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Cancer Studies (Research Division)
|MPhil/PhD
|Part Time, Full Time
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Staff interests associated with the research programme and its research groups
Monitoring of cancer occurrence, to include the analysis of different aspects of cancer prevention,diagnosis, prognostication, treatment and care. Cancer services research investigates variation in the provision of cancer services and related outcomes between different geographical areas or over time. Assessment of how local and national targets for cancer services provision are met, providing information to the planning of cancer services.
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Interests:
Inequalities in cancer occurrence and survival. The influence of policy initiatives on patterns of care, treatment, and patient experience.Determinates of patient experience and place of death. The epidemiology of less common cancers. Using clinical data sets and routine data set links to understand clinical care. The potential use of patient survey data for quality improvement. Novel methods of presenting routine data (maps, funnel charts and control charts) in quality improvement.
Tel:
020 7378 7688
Email:
Website:
Interests:
Cancer epidemiology and analysis of cancer care and outcomes at the population level.
Tel:
020 7188 9286
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Interests:
Professor Holmberg's research group is currently working on clinical aspects of breast cancer (e.g. long term outcome after new ipsi- or contralateral breast events), on aetiology of prostate cancer with special emphasis on the role of the metabolic syndrome and on translational research in lung cancer (e.g. the characteristics of long term survivors of lung cancer). The group works closely with Thames Cancer Registry on national and international comparisons of cancer survival. Virtually all the studies are undertaken in a network with Scandinavian and American researchers. The research group also has a strong interest in cancer screening, and in developing new concepts of survival analyses that better accommodate the role of competing risks in an ageing population burdened with cancer. There are plans to further develop programs to aid clinical decision-making related to tumour markers.
Tel:
020 7188 9286
Email:
Website:
Tel:
+44 (0)20 7188 7904
Email:
Website:
Cancer cell biology, gene target, biomarker discovery and cancer cell imaging are the main areas of interest. Also small molecule and mini-gene therapeutic approaches in breast cancer cells to inhibit chemotaxis. Research includes development of fluorescence life time imaging microscopy (FLIM) for in vivo imaging, as well as imaging of patient samples.
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The laboratory is interested in how cancer cells are able to dissociate from the primary tumour, invade the surrounding tissue and subsequently metastasise to distal sites. Tissue invasion and migration require cancer cells to reorganise their actin cytoskeleton as well as adhere to and degrade the surrounding extracellular matrix. It is well established that cytoskeletal rearrangement, cell adhesion formation and turnover is regulated by Rho GTPases, Rho, Rac and Cdc42. PAKs are serine/threonine kinases that operate downstream of Rho GTPases to control cytoskeletal organisation and substratum adhesion. The PAK family can be sub-divided into two groups; Group 1 PAKs (1-3) and Group 2 PAKs (4-6) based on sequence homology and members of both groups are activated by growth factor signalling pathways. We use live cell imaging, biochemical and molecular approaches to investigate the role of PAK family kinases in cancer cell migration, adhesion and invasion.
Tel:
020 7848 8769
Email:
Website:
Interests:
Cancer, kinase signalling pathways, PSKs, apoptosis, cytoskeleton, cell shape, migration, cell cycle and prostate
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Email:
Interests:
In our studies to understand how cancer cells divide and metastasise, we have identified a novel family of protein kinases which we have called PSKs/TAOKs. PSKs bind to microtubules directly and regulate their dynamics and organisation and their functions are essential for cancer cells to proliferate. Current projects are employing a wide range of different cell and molecular biology techniques to investigate how PSKs act mechanistically to perform their functions and also to evaluate these proteins as suitable therapeutic targets for drug inhbition and the treatment of cancer.
Tel:
020 7848 8302
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Website:
Interests:
Interests are broadly based in defining signal transduction pathways, their action, functional status, prognostic and therapeutic potential in cancer. The research is particularly focused around the protein kinase C superfamily and growth factor receptor action and pathophysiology.
As membrane and protein complex associated protein kinases, these signal transducers operate in spatially restricted compartments and serve highly localised roles in controlling signal outputs. Recent studies have focused on spatial and dynamic aspects of signalling propagated through and/or influenced by these kinases, including the conformational nature of nucleotide binding (and the influence of interventions at this binding site), single molecule analysis of growth factor receptor behaviour, controls acting on the HGF-cMet growth factor signalling pathway, integrin actions in migration, the localisation of signals during migration and general roles in proliferation and survival.
Application of molecular insights derived from the studies on these kinases and the methods developed for this purpose are significant current objectives. This includes drug development activities, biomarker discovery and biomarker methodologies.
