004

2005

2006

2007

Total

Income £M

38.6

43.3

46.3

41.2

43.1

49.0

285.7

 

Substantial programme-type funding (awards of 4 years or longer) of over £153M was held during the assessment period, 65% from Research Councils, Wellcome Trust, BHF, CRUK and Foundation Fighting Blindness. Infrastructure support to maintain the high research activity and impact amounted to £81M in new facilities, laboratory refurbishment and major items of equipment (2001-2007). Current grants and contracts are over £186M, positioning us to advance our strategy.

 

Early career investigators 

Fifty five early career investigators entered the profession after August 2003 and 34 of these after August 2005. Three are funded by the Royal Society, 17 by other charitable or Research Council fellowships (including 5 Wellcome Trust awards), 2 have MarieCurie awards and 2 hold HEFCE Clinical Senior Lectureships.

 

 

RESEARCH STRUCTURE AND ACHIEVEMENTS

 

The six Divisions/Institutes of UCL’s FBS returned in UoA4 are horizontally and vertically linked.  Horizontal linkage is achieved through a number of common overarching themes, and vertical linkage is via three research clusters, and the return will be structured around these overarching themes and research clusters.

 

The OVERARCHING THEMES are;

 

·        Genetics

·        Gene therapy

·        Neurocognition

·        Regenerative medicine and stem cells

·        Imaging

·        Life-long health

 

The RESEARCH CLUSTERS are;

 

·        Children’s and Women’s Health: Institute of Child Health and Institute for Women’s Health. (140, 25, 18 and 1 Category A, B, C and D staff respectively)

·        Special Senses: Institute of Ophthalmology and the Ear Institute (61 and 5 Category A and B respectively)

·        Experimental Medicine: Division of Medicine and Division of Surgical and Interventional Sciences and collaborators in the Faculty of Life Sciences. (105, 11 and 3 and 1  Category A, B, C and D staff respectively)

 

OVERARCHING THEMES

 

GENETICS

Genetic analysis connects much research across UoA4 and Humphries leads a UCL-wide Genetics Consortium. Novel disease genes have been identified in many conditions and insights into the functional consequences of mutations are growing rapidly. Disorders studied include:

NEUROLOGICAL CONDITIONS: epilepsy (Clayton1, EverettO1&2, GardinerO1&2), neurodegeneration (ClaytonO4, RahmanO1,ShimaO3), behavioural disturbance (Skuse40), speech/language disorders (LiegeoisO3, Vargha-Khadem).

CARDIOVASCULAR DISORDERS: cardiomyopathy (ElliottO4, McKenna95&96, Syrris95,O1-4), warfarin resistance (Tuddenham100), haemolytic anaemia (Stewart)100, hypertension (HayworthO4, Unwin129).

SENSORY DISORDERS: cataract (Bhattacharya63, HardcastleO2), retinal degeneration (Bhattacharya63,O3, CheethamO3&4, HardcastleO3&4, HuntO2&4, Moore ATO2-4, Webster64,O1), deafness (Bitner-GlindiczO1,DawsonO1&2 , DiO3, ForgeO2), developmental eye disorders (Hennekam23,O4), pain (GardinerO4).

INFLAMMATORY DISEASE: Crohns immunodeficiency (Forbes119), congenital neutropenia (AncliffC-O1&2), sarcoid (HillO2).

MISCELLANEOUS: malformations (Bitner-Glindzicz27, ChungO2&3, Hennekam23,O2, KletaO4, MitchisonO2 Scambler PJ22,O4, StanierO4), endocrine disorders (AchermannO3, BoulouxO4, Cheetham55, Dattani3:O1,2,4), ovarian cancer (GaytherO1,2,4), renal aciduria (Kleta126,128).

 

Progress has been made in understanding epigenetic mechanisms in placental function (Moore GE) and stem cell development (Widschwendter). Animal models have indicated a role for ciliary defects in Bardet Biedl syndrome (Beales) and enabled novel therapy development for spina bifida (Copp). DNA testing in Familial Hypercholesterolaemia (Humphries) has influenced NICE guidelines. Common functional genetic variants have been shown to increase risk of coronary artery disease (Humphries) and left ventricular hypertrophy (Montgomery). UCL houses a unique network of cohort studies (>30,000 subjects) with genotypic and multiple phenotypic measures relevant to cardiometabolic, respiratory, and cognitive disorders for gene discovery and gene replication studies; using the technique of “Mendelian Randomisation”, genotype-phenotype relationships have been examined to assess the causal relevance of traits for disease risk (Hingorani). 

 

GENE THERAPY

This is a rapidly evolving area, with major advances at UCL since 2001 using multidisciplinary research spanning basic vector design, preclinical gene therapy development and clinical trials. The UCL Gene Therapy Consortium incorporates investigators from UoA4 with those in the Cancer Institute (Linch and Nathwani, UoA2) and in Infection and Immunity (Stauss, UoA3). The breadth of research embraces ophthalmology (AliO1,2&4, BainbridgeO1,2&4, MacLarenO4), immunology34 (GasparO2&4, QuasimO4, ThrasherO1-3), cardiovascular and haematology (DavidO2, GustafssonO4, HartO4, KinnonO2,OwenO1), muscle (PeeblesO4), liver (HodgsonO3, TuddenhamO4, WaddingtonO1-4) and oncology (Anderson WJO3). Additional studies address virus integration PhilpottO1&2 and vector development (Thrasher and Ali34 and gene delivery DavidO2&4).UCL dominates UK academic development of gene therapy, providing all the non-commercial Gene Therapy Trial Proposals to the DoH Gene Therapy Advisory Committee in 2006.  Two of the four UK specialist gene therapy companies were founded at UCL (Martin) and four of the eight recent DoH awards for gene therapy development, patient monitoring and safety went to UCL. To enhance developments, the Wolfson Centre for Gene Therapy of Childhood Disease opened at ICH in 2005.  Translation via a GMP-grade clinical gene therapy laboratory has led to successful clinical therapy for X-linked Severe Combined Immunodeficiency (SCID) and for ADA-deficient SCID (Thrasher, Gaspar).  The joint appointment at IO/ICH of Ali secured £1M DoH funding for the first clinical trial of gene therapy for retinal degeneration (started Feb 2007). Martin has pioneered VEGF-based gene therapy to prevent peripheral vascular re-stenosis. Tuddenham has developed gene vectors for factor IX to treat haemophilia with clinical studies to start in 2008.

 

REGENERATIVE MEDICINE AND STEM CELLS

This theme includes initiatives in eye disease (IO), hepatology, cardiovascular and musculoskeletal science. Stem cell research is consolidated across UCL and linked to the MRC’s NIMR by the UCL Centre for Stem Cell Research (Stern, UoA14), which includes nearly 100 investigators. IO has the first UK MHRA-accredited lab for human stem cell transplantation to treat patients with limbal stem cell failure (DanielsO4). Immortalized cells (Greenwood), stem cells (Coffey) and photoreceptor progenitor cells (MacLaren, Pearson, Ali & Sowden) have been used to treat retinal disease. Strength in this area is reflected by 4 MRC grants. Coffey leads on the London Project, an £8M programme to develop stem cell therapy for age-related macular degeneration. Elsewhere, stem cell programmes exist in liver regeneration (Hodgson), amyloidosis (Hawkins), acute myocardial infarction (Martin), haematology (AmroliaO3&4), urology (De CoppiO3,4) and musculoskeletal disease (Mudhera, MarshO1, Morgan).

 

NEUROCOGNITION

This theme arises out of links between specific areas (child health, vision and hearing) and complements activities in clinical and fundamental neuroscience (FBS and FLS - UoA9). Interdisciplinary studies combine the genetic basis of abnormal cognitive function (Skuse40, Shaw-SmithO3), the impact of acquired perinatal injury (Robertson, Gadian), rehabilitation following childhood traumatic brain injury (Vargha-Khadem) and development of facial perception (De HaanO1-3). Evolutionary concepts of vision have challenged traditional views of visual perception (Lotto62). Sillito57 and Carandini61 have developed understanding of central visual processing while Bex59,O1-4 and DakinO1-4 have advanced visual psychophysics including perception of natural scenes. Processing spatial and intensity coding of auditory stimuli are central to the investigations of ChaitO1-4,DeanO1, McAlpine71,72 and Ashmore70. The first detailed description of auditory receptive fields in the mouse will facilitate auditory studies in genetically modified animals (LindenO1).

 

IMAGING

Imaging in many modalities permeates UoA4, with benefit from close working with the Functional Imaging Laboratory (Dolan UoA9) and the UCL Centre for Medical Image Computing (Hawkes). Retinal autofluorescence imaging has been pioneered (FitzkeO2&3) and apoptosis visualised in the living retina (Cordeiro58). Structural and functional neuroimaging during development has yielded novel findings on cortical plasticity in childhood epilepsy (BaldewegO1CrossO1,2&4) and genetic disorders of speech and language (LiegeoisO3, GadianO2). Studies of high field MRI of neonatal encephalopathy has been reported (HagmannO2). ClarkO1-4 is advancing white matter imaging. A BHF Centre for Cardiovascular Imaging (Taylor AMO2&4) enables functional studies of congenital heart disease and has supported non-surgical heart valve replacement (BonhoefferC,13). The Institute of Nuclear Medicine (Ell) has the UK’s first 32 and 64 slice PETCT scanners for myocardial perfusion and molecular imaging studies.

 

LIFE-LONG HEALTH

Multidisciplinary research spans conventional age categories and relates early-stage genetic and environmental influences to health and risk of disease in later life.  A ‘cradle-to-grave’ approach in cardiovascular research has identified genetic and environmental risk factors for childhood atherogenesis (DeanfieldC), and sudden cardiac death in HOCM (McKenna). Early nutrition, particularly the first weeks after birth, determines the risk of cardiovascular disease, obesity and type 2 diabetes in adulthood (Singhal).  Transgenerational effects of maternal smoking on childhood lung development (Dezateux) and factors affecting mother-to-child HIV transmission (NewellC) are other examples.  An epidemiological and biostatistical synthesis is provided by analysis of birth cohorts, for example the multi-generational 1958 cohort (Power), and by construction of population data on the development and health effects of obesity across the life course (ColeC).  There are research programmes in diseases of adolescence and young adults (Viner O1-4), linking into the common chronic diseases of adulthood, including hypercholesterolaemia, type 2 diabetes (BetteridgeO1-4), obesity (BatterhamO4), hypertension (MacAllister O1) and in later life, osteoporosis (Arnett O1-4) and fragility fractures (Marsh O1,4). 