As membrane and protein complex associated protein kinases, these signal transducers operate in spatially restricted compartments and serve highly localised roles in controlling signal outputs. Recent studies have focused on spatial and dynamic aspects of signalling propagated through and/or influenced by these kinases, including the conformational nature of nucleotide binding (and the influence of interventions at this binding site), single molecule analysis of growth factor receptor behaviour, controls acting on the HGF-cMet growth factor signalling pathway, integrin actions in migration, the localisation of signals during migration and general roles in proliferation and survival.
Application of molecular insights derived from the studies on these kinases and the methods developed for this purpose are significant current objectives. This includes drug development activities, biomarker discovery and biomarker methodologies.
Tel:
020 7848 6835
Email:
Website:
Interests:
The Ameer-Beg group aims to further our understanding of cell signalling dynamics and control. We develop optical instrumentation to address fundamental biological questions regarding the dynamic interaction of protein partners within the cellular membrane. The group’s interests range from high-resolution imaging of tumours using multiphoton fluorescence lifetime imaging to the interrogation of single-molecules within cellular membranes.
Our group is intimately involved in an initiative to develop ‘optical proteomic technology for in situ analysis of protein interaction networks’. Involving a number of research groups within the college aims to develop high-throughput/content optical screening approaches for cell based assays of protein-protein interactions. As part of a strategic programme of research within the biophysics community at KCL, we have established a novel high-throughput fluorescence lifetime/anisotropy imaging/FRET-based assay that identifies perturbations in intramolecular interactions using molecular librariesin mammalian cells.
The Cell Imaging and Biodynamics group is part of the joint UCL/KCL Comprehensive Imaging Centre where we will develop high-resolution multiphoton FLIM for measurement of FRET within thick biological specimens. We aredeveloping adaptive optics techniques to improve multiphoton imaging at depth within biological specimens.
The group is currently developing novel single-molecule imaging methods to observe protein-protein interactions at the cell membrane using a combination of super-resolution techniques and fluorescence lifetime spectroscopy as part of a collaboration seeking to unravel the dynamics of complex signalling networks.
Our group is intimately involved in an initiative to develop ‘optical proteomic technology for in situ analysis of protein interaction networks’. Involving a number of research groups within the college aims to develop high-throughput/content optical screening approaches for cell based assays of protein-protein interactions. As part of a strategic programme of research within the biophysics community at KCL, we have established a novel high-throughput fluorescence lifetime/anisotropy imaging/FRET-based assay that identifies perturbations in intramolecular interactions using molecular librariesin mammalian cells.
The Cell Imaging and Biodynamics group is part of the joint UCL/KCL Comprehensive Imaging Centre where we will develop high-resolution multiphoton FLIM for measurement of FRET within thick biological specimens. We aredeveloping adaptive optics techniques to improve multiphoton imaging at depth within biological specimens.
The group is currently developing novel single-molecule imaging methods to observe protein-protein interactions at the cell membrane using a combination of super-resolution techniques and fluorescence lifetime spectroscopy as part of a collaboration seeking to unravel the dynamics of complex signalling networks.
Tel:
020 7848 6558
Email:
Website:
Interests:
Cancer Cell Motility and Imaging
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Research covers mechanisms that regulate normal haemopoiesis and the causes of leukaemia, bone marrow failure disorders (including myelodysplastic syndromes and aplastic anaemia), myeloma and other haematological malignancies; developmental research of existing immunotherapy and gene therapy strategies; clinical research which involves extending the role of haemopoietic stem cell transplantation and molecular and cell biological analyses of the action of drugs in clinical trials and of new compounds.
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I am interested in the immunology of and immunosuppression in B-CLL. I am currently looking at the involvement of the microenvironment in in B-CLL and specifically the effect of T cells and endothelial cells on the malignant clone. i am currently trying to create a basic model to study this invitro. My work involves and lots of tissue culture, flow cytometry, proliferation assays and anaysis of cytokines. I am moving onto immunofluorescence staining of Lymph nodes using multiple markers to study this in-vivo.
Tel:
020 7848 5803
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Leukaemia is a clonal disease initiated from a very small number of pre-leukaemic stem cells (pre-LSCs) carrying the initiating genetic events, which subsequently convert to full blown LSCs by acquiring further mutations necessary for the overt diseases such as acute myeloid leukaemia (AML). Emerging evidence indicates that pathways critical for regulation of normal stem cells are frequently hijacked or mutated in LSCs. My group is interested in understanding the molecular and cellular mechanisms underlying the oncogenic conversion of normal cells into AML stem cells.
Please visit Prof. So’s website (www.ericso.org) for further details.
Please visit Prof. So’s website (www.ericso.org) for further details.
Tel:
78485888
Email:
Website:
Interests:
Gene therapy-mediated immune rejection of cancer; cellular differentiation; molecular genetic analysis.
Tel:
+44(0)2078485902
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Interests:
(Head of Division) Molecular evolution and treatment of myelodysplastic syndromes (preleukaemia); immune gene therapy for leukaemia; bone marrow transplantation for myeloid malignancies.
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Interests:
Tumour specific induction of apoptosis
Autologous bone marrow transplantation is an alternative therapeutic option for patients suffering from haematological malignancies lacking an HLA compatible donor. However, disease relapse remains a primary cause of death due in part to autograft contamination with clonogenic tumour cells. The multiple purging strategies developed to date have proven ineffective in eradicating the tumour cells from the autologous haemopoeitic stem cell grafts. Pharmacological and immunological approaches to eliminate the leukaemic cells from autografts are often toxic to the normal haematopoietic progenitors, limiting the clinical utility. Reduction of the tumour burden by positive/ negative selection procedures require the presence of differentially expressed membrane antigens on either the tumour cells or the normal haematopoietic progenitors and stem cells which is not generally the case in haematological malignancies. In order to improve the efficacy of cell purging we are studying a chicken anemia virus (CAV) derived protein called Apoptin. Apoptin is a protein which has been shown to induce apoptosis in a variety of human malignant and transformed cells, but not in normal cells
MicroRNA target discover
MicroRNAs(miRNAs) are a novel class of small RNA molecules that can regulate the expression of many genes.They have been shown to be involved in many fundamental processes such as differentiation, proliferation, apoptosis and play a role in cancer. Several microRNAs can act as either oncogenes or tumour suppressor genes. It is currently thought that in humans miRNAs acts mainly by mediating specific translational inhibition and to a lesser extent degradation of mRNA targets.
The role and targets of most miRNAs in humans are largely unknown. Computational identification of miRNAs targets using various algorithms provide some insight into the miRNAs targets,however the drawbacks of these predictions are that they all have a substantial false positive rate and may be biased as they are mostly based on the few known miRNA:target gene interactions.The need for a functional assay to identify the miRNA target is the need of the hour.
We have developed a novel functional assay to enable identification of functional miRNA targets. In a pilot project we used mir130a and its verified target v-maf musculoaponeurotic fibrosarcoma oncogene homolog B(MAFB)as a proof of concept,this identified a further panel of mir130a targets none of which were identified as potential targets of mir130a by the available target pridiction programmes.
Autologous bone marrow transplantation is an alternative therapeutic option for patients suffering from haematological malignancies lacking an HLA compatible donor. However, disease relapse remains a primary cause of death due in part to autograft contamination with clonogenic tumour cells. The multiple purging strategies developed to date have proven ineffective in eradicating the tumour cells from the autologous haemopoeitic stem cell grafts. Pharmacological and immunological approaches to eliminate the leukaemic cells from autografts are often toxic to the normal haematopoietic progenitors, limiting the clinical utility. Reduction of the tumour burden by positive/ negative selection procedures require the presence of differentially expressed membrane antigens on either the tumour cells or the normal haematopoietic progenitors and stem cells which is not generally the case in haematological malignancies. In order to improve the efficacy of cell purging we are studying a chicken anemia virus (CAV) derived protein called Apoptin. Apoptin is a protein which has been shown to induce apoptosis in a variety of human malignant and transformed cells, but not in normal cells
MicroRNA target discover
MicroRNAs(miRNAs) are a novel class of small RNA molecules that can regulate the expression of many genes.They have been shown to be involved in many fundamental processes such as differentiation, proliferation, apoptosis and play a role in cancer. Several microRNAs can act as either oncogenes or tumour suppressor genes. It is currently thought that in humans miRNAs acts mainly by mediating specific translational inhibition and to a lesser extent degradation of mRNA targets.
The role and targets of most miRNAs in humans are largely unknown. Computational identification of miRNAs targets using various algorithms provide some insight into the miRNAs targets,however the drawbacks of these predictions are that they all have a substantial false positive rate and may be biased as they are mostly based on the few known miRNA:target gene interactions.The need for a functional assay to identify the miRNA target is the need of the hour.
We have developed a novel functional assay to enable identification of functional miRNA targets. In a pilot project we used mir130a and its verified target v-maf musculoaponeurotic fibrosarcoma oncogene homolog B(MAFB)as a proof of concept,this identified a further panel of mir130a targets none of which were identified as potential targets of mir130a by the available target pridiction programmes.
Tel:
020 7848 5839
Email:
Interests:
Research focusses on the development of enzymes capable of delivering targeted cytosine methylation to predetermined DNA sequences. We are using these enzymes to simulate the methylation patterns observed in cancer patients, to determine the actual role of DNA methylation in disease progression. An additional and emerging basic research program seeks to address the effects of gene mutations associated with epigenetic components of the cell, that are being increasingly found in leukaemia patients, in the desease process.