 

 

RESEARCH CLUSTERS

 

CHILDREN’S and WOMEN’S HEALTH: Institute Of Child Health and Institute For Women’s Health

 

Introduction

The Institute of Child Health (ICH; Director: Copp), the largest centre for child health research in Europe, houses a comprehensive range of disciplines and techniques to enhance understanding, prevention and therapy for childhood disease. ICH shares a site with GOSH and together they form an SBRC (£7M pa).

 

The Institute for Women’s Health (IWH; Director: Jacobs), created in 2004, pursues research in reproductive health and gynaecological cancers and collaborates with ICH in fetal medicine and neonatology research. IWH is closely integrated with UCLH, and forms the Women and Neonates research theme of UCL/UCLH’s CBRC (£16.5M pa).

 

Joint grant income during the assessment period was ~£146M.

 

Research Infrastructure

ICH and IWH occupy 12,750m2 of laboratory space, comprehensively underpinned by technicians and other support staff. Developments and enhancements to core research infrastructure include:

 

·        Affymetrix microarray and cell sorting facilities upgraded to enable a range of cell separation and gene chip analyses. An Illumina sequencing platform will be added in 2008.

·        Cardiac MRI facility (2,100m2; BHF and GOSH Special Trustees, £8.4M) providing cardiac imaging and research catheterisation lab.

·        Children’s Clinical Research Facility (650m2; GOSH Special Trustees, £1M). UK’s first dedicated paediatric facility will open Feb 2008.

·        Clinical and Molecular Genetics laboratories (420m2; GOSH Special Trustees, £3.4M), opened in 2006. Facilitated recruitment of Hennekam and Moore GE).

·        Infectious Disease and Immunology Centre incorporating Wolfson Centre for Gene Therapy of Childhood Disease (1,050m2; Wolfson Foundation, £1.5M; GOSH Special Trustees £4.9M; SRIF1/2, £7.9M). Opened in 2006, providing Category 3 microbiology facilities, enabled recruitment of Crompton.  

·        Proteomics Laboratory (200m2) to facilitate IWH research into identification of novel biomarkers. Q-TOF and SELDI-TOF mass spectrometers obtained in 2005-6 for ICH.

·        Tissue Engineering Laboratories (230m2 space; Royal Society and ICH, £0.9M).

·        Translational Research Laboratory linked to a Clinical Research Unit (2004), houses UKCTOCS/UKFOCSS ovarian cancer screening trials (£2M).

·        Wolfson Centre for Gene Therapy of Childhood Disease (see Overarching Themes, above).

 

Research Groupings and Achievements

Research is organised into 10 Research Groups, reflecting the most important issues affecting women and children’s health and Government/NHS R+D priorities. Each group is led strategically by a scientist of international standing, working with research-active clinicians. This integrates basic and clinical research, and ensures participation from hospital staff.  

(A) Biochemistry, Nutrition & Surgical Sciences (LucasC)

(B) Cancer (Jacobs)

(C) Cardiac & Respiratory Sciences (Mythen)

(D) Fetal & Neonatal Medicine (Peebles)

(E) General & Adolescent Paediatrics (Taylor BW)

(F) Genes, Development & Disease (Scambler PJ)

(G) Infection & Immunity (Kinnon)

(H) Neurosciences & Mental Health (Koltzenburg)

(I)  Population Health Sciences (Dezateux)

(J) Reproductive Health (Stephenson: returned to UoA6)

 

 

(A) Biochemistry, Nutritional & Surgical Sciences 

Founded on the effects of genetic and environmental factors on children's nutrition, metabolism and endocrinology in health and disease. Long-term funding from MRC Programme Grant (£4.6M LucasC and Singhal). Recruits include Achermann (Wellcome Trust Senior Clinical Fellow), Rahman (HEFCE Clinical Senior Lecturer), De Coppi and Mills.

 

Major achievements:

1.      Pyridoxamine 5'-phosphate oxidase deficiency causes neonatal epileptic encephalopathy (Clayton, Hum Mol Genet), while antiquitin deficiency causes pyridoxine-dependent seizures (Clayton, Nat Med).

2.      Short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency in hyperinsulinism (Eaton, J Clin Invest).

3.      HESX1, SOX2 and SOX3 cause hypopituitarism with forebrain defects (Dattani, Development, J Clin Invest x2, Am J Hum Genet).

4.      Rapid neonatal growth predisposes to later development of insulin resistance and vascular dysfunction (LucasC, Lancet), while childhood breast feeding improves lipoprotein profile in teenagers (Singhal, Lancet).

5.      Pluripotential stem cell line from amniotic fluid developed enabling surgical tissue engineering (De Coppi, Nat Biotech).

 

(B) Cancer 

Strengthened by recruitment of Jacobs’ gynaecological cancer group, with MRC Programme Grant support (£7.3M), a key part of the IWH strategic development. Research encompasses cancers of women and children, including haematological paediatric and gynaecological cancers. Research ranges from laboratory based studies (£1M support from Children with Leukaemia) to the largest ever randomised clinical trial (UK Collaborative Trial of Ovarian Cancer Screening; 202,000 women). Anderson WJ and Widschwendter became HEFCE Clinical Senior Lecturers in 2006. 

 

Major achievements:

6.      Identification of immune modulation and oncogenesis due to PAX3-FKHR gene fusion (Anderson WJ, J Exp Med).

7.      Role of TEL-AML and MLL-ENL translocations in pre-leukemia and haematopoietic progenitor immortalisation (Williams O, Brady, Blood, Cancer Res).

8.      Epigenetic stem cell signature in cancer (Widschwendter, Nat Genet). 

9.      Molecular detection of micro-metastases in gynaecological cancer (Jacobs, Lancet).

10. ErbB-2 overexpression, mitogenic signalling and cell cycle progression in human breast luminal epithelial cells. (Timms, Oncogene).

 

(C) Cardiac & Respiratory Sciences

Strengthened by the recruitments of BonhoefferC, Taylor AM and Walker SM, and jointly between ICH and Medicine, McKenna and Elliott.  Research ranges from genetics and cell biology of congenital heart disease to evaluation of risk factors for adult vascular and respiratory disease. Supported by MRC Career Establishment Grant (£702K, Riley) and BHF programmes (£806K, Anderson RH; £762K, DeanfieldC; £888K, BonhoefferC).

 

Major achievements:

11. Identification of a novel cardiac stem cell population that can generate new vessels in the heart (Riley, Nature).

12. Link between childhood obesity and arteriopathy through a novel role for leptin in arterial distensibility (DeanfieldC, Circulation).

13. First 59 cases of non-invasive percutaneous pulmonary valve replacement in children (BonhoefferC, Circulation x2; JACC), with development of a commercial contract (Medtronic).

14. Relief of post-surgical right ventricular outflow obstruction by percutaneous pulmonary valve replacement (Taylor AM, Circulation).

15. Non-screened infants with cystic fibrosis have airway obstruction at diagnosis, persisting despite therapy (Stocks, Lancet; WallisC, Am J Resp Crit Care Med).

 

 

(D) Fetal & Neonatal Medicine 

Perinatal research was strengthened by recruitment of Raivich, Robertson and David (DOH Clinical Senior Lecturer). Multidisciplinary research includes approaches to causes and management of perinatal brain injury, viral vectors to deliver therapeutic genes to the fetus or uteroplacental vasculature, and non-invasive prenatal diagnosis from circulating free-fetal DNA. 

 

Major achievements:

16.Development of neuroprotective hypothermia for perinatal hypoxic ischaemic injury (Robertson, Ann Neurol) and successful first international multicentre randomised controlled trial of neonatal cooling (Wyatt, Lancet).

17.Role of AP-1 transcription factor c-jun in axon regeneration (Raivich, Neuron).

18.Ultrasound guided gene therapy for fetal airways and vasculature in utero (Peebles, Gene Ther; David, Human Gene Ther).

 

(E) General & Adolescent Paediatrics           

This new grouping reflects the commitment to excellence within primary/secondary paediatrics and in the tertiary/specialist GOSH-based area. Research focuses on adolescents, immunisation, and an interdisciplinary collaboration on obesity.

 

Major achievements:

19.Effectiveness of meningococcal C conjugate vaccine in teenagers (Viner, Lancet) and meningitis risk after MMR vaccine (Taylor BW, Am J Epidem).

20.Health outcomes after assisted conception (Sutcliffe, Lancet).

21.Adult health/social outcomes of children in public care (Viner, Pediatrics).

22. Therapeutic equivalence of medical and surgical management of vesicoureteric reflux (Woolf, Lancet).

 

(F) Genes, Development & Disease 

Clinical genetics research integrates with human molecular genetics and animal models to identify causes and predisposing factors of childhood disease. A focus is on genetic syndromes, ciliary disorders and renal anomalies in which developmental studies explore mechanisms of genetic disease. Recruits include Hennekam, Moore GE and Stanier. Supported by BHF programme grant (£554K; Scambler PJ) and Wellcome Trust Clinical Senior Fellowship (£1.5M; Beales).

 

Major achievements:

23. Mutation of intraflagellar transport protein IFT80, causes Jeune asphyxiating thoracic dystrophy  (Scambler PJ, Nat Genet) and two genetic causes of Fraser Syndrome (Scambler PJ, Woolf, Nat Genet x2).

24. B3GALTL mutated in Peters Plus syndrome, and CBP and EP300 are alternative causes of Rubenstein Taybi syndrome (Hennekam, Am J Hum Genet x2).

25. Novel, non-Mendelian inheritance in Bardet-Biedl (BBS) syndrome (Beales, Science).

26. Causative BBS genes regulate primary cilia function (Beales, Nature) and determine epithelial polarity in the embryo (Beales, Nat Genet).