Tel:
0208 848 5839
Email:
Interests:
My research focus is the study of immune dysfunction in leukaemia and immune reconstitution after allogeneic haematopoietic stem cell transplantation. My research group performs comprehensive phenotypic and functional studies of immunity in patients with leukaemia and allogeneic haematopoietic stem cell transplant patients with the aim of identifying signatures indicative of beneficial and detrimental clinical courses. Knowledge obtained will enable improved monitoring of patients to facilitate rapid and tailored treatment regimens and development of novel specific immunotherapeutic strategies.
Tel:
020 7848 5208
Email:
Website:
Interests:
• Normal Haemopoiesis and abnormalities in the myelodysplastic syndromes (MDS) and myeloid leukaemias
• Cell cycle (particular focus on G0→G1→S-phase transitions)
• Systems Biology analyses of protein interaction networks
• Epigenetics (study of specific and genome-wide DNA CpG methylation, histone code and nucleosome positioning)
• Cell cycle (particular focus on G0→G1→S-phase transitions)
• Systems Biology analyses of protein interaction networks
• Epigenetics (study of specific and genome-wide DNA CpG methylation, histone code and nucleosome positioning)
Tel:
(office) +44 (0)207 848 5818 (lab) +44 (0)207 848 5808 or 5830
Email:
Interests:
My research is mainly focused in multiple myeloma, a haematological malignancy characterised by accumulation of plasma cells in the bone marrow. It is becoming increasingly evident that the interaction of the tumour myeloma plasma cells with the bone marrow microenvironment is essential for the development of the disease. The pattern of expression of cell adhesion molecules and the secretion of soluble factors by both myeloma plasma cells and other bone marrow cells (fibroblasts, osteoclasts, osteoblasts, endothelial cells, etc) create a network of signals that promote malignant cells survival. These processes require the recruitment of bone marrow cells and myeloma cells to niches within the bone marrow that allow cell-cell and cell-extracellular matrix interactions that trigger these network of signals. In addition, myeloma cells can become resistant to therapeutic treatments targeting cell proliferation and survival by increasing their adhesive properties to extracellular matrix proteins. Our research is focused in increasing our understanding of the adhesion and migratory patterns of both myeloma and other bone cells and the signalling pathways involved in these processes to search for targets to develop new therapeutic agents for multiple myeloma.
Tel:
+ 44 (0) 20 7848 5816
Email:
Our research centres on the pathophysiology of the haemoglobin disorders – the thalassaemias and sickle cell disease – diseases that have a major global impact on public health.
Both these disorders display a remarkable diversity in their clinical severity. A major ameliorating factor is the innate ability to produce fetal haemoglobin (HbF). Using classical twin studies, we have shown that HbF levels are predominantly genetically controlled and that almost 60 per cent of the trait variance is accounted for by genetic factors outside the globin locus. Through linkage analyses and association studies we have discovered two of the three major quantitative trait loci (QTLs) for HbF variability known to date. Loci identified by us are on chromosomes 6q and 2p (BCL11A) and are involved in the control of haematopoiesis as well as of HbF production in adults. Several other loci are currently being validated.
The 6q QTL itself consists of single nucleotide polymorphisms (SNPs) distributed in three linkage disequilibrium (LD) blocks in an intergenic region, between genes MYB and HBS1L. Our expression profiling studies have shown that quantitative differences in MYB are key to the control of HbF levels. The transcriptional control of MYB is poorly understood, despite it being an important transcription factor involved in oncogenesis and hematopoiesis. Our studies have shown that the HBS1L-MYB interval contains regulatory sequences. We have begun characterisation of the intergenic QTL to determine how it regulates expression of the flanking genes; this will enable us to determine a functional basis for the genetic association with raised HbF levels.
Our investigation of BCL11a (the 2p QTL) is now also underway. Early investigations reveal a complex pattern of splice forms and intronic polymorphisms, which may explain the role of this gene in erythroid development and thus HbF levels.
Eventually we hope to delineate the genetic architecture of fetal haemoglobin control in adults and identify the loci and sequence variants that explain most of the trait variance in adults. The identification of these HbF QTLs will have implications for novel therapeutic options, more accurately informed genetic counselling, and improving predictive accuracy of disease severity in these haemoglobinopathies, and ultimately, improving patient management. Our work on dissection of the genetic architecture of HbF inheritance has contributed significantly towards understanding of genetic modifiers for monogenic disorders and complex traits in general.
The 2 major QTLs, HMIP on 6q and BCL11A on 2p, together with a SNP in the β globin cluster accounts for about 50% of the variability in HbF levels in adults, allowing us to make a prediction on an individual’s ability to produce HbF based on this genetic information.
Our work on dissecting genotype/phenotype relationship in the thalassaemias has also contributed significantly to DNA diagnostics in the haemoglobinopathies and unravelling the molecular basis of the unusual beta thalassaemias.
There is also an ongoing programme of clinical trials in sickle cell disease, including assessment of novel therapeutic agents and interventions. The role of environmental factors in determining the phenotype of sickle cell disease is also studied, together with the identification of useful biomarkers.
Both these disorders display a remarkable diversity in their clinical severity. A major ameliorating factor is the innate ability to produce fetal haemoglobin (HbF). Using classical twin studies, we have shown that HbF levels are predominantly genetically controlled and that almost 60 per cent of the trait variance is accounted for by genetic factors outside the globin locus. Through linkage analyses and association studies we have discovered two of the three major quantitative trait loci (QTLs) for HbF variability known to date. Loci identified by us are on chromosomes 6q and 2p (BCL11A) and are involved in the control of haematopoiesis as well as of HbF production in adults. Several other loci are currently being validated.
The 6q QTL itself consists of single nucleotide polymorphisms (SNPs) distributed in three linkage disequilibrium (LD) blocks in an intergenic region, between genes MYB and HBS1L. Our expression profiling studies have shown that quantitative differences in MYB are key to the control of HbF levels. The transcriptional control of MYB is poorly understood, despite it being an important transcription factor involved in oncogenesis and hematopoiesis. Our studies have shown that the HBS1L-MYB interval contains regulatory sequences. We have begun characterisation of the intergenic QTL to determine how it regulates expression of the flanking genes; this will enable us to determine a functional basis for the genetic association with raised HbF levels.
Our investigation of BCL11a (the 2p QTL) is now also underway. Early investigations reveal a complex pattern of splice forms and intronic polymorphisms, which may explain the role of this gene in erythroid development and thus HbF levels.
Eventually we hope to delineate the genetic architecture of fetal haemoglobin control in adults and identify the loci and sequence variants that explain most of the trait variance in adults. The identification of these HbF QTLs will have implications for novel therapeutic options, more accurately informed genetic counselling, and improving predictive accuracy of disease severity in these haemoglobinopathies, and ultimately, improving patient management. Our work on dissection of the genetic architecture of HbF inheritance has contributed significantly towards understanding of genetic modifiers for monogenic disorders and complex traits in general.
The 2 major QTLs, HMIP on 6q and BCL11A on 2p, together with a SNP in the β globin cluster accounts for about 50% of the variability in HbF levels in adults, allowing us to make a prediction on an individual’s ability to produce HbF based on this genetic information.
Our work on dissecting genotype/phenotype relationship in the thalassaemias has also contributed significantly to DNA diagnostics in the haemoglobinopathies and unravelling the molecular basis of the unusual beta thalassaemias.
There is also an ongoing programme of clinical trials in sickle cell disease, including assessment of novel therapeutic agents and interventions. The role of environmental factors in determining the phenotype of sickle cell disease is also studied, together with the identification of useful biomarkers.
Website:
Interests:
Clinical and molecular characterisation of red cell disorders; sickle cell disease and haemoglobinopathies.
Tel:
0203 299 3242
Email:
Website:
Interests:
Genetic mapping of measurable (quantitative) traits in humans; disease and trait inheritance in families, population-genetic basis of ethnic trait differences.
Email:
Website:
Interests:
Our research centres on the pathophysiology of the beta haemoglobin disorders - the beta thalassaemias and sickle cell disease - diseases that have a major global impact on public health. Both these disorders display a remarkable diversity in their clinical severity, a major ameliorating factor is the innate ability to produce fetal haemoglobin (HbF, alpha2y2). Using classical twin studies, we showed that HbF levels are predominantly genetically controlled, and that almost 60 percent of the trait variance is accounted for by genetic factors outside the beta globin locus. We are at the forefront of identifying the genetic loci controlling fetal haemoglobin. Through linkage analyses and association studies we have identified 2 quantitative trait loci (QTLs) on chromosomes 6q and 8q, involved in the control of fetal haemoglobin production in adults, with several others currently being validated. Recently, our expression profiling studies have shown that quantitative difference in the cMYB transcription factor is key to the control of (HbF) levels. The cMYB gene lies within our 6q QTL candidate interval. We have identified single nucleotide polymorphisms (SNPs) in three linkage disequilibrium (LD) blocks within the intergenic interval between HBS1 L and cMYB on 6q that are highly associated with high F cells. Eventually we hope to delineate the genetic architecture of fetal haemoglobin control in adults and identify the loci and sequence variants that explain most of the trait variance in adults. The identification of these HbF QTLs will have implications for novel therapeutic options, more accurately informed genetic counselling, and improving predictive accuracy of disease severity in these beta haemoglobinopathies, and ultimately, improving patient management. Our work on dissection of the genetic architecture of HbF inheritance has contributed significantly towards understanding of genetic modifiers for other monogenic disorders and complex traits. Beta thalassaemia is typically inherited as haploinsufficient Mendelian recessives but atypical forms, in which inheritance of a single copy of Beta thalassaemia allele resulting in moderately severe anaemia, have been described. The molecular mechanisms underlying these so-called 'dominantly inherited Beta thalassaemias' have puzzled many for a long time. We could demonstrate that such dominantly inherited forms of Beta thalassaemia were due to hyper-instability of the Beta chain variants. We could also demonstrate that some of these autosomal dominant Beta thalassaemias are caused by failure of the surveillance mechanism of the nonsense mediated decay (NMD) pathway due to position effects of the mutations in relation to the gene sequence. Our work on dissecting genotype / phenotype relationship in the Beta thalassaemias has also contributed significantly to DNA diagnostics in the haemoglobinopathies. There is also an ongoing programme of clinical trials in sickle cell disease, involving the assessment of novel therapeutic agents and interventions. The role of environmental factors in determining the phenotype of sickle cell disease is also being studied, together with the identification of useful biomarkers.