27. Uroplakin-IIIa mutations in renal dysplasia (Bitner-Glindzicz, J Am Soc Nephrol).

28. Limited conservation of genomic imprinting between humans and mice (Monk, PNAS) and exclusion of STOX1 in pre-eclampsia (Moore GE, Nat Genet).

 

 

(G) Infection & Immunity 

Child-orientated research closely integrates with UCL’s adult-focused immunology and rheumatology research (UoA3). Focus is basic molecular and cellular mechanisms, genetics and epidemiology of infectious disease and immunological disorders in children. Translational research covers development/evaluation of vaccines, improvement of bone marrow transplantation, and implementation of gene therapy for immunodeficiency diseases. Recruits include Crompton, Londei, Qasim (£361K; Leukemia Research Fund Senior Lecturer) and Philpott. Supported by Wellcome Trust Clinical Senior Fellowship (£1.5M; Thrasher).

 

Major achievements:

29. Novel role for hedgehog signalling in T lymphocyte development (Crompton, Blood x2).

30. Prevention of experimental arthritis by B lymphocytes producing interleukin 10 (Londei, J Exp Med).

31. Clinical regimens improving survival and diminishing graft vs host disease after unrelated donor bone marrow/T cell transplantation (VeysC  Blood; Amrolia, Blood).

32. Mannose binding lectin diminishes febrile neutropenia in paediatric cancer chemotherapy (Klein  Lancet).

33. HIV influence on response to pneumonia treatment in S Africa (Goldblatt, Lancet).

34. Successful somatic gene therapy for X-linked severe combined immuno-deficiency (Gaspar, Lancet), ADA-deficient SCID (Kinnon, Mol Therapy), and non-integrating lentiviral vectors to reduce risk of insertional mutagenesis (Thrasher, Ali, Nat Med).

 

(H) Neurosciences & Mental Health 

Research centres on the nervous system throughout development, using molecular and cell biology, systems neuroscience and clinical investigation. Developmental neurobiology, cognitive neuroscience, neuroimaging, pain research and clinical paediatric neurology are all strengths. Includes new MRC Centre for Neuromuscular Disease (joint with Inst. Neurology - UoA9). Recruits include: Clark and Hobson. Supported by programme grants from MRC (£385K; Vargha-Khadem) and Wellcome Trust (£1.1M; Copp), and Wellcome Trust Career Development Fellowships (£437K; McSweeney, £587K; Martinez-Barbera).

 

Major achievements:

35. FOXO transcription factors regulate neuronal cell death (Ham, J Cell Biol), and development of pain-related neuronal subtypes (Koltzenburg, J Neurosci).

36. Molecular pathways activated by folic acid (Greene, Brain), including Cited2 (Martinez-Barbera, Hum Mol Genet), and spina bifida prevention by a novel factor, inositol, leading to clinical trial (Copp, Hum Mol Genet).

37. Detection of low nocturnal O2 saturation in sickle cell crises, generating a clinical trial to prevent childhood stroke (Kirkham, Blood). 

38. Hippocampal enlargement after status epilepticus, a prognostic feature for long-term epilepsy (Scott, Brain).

39. Selective memory anomaly after early hypoxic-ischemic brain injury, and MRI correlates of FOXP2-related speech and language disorder (Vargha-Khadem, Nat Neurosci, Brain, PNAS).

40. Critical X-linked loci for cognitive function in Turner syndrome, and for amygdala development and fear recognition (Skuse, Nat Genet, Brain).

 

(I) Population Health Sciences 

Research encompasses epidemiology and biostatistics of childhood health and disease with emphasis on cohort studies, clinical trials in international health interventions, and development of public health policy. A key aspect of the multi-disciplinary approach in children's and women's health, interacting closely with many other areas including UCL’s adult-orientated Public Health grouping, returned to UoA6. Includes new MRC Centre of Epidemiology for Childhood Disease (£1.7M; Head: Dezateux) with MRC Programme Grant support (£380K; ColeC) and Career Development Awards from DOH (£324K; Hypponen) and Wellcome Trust (£648K; Osrin), both early career investigators.

 

Major achievements:

41.Population data and factors affecting childhood amblyopia and severe visual impairment in UK children (Rahi, Lancet x2).

42. Health inequalities and child growth trajectories in 1958 cohort (Power, BMJ, Am J Clin Nutr).

43. Biostatistical data on childhood obesity in the UK (ColeC, BMJ) and links between infant growth and obesity in later life (Law, BMJ).

44. Factors affecting HIV transmission from mother to child (NewellC, Lancet).

45. Maternal smoking and child lung function (Dezateux, Am J Resp Crit Care).

46. Improved maternal and neonatal mortality after introduction of local women’s groups in Nepal (Costello, Osrin, Lancet).

 

(J) Reproductive Health 

New grouping within IWH covering research on oocyte maturation and causes of aneuploidy, clinical studies in adolescent gynaecology, rare disorders of sexual development and reproductive health in chronic disease. Well integrated with Public Health, via new recruit Stephenson (UoA6) and strengthened by recruitment of Homer and Fitzharris.  

 

Major achievements:

47.Granulosa cell homeostatic influences on oocyte maturation (FitzHarris, Development).

48.Prevalence and prognosis of endometrial cancer in women with polycystic ovaries (Hardiman, Hum  Reprod).

49.Altered arterial visco-elastic properties as evidence for vascular dysfunction in polycystic ovary syndrome (Hardiman, Circulation).

50.Outcome of conception in patients treated by stem cell transplantation in 229 European centres (Chatterjee, Lancet).

 

Developments Highlighted in RAE2001

The intention of RAE2001 to create improved research facilities at ICH has been fully realised with the building of 700 m2 of new lab/office space and the refurbishment of a further 3,950 m2. RAE2001 anticipated a multidisciplinary approach to identifying the molecular basis of inherited childhood disease achieved by the bringing together of geneticists, molecular biologists and developmental biologists in the Jeans for Genes Centre for Childhood Inherited Disease, with success in integrated research24,36 .

 

Development of an integrated cardiovascular research programme has progressed beyond expectations with the establishment of the UCL Cardiovascular Sciences Institute, of which ICH/GOSH forms the child/developmental part.  This venture will enable integration of child- and adult-based cardiovascular research with molecular, cellular and developmental cardiology. 

 

The importance of child nutrition influencing lifelong health was a priority area identified in RAE2001. Indeed, the publication of two Lancet papers in 2004, reporting the importance of neonatal growth rate to determine future cardiovascular health (LucasC, Singhal), has established this research strength at ICH and has opened up a major industrial collaboration (with Abbott). 

 

In child public health, an aim of RAE2001 was to strengthen ICH’s research in health promotion in developing countries. Success in the area of HIV epidemiology was enhanced by the 5-year secondment of an ICH professor (NewellC) as head of the Wellcome Trust Africa Centre.  Moreover, field research in Nepal (Lancet) has identified a novel, low cost intervention, based on local women’s groups, that diminishes infant and maternal mortality (Costello). This work has encouraged the development in 2007 of a UCL Global Health initiative, led jointly by ICH and UCL Public Health (returned to UoA6).

 

 

SPECIAL SENSES: Institute of Ophthalmology and Ear Institute

 

Introduction

The Institute of Ophthalmology (IO; Director: Luthert) and the Ear Institute (EI; Director: McAlpine) aim to understand basic sensory processes and related diseases.  The IO is one of the most influential and productive centres for research into vision and eye disease in the world and is situated on the same site as MEH with which it shares SBRC status.  The EI is the largest grouping of auditory scientists, clinicians and audiologists in Europe. It was constituted in January 2005 with the opening of the JIF-funded Centre for Auditory Research adjacent to the Royal National Throat Nose and Ear Hospital (RNTNEH). This brought together researchers from across UCL investigating hearing and deafness.  

 

Joint grant income in the assessment period was £52M.

 

Research Infrastructure

IO and EI occupy 7,800m2 of laboratory space with comprehensive support from technical and clerical staff. Recent developments and enhancements include;

 

·        Centre for Auditory Research (£11M; JIF/Wellcome Trust)  

·        Auditory laboratory for digital signal generation and sound testing

·        Clinical laboratories for testing human auditory function including electro-encephalography.  

·        Imaging suites, including SEM and TEM, multiphoton and confocal microscopes,  and laser capture microscope.

·        Sound-proof and anechoic chambers for human and animal experimentation

·        Translational Eye Research building (£9.2M, JIF/Wellcome Trust, 2003 with £1m budget for equipment). 

·        UK MHRA-accredited lab for human stem cell transplantation, used for limbal stem cell transplantation therapy at MEH (£0.3Mk).

·        Visual function suite including behavioural testing rooms, ERG, SLOs, OCT and fluorescein angiography (£0.3M upgrade in 2007)

·        Functional genomics and sequencing facilityequipped 2006 (£0.8M)

 

Research Groupings and Achievements

Research groupings at IO were redefined to strengthen multidisciplinary working and reinforce our translational strategy. The themes for the two institutes are as follows:

 

(A) Cell Biology and Cellular Therapy

(B) Visual Neuroscience

(C) Genetics and Molecular Therapy

(D) Ocular Repair and Regeneration

(E) Inner Ear and the Hearing Brain

(F) Genetics of Hearing and Deafness

 

(A) Cell Biology and Cellular Therapy 

This group (created 2001) provided the focus for an MRC cooperative (£266K). Supported by programme grant funding including Wellcome Trust (Greenwood, £0.7M, Moss, £0.8M) and MacTel Project (Greenwood & Moss, £0.9M). New recruits are Fruttiger, Ruhrburg (previous MRC Fellow), Coffey, Turowski, and Niccol (nee van der Spuy).

Major achievements:

51.Discovery of a phosphatidic acid sensing transcription factor; demonstrated that inner membrane surface charge alters during phagocytosis and identified an ER targeting sequence (Levine, Science x2; EMBO J).

52.Novel signalling pathways by which epithelial tight junctions regulate cell proliferation, gene expression and activation of RhoA signalling mechanisms (Balda and Matter, J Cell Biol; EMBO JDev Cell).