Tel:
020 7848 5443; 020 3299 1679
Email:
Website:
The Section of Research Oncology has as a central albeit non-exclusive theme of the pathobiology of breast cancer. Substantial activity surrounds cellular, genetic and proteomic studies on patient breast tumour samples, as well as exploitation of the derived data in the form of basic biological insights and (immuno) therapies. Additional areas of research strength are in novel imaging techniques, pathophysiology of lymphoedema, cancer outcomes and global oncopolicy.
Work of the Section includes:
- Breast Cancer Biology Group
- Breakthrough Breast Cancer Research Unit
- Breast Pathology Research Group
- Breast Cancer Stem Cell Biology Group
- Breast Cancer Surgical Group
- Epidemiology & Oncopolicy Group
- Phase 1 Trials.
Website:
Interests:
Andrew Tutt is a Consultant Clinical Oncologist and Director of the Breakthrough Breast Cancer Research Unit and a Professor of Oncology at King's College London. After training at the Royal Marsden Hospital, he worked with Professor Alan Ashworth at the Institute of Cancer Research, where he described the DNA repair functions of the BRCA2 breast cancer predisposition gene. He practises clinical oncology at Guy's Hospital and has developed a translational clinical trial programme focusing on cancers associated with functional deficiencies in BRCA1 and BRCA2. His interests involve the discovery of novel therapies in BRCA1/BRCA2-associated cancers and ER/HER2-negative/basal-like breast cancers—including the identification of poly(ADP-ribose) polymerase (PARP) as an exciting new target for therapy in these areas. He is chief investigator for the international BRCA and Triple Negative Breast Cancer Trials (TNT) and the phase II ICEBERG proof of concept trials of PARP inhibition with Olaparib in BRCA1 and BRCA2 carriers. He leads a neo-adjuvant trial initiative for Triple Negative Breast Cancer in Breast International Group Neo-BIG program. Dr Tutt's laboratory research interests focus on the identification and validation of potential treatment targets and biomarkers for women with Triple Negative Breast Cancer.
Tel:
020 7188 9881
Email:
Website:
Interests:
My goal is to drive high quality clinical & translational research that directly impacts on breast cancer patients. Key areas of research are in cancer metastasic spread, cancer stem cells, pathophysiology of lymphoedema, sentinel lymph node biopsy, terahertz imaging, cancer and evolutionary biology & cancer outcomes.
Tel:
020 7188 3027
Email:
Interests:
Biobanking; translation studies relating to histopathological application; markers of proliferative activity.
Email:
Email:
Website:
Interests:
The Mammary stem cell biology group focuses on characterization of normal and malignant mammary stem cells in order to elucidate their role in cancer initiation and progression.
Developing an experimental framework appropriate for the study of stem cells of human origin is one of the priorities of the group and an ongoing effort. Novel experimental systems are employed to understand the molecular mechanisms that govern cell fate decisions and to identify defects in these mechanisms that can lead to transformation. The ultimate goal of these studies is to develop clinical applications based on stem cell biology concepts and to explore their translational potential in cancer diagnosis, prognostication, therapy and
prevention.
Tel:
020 7188 1296
Email:
Website:
Interests:
Phase I trials of novel agents in solid tumours; clinical development of new therapies for lung cancer and mesothelioma; discovery and development of antibody immunotherapies; pharmacogenetics.
Tel:
020 7188 4260
Email:
Interests:
The aetiology, prevention and treatment of upper gastrointestinal cancers, particularly oesophageal cancer, are my main fields of interest. I use a broad range of methodological approaches to address these issues, including translational studies, epidemiological methods, clinical investigations and risk factor evaluations.