53.Roles of VPS34 and annexin 1 in biology of multivesicular endosomes (Futter, J Cell BiolEMBO J), requirement of Annexin 11 for midbody formation and completion of cytokinesis. (Moss,  J Cell Biol), roles of annexin5 in apoptosis (Moss, PNAS) and annexin 2 in actin dynamics (Moss, EMBO J; Current Biology). 

54.First successful use of immortalised human RPE (Greenwood, PNAS; Coffey, Nat Neurosci).

55.Identification of novel cofactor and putative chaperone for ACTH receptor causing inherited glucocorticoid deficiency (Cheetham, Nat Gen).

56.DNAJ molecular chaperone, a proteosomal sorting factor, highlighting potential role in human misfolding diseases (Cheetham, Current Biology).

 

(B) Visual Neuroscience

Visual neuroscience has developed in central visual processing, psychophysics and retinal imaging, with links to the Gatsby (UoA9). New recruits Cordeiro and Carandini. MRC Programme funding (Sillito £1.5M).

 

Major achievements:

57.Redefining the role of corticothalamic feedback in vision (Sillito, Salt, Nat Neurosci;  Sillito, PNAS).

58.First visualisation of retinal ganglion cell death in vivo and identification of link between Alzheimer's Disease and Glaucoma (Cordeiro, Fitzke PNASx2).

59.Demonstration that dynamic tuning of orientation-specific single neurons in visual cortex does not reflect the behaviour of populations of cells (Bex and Dakin, PNAS).

60. Demonstration that cichlids tune the spectral sensitivity of cones by differential expression of opsins (Bowmaker, Current Biology).

61.Landmark investigations of contrast and luminance processing and pre-cortical and cortical processing of visual information (Carandini, Neuron x2, Plos Biol, Nat Neurosci).

62.Elucidation of colour vision mechanisms: implications for understanding effect of light source on human perception (Lotto, PNAS x2, Current Biology). 

 

(C) Genetics and Molecular Therapy 

First gene therapy trial for retinal degeneration (Ali) and further genes causing a variety of eye diseases have been identified. Health Foundation Fellowship (MacLaren £0.7M), Wellcome Trust Fellowship (Bainbridge and Royal Society Fellowship (Pearson). New recruit Ohnuma. Support includes DoH (£0.9M Ali), Foundation Fighting Blindness (£1.9M joint with Visual Neuroscience Fitzke) and Wellcome Trust (£0.6M Hunt programme funding.

 

Major achievements:

63.First splicing factor gene (PRPF31) cloned for ADRP (Bhattacharya, Mol Cell); and novel genes for congenital posterior polar cataract cryab (Bhattacharya, Am J Hum Genet); ADRP TOPORS and PRPF3 (Bhattacharya, Am J Hum Genet; Hunt, Hum Mol Genet).

64. Mutation in the gene KCNV2 encodes a voltage-gated potassium channel subunit that causes cone dystrophy (Webster, Am J Hum Gen); demonstration of olfactory and cerebral abnormalities in PAX6 deficiency (Moore GE, Nat Gen).

65. First demonstration of functional integration of rod precursors into adult retina (MacLaren, Pearson, Sowden, Ali  Nature).

66.Role of ATP release from RPE in retinal development (Neuron, Pearson). 

 

(D) Ocular Repair and Regeneration 

Internationally known for research in prevention of scarring following glaucoma surgery. New recruits are Shima and Daniel

 

Major achievements:

67.First use of dendrimer therapy to inhibit scarring (Khaw, Nat Biotech).

68.Role for diaphragm protein PV-1 in endothelial fenestra morphogenesis and elucidation of mechanisms of Golgi membrane fusion (Shima, PNAS, J Cell Biol).

69.VEGF164-mediated inflammation in pathological neovascularization and clarification of the mechanism of action of Macugen, the first successful aptamer therapy for intraocular angiogenesis (Shima, J Exp Med; PNAS).

 

(E) Inner Ear and Hearing Brain

Research includes mechanisms of hearing in the cochlea, neural processing of complex sounds from auditory nerve to cortex and cerebral mechanisms of spatial hearing.

 

Major achievements:

70.Rapid re-supply of neurotransmitter vesicles at the IHC synapse enabling temporally precise release (Ashmore, Nature).

71.Overturned existing theories of neural coding for auditory spatial cue of interaural time difference; framework to understand coding strategies in spatial hearing (McAlpine, Nature, Marqardt, Nature).

72.Solved the “dynamic range problem” in auditory intensity coding (Dean and McAlpine, Nat Neurosci); functional brain imaging to show that human auditory spatial processing follows principles elucidated from single neuron recordings in small mammals (McAlpine, Nat Neurosci).

 

(F) Genetics of hearing and deafness

This theme focuses on the development and regeneration of the inner ear, the genetics of deafness in humans and animal models, and the molecular genetics of hair cell development.

 

Major achievements:

73. Involvement of planar-cell polarity pathway in Bardet-Biedl syndrome, a disorder associated with ciliary dysfunction that shares phenotypes with PCP mutants (Forge, Jagger, Nat Genetics; collaboration with Beales, ICH). 

74. Role for Notch activity in early formation of inner ear sensory patches (Daudet, Development).

75. Proposed mechanism by which mutation in the POU4F3 gene causes hair cell damage (Dawson, Cell Mol Biol).

76. Demonstrated rapid calcium waves in the cochlea for sensing noise damage in the inner ear (Gale, Curr Biol).

 

Developments Highlighted in RAE2001

To expand imaging and visual assessment, IO recruited Coffey, an international authority on retinal imaging and behavioural assessment of visual function and a clinician scientist (Cordeiro) who has pioneered in vivo retinal imaging of apoptosis. IO’s commitment to the next generation of researchers has seen several junior appointments in cell biology and development (Turowksi, Ruhrberg, Fruttiger, Niccol (nee van der Spuy)). A move into primate work was achieved by collaboration with UCL Anatomy to Ophthalmology (Zeki). RAE2001 emphasised the development and validation of novel ocular therapies an area of substantial success (see major achievements 54, 65 67 and overarching themes). 

 

The anticipated translational eye research building (JIF) was completed and is the focus for translational work with migration of translational groups into adjacent space to optimise access to its facilities. Clinical interface activity has been enhanced by creation of a Clinical Research Facility and Reading Centre in MEH and a research floor in the Richard Desmond Children’s Eye Centre (opened Feb 2007). A successful capital bid to NHS R+D (£2.85M) will fund further development of a Clinical Research Facility at MEH. 

 

 

EXPERIMENTAL MEDICINE

 

Introduction

Experimental Medicine returns related themes of research activity from the Divisions of Medicine (Director: MacAllister) and Surgical and Interventional Sciences and from investigators in the Faculty of Life Sciences at UCL. This research depends on intimate partnerships with UCLH, RFH, RNOH and the WH, and the mission of both Divisions is the performance of innovative, high-quality biomedical research, excellence in undergraduate and graduate teaching, and exemplary patient care. 

 

Grant income in the assessment period was £86M.

 

Research Infrastructure

The grouping occupies 8,618 m2 of high quality laboratory space and benefits from 28 core HEFCE-funded administrative, technical and IT posts. Investment in equipment amounts to £7M.  Recent developments include:

 

·        Angiography suite (BHF, £1M).

·        Centre for Biomedical Science at the Hampstead Campus (Royal Free Trust, £1.3M)

·        GMP facility (forthcoming) for cell-based therapy (RMS-UK, £2M).

·        Hatter Institute redevelopment (Hatter Foundation £5M).

·        Imaging suite including a Biorad 2100, Widefield Microscopy system and TIRFM microscope (BHF/Wellcome Trust £0.6m).

·        Institute of Hepatology new laboratories (Liver Foundation, £1M).

·        Magnetic navigation system for research angiography suite (BHF, £1.4M).

·        Proteomics facility with 2 mass spectrometers (Wellcome Trust, £0.6M).

·        Rayne Building  refurbishment (BHF, £6M).

·        RFH refurbishments 600 m2 (Royal Free Trust, £0.75M).

·        Small animal imaging and electrophysiology  (BHF, £2M).

·        Stanmore Clinical Research Facility (SCRF; UCLB/RNOH, £0.4M).

·        Wellcome Trust Clinical ResearchFacility at UCL/UCLH (£6M).

 

Research Groupings and Achievements

 

(A) Inflammation

(B) Endocrinology

(C) Cardiovascular

(D) Hepatology and gastroenterology 

(E) Respiratory medicine 

(F) Nephro-urology

(G) Musculoskeletal and tissue engineering

(H) Imaging

 

(A) Inflammation 

Research is undertaken at the RFH and Bloomsbury campuses, with strong links to the NHS, including the NSCAG-funded National Amyloidosis Centre.  Long-term funding has been secured by Pepys (MRC Programme Grants since 1979; current £1.8M), Segal (Wellcome Programme Grant since 1982; current £1.9M) and Singer (8 years MRC funding, current £0.5M).

 

A1 Amyloidosis and acute phase proteins

Research of this world-leading group extends from protein structure through molecular, genetic, biochemical, physiological and pathological studies, to clinical diagnostics, patient management and new drug discovery. 

 

Major achievements:

77.Invention of platform technology to design small molecule drugs to deplete pathogenic proteins by a novel pharmacological mechanism. Covered by US and European patents, with compounds in early phase clinical studies targeting serum amyloid P component (Pepys, Nature) and C reactive protein (Pepys, Nature).

78.Critical assessment of the direct pro-inflammatory action of C reactive protein (Pepys, PNAS).

79.Characterisation of the phenotype and response to therapy of systemic amyloidosis (Lachmann, Gillmore, Hawkins, Lancet, NEJM). 

80.Eprosidate (Hawkins, NEJM) and immunosuppression (Hawkins, Blood) to treat amyloidosis.

81.Il-1 inhibition in Muckle-Wells syndrome in adults (Hawkins, NEJM) and children (Hawkins, NEJM).

82.Identification of new genetic causes of amyloidosis (Lachmann, Hawkins, NEJM).

 

A2 Neutrophils, sepsis and resolution of inflammation

Major discoveries in neutrophil biology and Crohns disease. Translational research has led to new concepts in pathogenesis and treatment of human sepsis and resolution of inflammation (Gilroy; new recruit, Wellcome Career Development Fellowship).

 

Major achievements:

83.Potassium channels’ role in neutrophil function casting doubt on the free-radical hypothesis of neutrophil killing (Segal, Nature) and oxidative stress (Segal, Nature).

84.Evidence for immunodeficiency in Crohn’s disease (Segal, Lancet).

85.Epi-lipoxins and other lipid mediators resolve inflammation (Gilroy, PNAS, J Exp Med).

86.Pathogenic role of mitochondrial (Singer, Lancet) and potassium channel (Singer, Lancet) dysfunction in human sepsis.

87.Limited role for pulmonary artery catheters in ITU patient management (Singer, Lancet), treatment of vasoconstrictor resistance in sepsis (Singer, Clapp Lancet), and prevention of MRSA on the ITU (Lancet).

 

(B) Endocrinology 

Withers (MRC Senior Clinical Fellow) and Batterham (MRC Clinician Scientist) were recruited in 2004.  Research grants include a Wellcome Trust Functional Genomic award (£1M) and Strategic award (£1.5M). Interests include gut hormones, obesity and clinical trials in type 2 diabetes.

 

Major achievements:

88.  Peptide YY and pancreatic polypeptide regulates food intake in rodents and humans; peptide YY mediates protein-mediated satiety and energy homeostasis (Batterham, Cell Metabolism, Nature x2, NEJM).

89. Role of insulin signalling pathways in regulation of pancreatic islet and hypothalamic function (Withers, J Clin Invest x2).

90. Role of p110 alpha phosphoinositide-3-OH kinase in growth and metabolism (Withers, Nature).

91.CARDS and PROACTIVE trials (Betteridge, Lancet x2).

 

(C) Cardiovascular 

 

(C1)  Genetic determinants of cardiovascular disease

Areas include genetic variation in lipid, inflammation and coagulation pathways that increase atherosclerosis risk, genetic epidemiology and Mendelian randomisation.  Focus is on gene identification to understand pathogenesis and improve clinical diagnosis in management of inherited causes of sudden death and heart failure. Translational research focuses on FH and HOCM. BHF programme funding includes £1.3M BHF Chair (Humphries), £0.5M (Hingorani) and £1.3M (McKenna). McKenna, Elliot, Syrris and Tuddenham are new recruits.

 

Major achievements:

92.             Interaction between APOE genotype and smoking in coronary disease (Humphries, Lancet).

93.             Pathogenic role of homocysteine in stroke (Hingorani, Lancet).

94.             Bradykinin receptor genotype influence on left ventricular growth (Montgomery, Lancet). 

95.             Disease-causing genes identify ARVC as a disease of cell adhesion (McKenna, Syrris, Human Genetics, Lancet).

96.             Identification of disease-causing genes for: non-sarcomeric HOCM (Elliot, Lancet), restrictive and dilated cardiomyopathy (Elliot, McKenna, J Clin Invest, Lancet).

97.             Determined risk of sudden death in HOCM and incorporated into international guidelines (McKenna, Lancet).

98.             Recognition that majority of young sudden deaths are familial (McKenna, Lancet).

99.             Identification of a spectrum of genetic causes of FH and of the extreme disease risk associated with certain mutations (Humphries J Med Genet).

100.         Genes for hereditary warfarin resistance (Tuddenham, Nature) and haemolytic anaemia secondary to sodium-potassium membrane leaks (Stewart, Nat Genetics).

 

(C2) Acquired cardiovascular disease 

Interests include atherosclerosis, inflammation and vascular disease pulmonary hypertension, VEGF signalling, ischaemic preconditioning, KATP channels, G-protein-gated potassium channels and observational clinical studies and meta-analysis of clinical trial data. Keogh was recruited in 2005. BHF funding £2.8M VallanceC/Leiper.

 

Major achievements:

101.         Infection/inflammation precipitates cardiovascular events in humans (Hingorani, DeanfieldC NEJMLancet, Circulationx2).

102.         Periodontitis causes systemic inflammation and endothelial dysfunction which is modified by treatment (DeanfieldC, NEJM).

103.         Structure of DDAH (Leiper, VallanceC Nat Struct Biol).

104.         DDAH regulates nitric oxide pathways (Leiper, Nat Med).

105.         Clarification of pleiotropic effects of ACE inhibitors in renal disease (MacAllister, Lancet). 

106.         Oligonucleotide-based therapy corrects defects in APO genes (Owen, Nat Biotech).

107.         Endothelial dysfunction determines the risk of pre-eclampsia (Hingorani, Lancet).

108.         Regulation of G-protein coupled potassium channels and KATP channels by protein-protein interactions (Tinker, PNAS x3).

109.         Mechanisms of ischaemic preconditioning and post-conditioning in animals and humans (Yellon, MacAllister, Circulation x5, Circ Res x2, Lancet).

110.         Clinical benefit of biventricular pacing (McKenna, NEJM).

111.         Practice-changing trial of ‘deferasirox’ in iron overload (Porter, Blood).

112.         Risks of venous thrombosis during long-haul travel (Machin, Lancet).

 

(D) Hepatology and gastroenterology 

Eight category A researchers have been recruited in 2001-7 (1 Wellcome Trust, 3 UK Charity, 1 DOH Senior Lecturer and 2 NHS). Rosenberg (Chair of Hepatology) augments programmes combining research on immunity to Hepatitis B & C with therapeutic innovation. Other programmes study liver stem-cells, cell-lines for bio-artificial support, pathophysiology of liver failure, improved therapies for complications of cirrhosis, ischaemia-reperfusion injury and liver transplantation. In gastroenterology, research focuses on bowel physiology and inflammation, led by Forbes, Emmanuel and Day (recruited 2007).

 

Major achievements:

113.         Adoptive transfer of HBcAg-reactive T-cells resolves chronic HBV infection (Naoumov, Gastroenterology).

114.         Delineation of specificity and dynamics of T-cell responses in HBV and untreated HCV infection (Dusheiko, Gastroenterology, Hepatology, J Exp Med).

115.         Role for NK cells in  pathogenesis of HCV  (Rosenberg, Science).

116.         Low penetrance of inherited haemochromatosis, and ferroportin’s role in autosomal dominant haemochromatosis (Walker AP, Lancet, Blood).

117.         Effects of sympathetic nervous system on liver fibrosis and stem cells (Oben, Hepatology).

118.         T3 modulation of liver repair (Hodgson, Hepatology).

119.         Dimethylarginine predicts outcome in alcoholic hepatitis (Mookerjee, Hepatology).

120.         Experimental cirrhosis affects cardiac function via protein nitration (Moore KP, Hepatology).

121.         Medical therapy is as effective as  endoscopic in preventing variceal re-bleeding (Burroughs, Gastroenterology).

122.         Predictive modeling of transplant outcome (Burroughs, Lancet).

123.         Controlled hypothermia restores cerebral autoregulation and reduces raised intracranial pressure in acute liver failure (Jalan, Hepatology, Gastroenterology).

124.         CARD15 mutations cause immunodeficiency in Crohn’s disease (Forbes, Lancet).

125.         Stress modulates visceral pain (Emmanuel, Gastroenterology).

126.         Natural history and neoplastic risks in of ulcerative colitis  (Forbes, Gastroenterology x2).

127.         Liver phenotype of stem cells (Hodgson, Stem Cells).

 

(E) Respiratory medicine 

Long-term funding is through a Wellcome Programme Grant (£1.1M; Laurent).  Wedzicha was recruited in 2005 to lead on COPD research and Lee (recruited 2005) to bridge the translational gap between basic and clinical research in pleural disease. Hurst was recruited in 2007 as DoH Senior Lecturer.  There are research programmes in lung fibrosis, COPD and pneumonia. 

 

Major achievements:

128.         Role of proteinase activated receptor-1 in inflammation and fibrosis in response to lung injury (Laurent, J Clin Invest).

129.         Role of adhesion molecules during the resolution of inflammation (Laurent, J Exp Med).

130.         Clinical trial of surfactant in ARDS (Bellinghan, NEJM).

131.         Classical complement pathway in innate immunity to S. pneumoniae (Brown JS, PNAS). 

132.         Contribution of bacteria and viruses to COPD exacerbations, disease progression and identification of biomarkers of COPD (Wedzicha, Am J Respir Crit Care Med x3).

 

(F) Nephro-urology 

A collaboration between Division of Medicine, and Departments of Physiology and Biochemistry to form the UK’s premier renal physiology group.  Interests include renal genetic diseases and tubular disorders. New recruits are Kleta (2006), Zdebik (HEFCE-funded Lecturer, 2007) and Peppiat (MRC Intermediate Fellow, 2007). 

 

Major achievements:

133.         Cloning and characterization of the epithelial neutral amino acid transporter and discovery of disease causing mutations (Kleta, Nature Genetics).

134.         Cysteamine therapy for nephpathic cystinosis (Kleta, Ann Int Med).

135.         Type III 3-methylglutaconic aciduria caused by mutation in the OPA3 gene (Kleta, Am J Hum Gen).

136.         WNK kinase mutations causing human hypertension (Unwin, Science). 

137.         Modulation of capillary blood flow by pericytes (Peppiatt, Nature).

138.         Transcription factor YB-1, a novel repressor of interstitial collagen α1(I) gene transcription binding (Norman, J Biol Chem).

139.         Outcomes of non-surgical intervention in men with prostatism (Emberton, Brit Med J) and of surgical outcomes in congenital intersex syndromes (Woodhouse, Lancet).

 

(G) Musculoskeletal and tissue engineering 

Marsh (recruited 2005) has interests in osteoporosis, fracture healing and cell-based therapies for musculoskeletal problems.  The Stanmore CRF focuses on regenerative medicine for bone and soft tissue repair. Research in osteoporosis is facilitated at Stanmore, as the hub of a network of fracture units in North London.  Techniques to investigate force transduction at the nanoscale have been developed by McKendry (recruited 2001). Work in this area links closely to UoA3.

 

Major achievements:

140.         Measurements of nano-forces from single cells using atomic force microscopy (McKendry, Horton Nature, Nature Nanotechnology, PNAS).