The overarching aim of this research plan is that it will result in a decreased death and suffering from oesophageal adenocarcinoma, including the gastro-oesophageal junction (OAC). Basic scientists, surgeons, oncologists, gastroenterologists, radiologists, pathologists, psychologists, nurses, dieticians, epidemiologists, and biostatisticians will collaborate in a multidisciplinary approach to address this aim.
I wish to develop the epidemiological and clinical research in this field. By consolidating my research activities at two universities, Karolinska Institutet in Sweden and King’s College London in the United Kingdom, it will be possible to take advantage of the special prerequisites and data sources available in these countries. In Sweden and the other Nordic countries there are excellent opportunities for ground-breaking population-based research by virtue of the personal identity numbers, the well maintained registries of diseases and health care, and the complete follow-up for e.g. cancer risk and mortality. In the United Kingdom, the research group has access to a high-volume centre for the treatment of oesophageal cancer, which enables comprehensive and complex data collections for translational and clinical research, including randomised clinical trials.
The overarching aim of this research plan is that it will result in a decreased death and suffering from oesophageal adenocarcinoma, including the gastro-oesophageal junction (OAC). Basic scientists, surgeons, oncologists, gastroenterologists, radiologists, pathologists, psychologists, nurses, dieticians, epidemiologists, and biostatisticians will collaborate in a multidisciplinary approach to address this aim.
I wish to develop the epidemiological and clinical research in this field. By consolidating my research activities at two universities, Karolinska Institutet in Sweden and King’s College London in the United Kingdom, it will be possible to take advantage of the special prerequisites and data sources available in these countries. In Sweden and the other Nordic countries there are excellent opportunities for ground-breaking population-based research by virtue of the personal identity numbers, the well maintained registries of diseases and health care, and the complete follow-up for e.g. cancer risk and mortality. In the United Kingdom, the research group has access to a high-volume centre for the treatment of oesophageal cancer, which enables comprehensive and complex data collections for translational and clinical research, including randomised clinical trials.
Email:
Interests:
The CAR mechanics lab is focussed upon development of novel genetic strategies to target T-cell specificity against diverse malignancies. The approach we use entails the construction of cDNAs that encode for fusions known as Chimeric Antigen Receptors (CARs). These molecules couple the ability to target native tumour antigens to delivery of a tailored T-cell activating signal. Delivery to polyclonal peripheral blood T-cells is achieved using retroviral or lentiviral vectors. In a parallel theme, we are developing systems to target other lymphoid cell populations against cancer, including natural killer and gamma delta T-cells. Our first clinical trial of CAR-based immunotherapy is scheduled for 2012 and will involve the treatment of patients with squamous cell carcinoma of head and neck.
Recent Publications:
1. Maher J, Brentjens RJ, Gunset G, Riviere I, Sadelain M (2002) Human T lymphocyte cytotoxicity and proliferation directed by a single chimeric TCR/ CD28 receptor. Nature Biotechnology 20: 70-75. http://www.ncbi.nlm.nih.gov/pubmed/11753365
2. Maher J and Davies ET (2004). Targeting cytotoxic T-lymphocytes for cancer immunotherapy. British Journal of Cancer 91, 817-821. http://www.ncbi.nlm.nih.gov/pubmed/15266309
3. Lo AS, Gorak-Stolinska P, Bachy V, Ibrahim MA, Kemeny DM, Maher J (2007) Modulation of dendritic cell differentiation by colony-stimulating factor-1: role of phosphatidylinositol 3'-kinase and delayed caspase activation. Journal of Leukocyte Biology 82: 1446-54. http://www.ncbi.nlm.nih.gov/pubmed/17855501
4. Lo A, Taylor J, Farzaneh F, Kemeny DM, Dibb NJ, Maher J (2008) Harnessing the tumour-derived cytokine, colony-stimulating factor-1, to co-stimulate T-cell growth and activation. Molecular Immunology 45: 1276-87. http://www.ncbi.nlm.nih.gov/pubmed/17950877
5. Wilkie S, Picco G, Foster J, Davies DM, Julien S, Cooper L, Arif S, Mather SJ, Taylor-Papadimitriou J, Burchell JM, Maher J (2008) Re-targeting of human T-cells to tumour-associated MUC1 – the evolution of a chimeric antigen receptor. Journal of Immunology 180: 4901-9. http://www.ncbi.nlm.nih.gov/pubmed/18354214
6. Maher J, Wilkie S (2009) CAR mechanics: Driving T-cells into the MUC of Cancer. Cancer Research 69: 4559-62. http://www.ncbi.nlm.nih.gov/pubmed/19487277
7. Davies DM, Maher J (2010) Adoptive T-cell immunotherapy of cancer using chimeric antigen receptor-grafted T-cells. Arch Immunol Ther Exp. 58: 165-178. http://www.ncbi.nlm.nih.gov/pubmed/20373147
8. Wilkie S, Burbridge S, Chiapero-Stanke L, Parente-Pereira AC, Cleary S, van der Stegen JC, Spicer J, Davies DM, Maher J (2010) Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. Journal of Biological Chemistry. 285: 25538-44. http://www.ncbi.nlm.nih.gov/pubmed/20562098
9. Parente-Pereira AC, Burnet J, Ellison D, Foster J, Davies DM, van der Stegen C, Burbridge S, Chiapero-Stanke L, Wilkie S, Mather S, Maher J. (2011) Trafficking of CAR-engineered human T-cells following regional or systemic adoptive transfer in SCID Beige mice. Journal of Clinical Immunology. In press. http://www.ncbi.nlm.nih.gov/pubmed/21505816
Tel:
020 7188 1468
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The Breast Cancer Biology Group is committed to translational research. It studies the molecular and phenotypic changes that occur in breast cancer with the aim of translating the findings into clinical applications.The laboratory has a particular focus on
two molecules, MUC1 and JARID1B/KDM5, both of which were discovered by the
laboratory.