141.         Use of nano-sensors to detect DNA binding (Pelling, Science, PNAS).

142.         Novel methods of tissue microfabrication (Brown RA, Adv Funct Mat x2).

143.         Spectroscopy for non-invasive measurement of mechanical loading (Birch, J Physiol, Mudera, Tissue Eng).

 

(H) Imaging 

Taylor AM (HEFCE Senior Lecturer from 2007) and Halligan (recruited 2005) brought research programmes in functional, inflammatory and malignant bowel conditions. Advanced imaging techniques include MR perfusion, contrast ultrasonography, MR spectroscopy and radiofrequency tumour ablation. Ell has pioneered the use of Sentinel Lymph Node Biopsy, PET/CT and Ga68 Peptide and Rb82 perfusion PET/CT scanning in the UK and Groves (recruited 2005) has research programmes in angiogenesis and CT perfusion and Hutton (UoA 19) in ultrafast perfusion SPET.

 

Major achievements:

144.         MRI in the management of fistula-in ano (Halligan, Lancet).

145.         Computer-aided detection in colonic disease (Halligan, Gastroenterology).

146.         Sentinel node biopsy in breast cancer management (Ell, J Nat Cancer Inst).

 

Developments Highlighted in RAE2001

Plans outlined in RAE 2001 were to capitalise BHF-funded refurbishment of the Rayne building to strengthen cardiovascular research at UCL.  This has been followed with an award under BHF Cardiovascular Initiative 2, (funding small animal ECHO and MRI), shortlisting by the BHF for a Centre of Excellence Award and the founding of the Cardiovascular Science Institute. The recruitment to the Potter Chair (investment of £2M, 2006) of Kleta from the NIH strengthened nephro-urology and established collaborations with ICH/GOSH. Transfer of renal services from UCLH established RFH as the transplantation centre for UCL. Recruitment of Marsh and Keogh to further the surgical translational agenda; Keogh has recently been appointed as the NHS Medical Director and Deputy Chief Medical Officer. Translational research leading to early drug development has resulted in two large awards (£8M in total) from the Wellcome Trust Seeding Drug Discovery initiative, funding drug development in Amyloidosis (Pepys) and sepsis (Leiper and Singer).    

 

INTERDISCIPLINARY RESEARCH AND COLLABORATIONS

 

Interdisciplinary Research 

Thematic groupings within Institutes and Divisions and cross-cutting themes within the Faculty and University are strong and extensive. Mechanisms that promote such collaborations include shared appointments of category A staff across clusters (5) and Faculties (9), co-ordination of major funding bids by the Faculty Senior management group (membership includes the Directors of the 6 Divisions/Institutes of UoA4) and the BRCs, and cross-faculty undergraduate and postgraduate teaching (including the MBPhD programme). As evidence of interdisciplinarity, 36 Category A researchers from the 3 research clusters are being returned in other UoAs (2, 3, 6, 7, 9, 10, 14, 19, 22, 28, and 42). Some collaborative initiatives with examples of output (in square brackets) are listed below.

 

·        Children Nationwide Children’s Pain Research Centre, involving ICH/GOS Cardiorespiratory Sciences and Neurosciences with Nursing & Allied Health (returned UoA11) and UCL Department of Anatomy and Developmental Biology. [Walker SMO1-4]

·        Clinical Research Facilities at UCLH, Moorfields and GOSH which have underpinned a recent short-listed application to the Wellcome Trust for training programmes in Translational Medicine and Therapeutics (co-ordinated by MacAllister and Khaw). 

·        Congenital uropathies, a programme modelling the childhood conditions in a physiologically appropriate ovine system, for experimental studies.  A collaboration between Nephrourology at ICH (Woolf22), Fetal Medicine at IWH (Peebles18) and Surgery (Fry) [2 joint publications in 2007 not returned].

·        DARC (Detection of Apoptosing Retinal Cells) a collaboration at IO between Cordeiro (glaucoma models), Moss (cell biology), Sillito, Salt & Fitzke (Neuroscience). [Major achievement 24.]

·        Infection and Immunity comprises a strong cross-Faculty collaborative grouping involving Klein (ICH: lead in Infection), Collins (UoA3: lead in Immunology), Population Health Sciences (ICH: Gilbert, Peckham), vaccine development (Weiss) and Gene Therapy (ICH: Thrasher). [Bajaj-ElliottO3].

·        Institute of Healthy Aging, between Biology (Partridge) and Medicine (Withers), and supported by a Wellcome Trust Strategic award of £6M in 2007. [4 papers with Partridge and Withers co-authors since 2004].

·        Lung growth and development involving respiratory physiology (StocksO1,2), epidemiology & biostatistics (DezateuxO1,3,4, WadeO1) physiotherapy (MainO1-3), neurosciences (Kirkham), gene therapy (Hart) and clinical respiratory medicine (AuroraO1, WallisO2) [Major achievements 15, 45].

·        Nanomedicine, through the recently established London Centre for Nanotechnology, a unique operating model that combines the interests of the Departments of Chemistry, Physics, Materials, Medicine, Engineering and Earth Sciences and Medicine (shared appointments of Horton and McKendry. A joint venture with Imperial College. 

·        Obesity research, Childhood Obesity Research Group for ICH (CORGI), a collaboration between epidemiology and biostatistics (ColeC, Power), genetics (Beales), general and adolescent paediatrics (Viner), nutrition (Singhal, LucasC) and Vascular Physiology (DeanfieldC) [Major achievements 4, 43], and the recent UCL/UCLH bid for DOH Bariatric Centre status, between Medicine (Batterham, Withers), Viner and Fiennes (Surgery).

·        Paediatric eye disease, shared posts between IO and ICH (Rahi and Ali) with developments in stem cell and gene therapy (Sowden and Thrasher at ICH, Ali and MacLaren, IO) [Major achievements 35, 65].

 

External Collaborations

Investigators returned in UoA4 have national and international collaborations with world-leading teams. On average, returned staff have 4 national and 7.5 international collaborations that have led to joint grants or publications.  Strategic initiatives for collaborative working at IO include joint appointment of Jose Sahel, Director of a 'sister' vision institute in Paris. This facilitates joint initiatives such as the European Vision Institute. This has led to the European Retinal Research Training Network and the FP6 GENORET programme. ICH has links through the Bloomsbury Centre for Tropical Medicine, London CF Collaboration and the NSCAG UL research network (pulmonary hypertension and paediatric rheumatology). The European Amyloidosis Collaboration (EURAMY) links UCL/RFH with centres in Europe (£2M). EU-funded initiatives exist in pulmonary hypertension, pulmonary fibrosis, inherited renal disease.

 

INTERACTIONS WITH THE NHS

 

Introduction

Throughout UoA4, UCL Institutes and Divisions integrate research with their partner NHS Trusts, through united strategic planning, shared infrastructure and close physical proximity. There is cross-representation on recruitment panels for academic or consultant staff and there have been 27 joint appointments since 2001. University staff are embedded within NHS structures. Category A academics in Experimental Medicine include the Medical Director at the RFH, and two (of 12) Clinical Directors at UCLH.  At IO and ICH, the Institute Directors are non-executive Directors on the respective Trust Boards. The UK NHS National Amyloidosis Centre at Royal Free Hospital (Pepys and Hawkins), is currently funded at ~£2.5M per year by the DoH through NSCAG and delivery of the national referral service underpins its world leading research. Category C staff (highlighted throughout by a superscript suffix ‘C’) and non-returned research NHS colleagues form a key component of our joint research effort.

 

Biomedical Research Centres

Eleven Biomedical Research Centres (BRCs) were established by the DoH in 2006 and three of these are involved with this UoA. There are Specialist BRCs at IO (£13.5M) and ICH (£35M) and both IWH and Experimental Medicine are important components of the UCLH/UCL CBRC (£80M). Five Category A staff from Experimental Medicine lead themes in the CBRC and its Director also directs IWH.  At IO, three of the five theme leaders and the BRC Director are Category A university staff while at ICH all 3 theme leaders and the BMRC Director are Category A. The BRCs offer opportunities to catalyse translational medicine and will play a key role in the organisation of an integrated programme of biomedical research across UCL.

 

Research and Development Office Restructuring

R+D support is integrated between NHS and University partners at different sites and across the FBS. There is a joint R+D office for UCL and UCLH/RFH directed by Jacobs (Director IWH), with a team to support governance and trial management, and  joint offices support activities at ICH/GOSH and IO/MEH, with convergence of procedures at the 3 sites.

 

Department of Health

The DoH has provided over £11M funding and this has included support for a London Genetics Knowledge Park (Scambler PJ; £2.8M), gene therapy (Ali, Gaspar, Hart; £1.7M) and HIV-related research (Cortina, Dezateux, Peckham; £1M). 

 

CAPACITY BUILDING

Introduction

The components of UoA4 are outstanding environments for the training of post-doctoral researchers and postgraduate students. The combination of internationally competitive, multi-disciplinary research groups with a strong translational perspective and well-equipped laboratories is compelling. Research assistants and students are exposed to the skills, technologies and resources of the highest possible relevance to the current and emerging needs of the UK biomedical research. Currently there are 215 PhD and 66 MD students in training. 

 

Student recruitment and selection

Through the Graduate School we advertise opportunities for post-graduate education in Biomedicine. Recruitment rates have been relatively constant (~120 per annum; see RA3b). There are five BSc, one MRes and 13 MSc courses with opportunities to encourage medical students to consider research early in their training.  Institutionally-funded PhD projects are submitted to a central committee and peer-reviewed. Projects/supervisors are advertised and students appointed competitively.  Students are reviewed, at 6 months and then yearly.  Each student is interviewed by the Postgraduate Tutor or a Postgraduate Advisor with responsibility for monitoring progress.  MPhil to PhD upgrade is carried out between 12 and 20 months after registration and involves preparation of a written report, an oral presentation and a mini-viva examination.

 

Full-time students are supported by studentships from MRC, BBSRC, Wellcome Trust, BHF, other medical charities and internal charitable funds. The number of research council funded students is increasing (20% in 2007) and Wellcome Trust and BHF awards dominate in the UK charity sector. Dedicated 4 year PhD programmes are of increasing importance and include: (i) MRC Laboratory for Molecular Cell Biology, (ii) Wellcome Trust Neuroscience, (iii) Wellcome Trust Stem Cell & Developmental Biology, (iv) MRC Doctoral Training Account in Biomedicine. Any external studentship awarded at less than the MRC rate is supplemented by internal funds to prevent student hardship.  Part-time non-clinical students (primarily research assistants employed on research grants) are encouraged to undertake PhD training for career development. Their part-time PhD fees (0.5 FTE) are generally met 50% by the Institute and 50% by the student (listed as studentships which are 50% Institutional funded, 50% other–self-funded).

 

Generic skills training 

This is required for all research students and includes in-house courses in research methods (including animal procedures), training in health and safety/risk assessment, computing and data handling/statistics. In addition, there is access to a range of courses offered by UCL Graduate School.  All registered students are expected to undertake at least 2 weeks of generic skills training per annum during their higher degree, with activity logged and audited electronically. It allows students, in consultation with supervisors, to carry out a self-audit of relevant skills, to prioritise the acquisition of skills in particular years of study, and to maintain a comprehensive account of research training and experience.

 

Student prizes, publications and destination

Completion rates range from 70 - 80% across the UoA. Where data are available, between 2001-2007, 457 postgraduate students published 1298 papers of original data and review articles with their supervisors. Of a sample of 313 former students, 15 have become academics (including 10 being returned to UoA4 (Bainbridge, Foster, Gillmore, Hausenloy, Lachmann, Mookerjee, Wildmann, Qasim, Osrin) and two to UoA3). 27% of students took up post-doctoral positions, 6% went to industry and 42% returned to clinical work. Thirty one research students won 37 national and international research prizes:

 

Career paths for PhD-trained staff

Non-clinical PhD graduates typically move on to grant-funded post-doctoral support.  Clinical PhD or MD graduates complete specialist medical training at the end of the higher degree. We attach great importance to supporting non-clinical and clinical early career staff and several schemes are in operation, for staff of varying seniority, to encourage post-doctoral research training. We have had substantial success in DoH Clinical Lectureships and Intermediate Fellowships (35 including 13 from the Wellcome Trust).  At a senior level we have received 13 HEFCE Clinical Senior Lectureships and 31 Category A staff are currently funded on Fellowships. We have moved 36 staff into definitive or committed HEFCE-funded positions. 

 

 

STRATEGY 2008-2013

 

Our primary goal is to continue to generate the highest possible quality research for the ultimate benefit of patients across the wide range of disciplines in this return. Given the depth and breadth of basic science at UCL and the specialist expertise in ophthalmology, medicine, surgery, child health, musculoskeletal disorders and hearing, we are in an ideal position to deliver the translational research mission envisaged by Cooksey and supported in an increasingly focused way by the MRC and UK charities.  Central to the delivery of this mission is extended collaboration between groups, recognising the substantial opportunities for synergy between discrete medical areas, translational programmes and investigators in fundamental biological sciences, computing and engineering. Several recent initiatives to facilitate joint working are described in “Interdisciplinary Research and Collaborations”. At the macro level, the new School of Biomedical and Life Sciences has a pivotal role to exploit the full potential of co-location with the MRC’s National Institute for Medical Research in Bloomsbury. Cross-UCL Centres, such as the UCL Centre for Stem Cell Research (Stern) and UCL Institute for Healthy Ageing (Partridge) and UCL Global Health (Costello), UCL Regenerative Medicine (Mason), cross-cutting thematic developments such as Vision@UCL (Johnston) and specialist facilities such as the London Centre for Nanotechnology will also facilitate innovation, collaboration and delivery of therapeutic and diagnostic outcomes.  Within FBS, Technology Platform Groups are currently in advanced stages of planning for cross-faculty developments in proteomics, drug development and medicinal chemistry, genomics, transgenics and animal imaging.

 

The Faculty’s finances enable the Dean to support areas of strategic importance. Institute and Division Directors have delegated budgetary responsibility and influence strategy locally. Benevolent funding is central to advancing new areas of activity and we work closely with the new Head of the UCL Development Office, fundraisers and charities to match research strategy with unmet need.

 

Links with NHS Trusts

We will continue to build on the existing partnerships between Institutes and Divisions and NHS Trusts including the 3 BRCs to create a rich, integrated biomedical community of world-class stature, comparable to the Harvard Medical Area. We intend to implement Academic Research Medical Centres, as outlined in Darzi’s Framework for Action for London Health, in a configuration that will reflect local needs and strengthen links between academia and healthcare. In NHS R+D, the joint research office (UCL Biomedicine, UCLH and RFH Trusts) will facilitate efficient implementation of GCP, the Research Governance Framework and provisions of the Human Tissue Act. The CRFs at UCL/UCLH, IO/MEH and ICH/GOSH will be catalysts for translational research.  

 

External academic links

Strengthening links within London is a priority. The School of Pharmacy shares a Centre for Paediatric Pharmacy with ICH/GOSH to enhance child-centred medicine formulation. A joint Professorial appointment between the School of Pharmacy and the IO/MEH SBRC is in planning stages, to enable development of novel generic approaches in drug delivery to the eye. Other examples include the London Centre for Nanotechnology and the UCL Technology Platform Group in Genomics, with links to London School of Hygiene and Tropical medicine.  A broader initiative is the Global Medical Excellence Cluster (GMEC) in the South East: UCL is working with Imperial College, KCL, Oxford and Cambridge, to create a GMEC to compete with those elsewhere in the world. 

 

Capacity Building

Training the next generation of biomedical and clinician scientists is a priority. The BRC have educational components for Translational Medicine and will be used to increase taught post-graduate student numbers by developing attractive modular courses based in the FLS and FBS. A priority is the establishment of further 4-year PhD programmes (such as Stem Cell and Developmental Biology). In partnership with GSK we have recently been short-listed for a Wellcome Trust award in Translational Medicine and Therapeutics for MSc, MBPhD and Clinical PhD studentships. We will prioritise a 4-year programme dedicated to eye disease research, a current unmet need in the UK. 

 

Strategy by Overarching theme

 

GENETICS AND GENE THERAPY

Further development of research excellence in genetics has been prioritised as a cross-cutting UCL theme with a new UCL-wide Genetics Initiative, led by Humphries. This will build upon and integrate the existing strengths and develop capacity in Biostatistics, Genetic Epidemiology, Pharmacogenomics, and Genome Informatics, areas of emerging strength at UCL. Infrastructure to support this effort (e.g. high throughput sequencing/genotyping platforms) will be developed in collaboration with new recruit (Hardy UoA9). This will extend the scope of research and provide new opportunities for collaboration, both within UCL and with external partners. We will expand the highly successful programme of gene therapy for immunodeficiency disease and retinal disorders, with a translational research emphasis on new diseases (e.g. bone marrow transplantation, skin disease, metabolic disease), while continuing to extend the underlying science base.  This activity is supported at ICH by 2006/07 awards of £315K (MRC) and £310K (DoH) to Gaspar and £764k (MRC) to Thrasher. Our extensive experience of GMP and regulatory procedures will facilitate rapid expansion into new areas.  We are developing a vector core facility for the large-scale generation of clinical grade virus.

 

REGENERATIVE MEDICINE AND STEM CELLS

Existing facilities at IO for human stem cell transplantation will be expanded as existing programmes for the treatment of retinal degeneration and other conditions move towards clinical trials. This activity is driven by awards in 2007 of £4M (Coffey), £0.5M from MRC (Ali) and £0.7M from MRC (MacLaren). The GMP-compliant cell culture facility, being built at Stanmore, in partnership with the Korean company Cellontech, will provide a translational pipeline of cell-based musculoskeletal therapies, with the Stanmore CRF coordinating the associated clinical trials. Strong links will be formed with the recently established MRC Centre for Neuromuscular Disease (Koltzenburg, Hanna - UoA9, with Newcastle University) and the incoming Dubowitz Neuromuscular Centre (Muntoni to be recruited to ICH in late 2007). Using stem-cell expertise at IO, a spinal repair programme (Raisman) will be developed.  Proof of principle studies will extend to new areas, including use of novel amniotic fluid-derived stem cells in gut tissue engineering (De Coppi) and identification of endogenous cardiac stem cells (Riley). The move to clinical trials and health service provision will ensure the earliest possible delivery of solutions to patients.  A major goal is the development of structures capable of delivering ‘biologicals’ to large numbers of patients.  A new cross-UCL initiative in regenerative medicine (Mason, UoA26) will focus on this challenge.

 

NEUROCOGNITION

The collaborative network between IWH and ICH addressing cognitive sequelae of neonatal events (supported by £792K MRC programme to Vargha-Khadem, Wyatt, Deanfield, Gadian) will expand as head-cooling protocols are developed for clinical implementation, and prospective neuroimaging and neuropsychological measures of long-term neurocognitive outcomes. Expansion of visual and auditory neuroscience (e.g. Daudet, BBSRC £430K 2007) will feed into translational programmes designed to optimise residual function and use of prosthetics for vision and hearing impairment. This expansion will be further supported by recent £1M MRC Strategic Award (Carandini). 

 

IMAGING

In Nuclear Medicine, recruitment to the Esperanca Chair of Molecular Imaging will occur in 2008, with a remit to link between clinical imaging and chemical biology (Caddick; UoA 18) with the development of new imaging probes.  The UCL Centre for Biomedical Imaging, (part-funded by BHF; Lythgoe) has been established to provide structural CT, MRI, SPET and PET specifically for use in small animal disease models, and will link non-clinical with clinical imaging. Custom designed laboratories co-locate magnets and scanners next to animal holding rooms and operating theatres. Imaging of cell death in the retina will be supported by a £2m commercial partnership and a component of ongoing support from Foundation Fighting Blindness (Fitzke £0.8M 2006), while the 2006 £8.4M capital investment by BHF/GOSH Trustees in cardiac imaging at ICH/GOSH is supported by a new £387k (DoH) award to Taylor AM

 

LIFELONG HEALTH

At the basic science level, UoA4 life-course research in this area will be closely linked with the Institute of Healthy Aging and underpinned by £1.5M Wellcome funding (Withers). In more applied work, novel interventions for health promotion will be developed, e.g. based on a patented milk formula to match infant growth to that of breast-fed babies and minimise later cardiovascular risk (LucasC with ongoing 2007 MRC support to Singhal of £1.3M) and to implement low-cost measures (e.g. local women’s groups) that enhance perinatal care and cut neonatal mortality in resource-poor countries (Costello; Department for International Development, £2.5M, Osrin; Wellcome Trust Fellowship, £0.6M).  Research in child health policy development will be expanded with close links to health economics and social sciences (Law). Epidemiological approaches will be enhanced by 2007 award of £1.7M for MRC Centre (Dezateux). Across UoA4 there will be growing emphasis on age-related disorders, with planned recruitment to a Chair of Healthy Ageing in 2008.

 

STAFFING POLICIES

 

Research assistants/technicians

Contract research staff usually belong to a single multidisciplinary research team, although inter-team working is strongly encouraged. Research staff are transferred to open-ended contracts upon completion of the probationary period, and are given priority for redeployment within UCL at the end of a grant funding period, if renewal funding is not available within the team. The Study Assistance Scheme helps research assistants register for a higher degree (with the approval of the supervisor). Postdoctoral researchers are appropriately encouraged to apply for external funding (e.g. MRC New Investigator Grants, MRC/Wellcome Trust Career Development Fellowships). Careers advice is provided by a UCL Careers Service and informally by our network of PIs.

 

Mentorship of junior faculty (e.g. Fellowship holders).  

Each Division/Institute has a formal mentoring scheme for all staff. There are schemes to support junior faculty members including internal pump-priming research funds (Science Development Initiative, the Child Health Research Appeal Trust (ICH) and the Clinical Research Development Committee (UCL/UCH)). Undergraduate teaching is managed to facilitate a culture of research, and to improve recruitment of research students without detracting from the research agenda.

 

Progress of Lecturers and Senior Lecturers 

This is considered annually through appraisal and formally at a Probationary Progress Review at the end of year 3 for Lecturers on initial 4-year contracts, and at the end of year 4 for Senior Lecturers on initial 5-year contracts. Senior promotions are managed through an annual, UCL-wide process led by the Provost; there have been 11, 22 and 27 academics promoted to Senior Lecturer, Reader and Professor respectively.

 

Clinical Academics (including Category C staff)

We recognise the particular challenges facing university and Trust staff combining clinical duties with research and teaching. Physical and intellectual integration is a high priority and junior clinician scientists have dual mentoring, this leading into joint appraisal by senior Trust and university staff following appointment to faculty positions. Care is taken not to overburden research staff with teaching.

 

Senior staff have left to take Chairs at other academic institutions (Baxter, Bertoletti, Connelly, Cree, Erusalimsky, Groves, Marber, Ono) and two have moved to senior positions in the pharmaceutical industry (VallanceC and NauomovC) although their academic research remains linked to UCL.  Departures, and retirements of senior staff, have been managed where strategically appropriate by recruitments in similar or aligned areas (eg Rosenberg, Hausenloy, Clark, Withers to replace Nauomov, Baxter, Connelly and Erusalimsky). Cree continues to collaborate over ocular oncology and following Ono’s departure we are building links in immunology with the main campus.

 

COMMERCIAL LINKS

 

From 2001-2007 we received over £8.6m in income from UK industry, commerce and public corporations and the vast majority of this supported investigator led research.

 

UCL Business (UCLB) provides a service for technology transfer and IP protection and development. ICH/GOSH has a joint Technology Transfer Management Group. Commercialisation opportunities and patent issues are managed by the Joint Strategy Board at IO/MEH. A pro-active approach to commercial partnering has included IP audits and greater interaction with the biopharmaceutical industry. 

 

·        ARK Therapeutics, publicly quoted in 2004, one of the most successful biotech companies in the UK.

·        Evexar Medical Ltd, medical device company for hernia and vascular surgery.

·        Genex, initiated at ICH in 2005 based on patents covering non-viral gene therapy using integrin/lipid vectors (Hart). Funding from the Bloomsbury Bioseed Fund (£250K) and the Wellcome Trust (£385K Translation Award).

·        Industry-funded studentships, 5 in Experimental Medicine.

·        Ophthaltec, works with IO to develop new compounds for the treatment of eye disease.

·        Orphan drugs, developed by ICH as part of long term collaborations between ICH and industry.

·        Patents: 49 patents since 2001, from novel magnetic contrast agents (Gadian) and stem cell lines (Khaw) to a new infant formulae for optimal neonatal growth (LucasC).

·        Pentraxin Therapeutics Ltd, which holds all IP related to amyloid and acute phase proteins.

·        Stanmore Implants Worldwide Ltd, world-leader in complex limb reconstructions; active in 20 countries.

 

 

INDICATORS OF ESTEEM SINCE 2001

 

As elsewhere, ECRs are highlighted by underlining.

 

FRS:              Kemp 2004

FRSE:            Bhattacharya 2006

FMedSci:      16 returned staff with FMed Sci awarded since 2001

 

Numbers of Staff Returned with Membership of Funding Committees

Diabetes UK                                                 1

BHF                                                                3

British Retinitis Pigmentosa Society         2

Fight for Sight                                               3

MRC                                                               8

SPARKS                                                       3 

Wellcome Trust                                            8 

Others                                                            8

 

Prizes

Ali; Sir Jules Thorn Award, GSK award, Fincham Medal, Foulkes Medal (Academy)

Bainbridge: Academy of Medical Sciences Award for Ophthalmology 2003

Batterham: G.J. Mendel Award to Top British Young Researcher 2005; European Association for Study of Obesity, Young Investigator Award 2004

Bhattacharya: Chair of Excellence, Paris 2006

Bird; Helen Keller Prize

Cordeiro: Lewis Rudin Award 2005 

Ell: WNA Distinguished Award for Peaceful Use of Nuclear Energy 2006, Gold Medal – University of Ghent 2004

Fitzharris: Charles & Yule Brogue Fellowship 2002

Gilroy: Bayer Prize 2005; BPS Novartis Prize 2006 

Hingorani: BPS Clinical Pharmacology Prize 2006

Homer: Medical Research Society Young Investigator Award 2007

Khaw: ARVO / Pfizer Translational Award 2005, Alcon Prize

Laurent: Annual European Respiratory Societies Presidential Award 2003

LucasC: James Spence Medal, RCPaed, 2005

Martin: Finalist Descartes Prize 2004

MacLaren: Royal College of Surgeons Edinburgh King James IV Professor

McKenna: Arrigo Recordati Prize 2005

Montgomery: ESCI award for Excellence in Clinical Science 2002

Osrin: Royal College of Paediatrics and Child Health, Plenary Lecturer, 2004

Peckham: James Spence Medal, RCPaed, 2003

Pepys; Royal Society GSK Prize, 2007 

Rosenthal: Edgar Gentilli Prize (x2) of RCOG

Rubin: Garland Clay Award from American Academy of Optometry, Edgridge Green Medal, RCOpth

Ruhrberg: Werner-Risau Prize for outstanding contributions to endothelial cell biology

Taylor SA: Roentgen Professorship, Royal College of Radiologists

Thrasher: Descartes Prize for Research & Science 2006

Vargha-Khadem: Jean-Louis Signoret Prize of American Academy of Neurology, 2006

Widschwendter: Hochst Research Award 2002, Ernst Brandl Award 2003

Williams RS: Distinguished Service Award, British Association for the Study of the Liver, 2003

Withers: Linacre Fellowship, RCPhys, 2001

 

Contribution to major advisory bodies

Baldeweg: British Assoc for Cognitive Neuroscience (Chair)

Copp: Academy Medical Sciences Sectional Committee 2

Cross: Epilepsy Research Foundation Trustees (Chair)

David: RCOG Guidelines Committee

Elliott: Council of British Congenital Cardiac Association

Fine: Non-Executive Director of NICE

Halligan: Member, UoA4 Panel; British Society of Gastrointestinal and Abdominal Radiology (Chair)

Hart: American Society of Gene Therapy Non-Viral Committee

Jacobs: Health of Women Trustee, Ovacome Trustee, Eve Appeal Medical Director, European Society of Gynaecological Oncology (President)

Law: Public Health Advisory Committee of NICE (Chair)

Luxon: Royal College of Physicians Council, International Assoc of Physicians in Audiology (President Elect)

Martin: European Society of Cardiology Task Force on Stem Cells and Repair of the Heart (Chair), European Society of Cardiology (Vice President)

Mythen: Council of Intensive Care Society of GB/Ireland

Peckham: Leader of Science Coordination Committee, Foresight Project (Infectious Disease)

Pepys: Royal Society Sectional Committee 10; Royal Society Council; Academy of Medical Sciences Council

Thrasher: Board of Directors of American Society of Gene Therapy

Tomkins: Board of Trustees, UNICEF, UK

VallanceC: Chair, UoA1 Panel

Wedzicha: DoH COPD NSF Committee and Acute Management Sub-committee (Chair)

Wyatt: RCPCH Ethics Advisory Committee, Council of Medical Defence Union

 

Number of Staff on Journal Editorial Boards / Section Editors

31

 

Selected Keynote addresses/named Lectures

Ell: The Henry Wagner Memorial Lecture 2003, The AΩA Honor Professorial Lecture 2003 and others

Humphries: 2004 Plenary Lecture at European Atherosclerosis Society, 2005 Royal College of Pathologists, Freddy Flynn Lecture July 2004, 2006, Plenary Lecture at International Atherosclerosis Society

Khaw: Duke Elder Lecture and Medal 2003, Dame Ida Mann Lecture and Medal 2004, New York Academy of Ophthalmology Achievement Award 2005, Lang Lecture and Medal RSM 2006, A-Star Professorship Singapore University and others

Moore AT: Franceschetti Medal and Lecture International Society of Genetic Eye Disease 2003 and others

Pepys: Heberden Medallist, British Society for Rheumatology, 2002. State of the Art Lecturer, American Society of Nephrology, 2003. Harveian Orator, Royal College of Physicians, 2007

Williams RS: FitzPatrick Lecture, Royal College of Physicians 2006

Withers: Linacre Fellowship of the Royal College of Physicians 2001