The studies on MUC1 have led to investigations into changes in glycosylation
that occur in breast cancer. This field has greatly influenced the immunology
studies and we are actively exploring the binding of tumour-associated glycoforms of MUC1 with lectin-like receptors of the immune system. We are also studying of auto-antibodies reactive with MUC1 tumour-associated glycopeptides in breast cancer patients, and their correlation with prognosis. The involvement of aberrant O-linked glycosylation in the development and progression of breast cancers is also a major focus.
JARID1B/KDM5 is a histone demethylase that is expressed in breast cancers and the developing mammary gland while expression in other normal tissues is limited to the testis. These studies centre around its function in normal mammary gland development and in breast cancer and has led to an interest in epigenetic of breast cancer.
Glycosylation
The change to malignancy is associated with changes in the glycans attached to glycolipids and glycoproteins and evidence is now accumulating that this can have a fundamental effect on the tumour cell. The particular form glycosylation of proteins that we are studying is O-linked glycosylation, where glycans are O-linked to serine and/or threonine and the sugars are added individually and sequentially. This type of glycosylation is found on mucin-type molecules or glycoproteins containing mucin-like domains. Our previous work has demonstrated that changes in the expression of glycosyltransferases in breast carcinomas compared to normal breast epithelial can explain, at least in part, the changes in O-linked glycans observed in breast cancers. In particular, two sialyltransferases are upregulated at the RNA level.
We have particularly been studying the membrane mucin known as MUC1, which is
upregulated and aberrantly expressed in breast and other carcinomas. The staining of an antibody that specifically recognises MUC1 carrying tumour-associated glycans shows that greater than 90% of breast carcinomas aberrantly glycosylate their O-linked glycans, suggesting that this may elicit some benefit to the tumour.
Projects
We are looking at how particular tumour-associated glycoforms of MUC1 interact with immune cells to stimulate an immune response and suppress an immune response.
We also plan to map histone marks in progenitor and differentiated cells of the
mammary gland and integrate these with gene expression.
two molecules, MUC1 and JARID1B/KDM5, both of which were discovered by the
laboratory.
The studies on MUC1 have led to investigations into changes in glycosylation
that occur in breast cancer. This field has greatly influenced the immunology
studies and we are actively exploring the binding of tumour-associated glycoforms of MUC1 with lectin-like receptors of the immune system. We are also studying of auto-antibodies reactive with MUC1 tumour-associated glycopeptides in breast cancer patients, and their correlation with prognosis. The involvement of aberrant O-linked glycosylation in the development and progression of breast cancers is also a major focus.
JARID1B/KDM5 is a histone demethylase that is expressed in breast cancers and the developing mammary gland while expression in other normal tissues is limited to the testis. These studies centre around its function in normal mammary gland development and in breast cancer and has led to an interest in epigenetic of breast cancer.
Glycosylation
Glycosylation of proteins is one of the most common forms of post-translational modification and affects many cellular functions including cell:cell interactions, cell:matrix interactions, molecular recognition as well as the stability and folding of proteins. Thus for a cell to have a "normal" behaviour its glycosylation machinery must be working correctly.
The change to malignancy is associated with changes in the glycans attached to glycolipids and glycoproteins and evidence is now accumulating that this can have a fundamental effect on the tumour cell. The particular form glycosylation of proteins that we are studying is O-linked glycosylation, where glycans are O-linked to serine and/or threonine and the sugars are added individually and sequentially. This type of glycosylation is found on mucin-type molecules or glycoproteins containing mucin-like domains. Our previous work has demonstrated that changes in the expression of glycosyltransferases in breast carcinomas compared to normal breast epithelial can explain, at least in part, the changes in O-linked glycans observed in breast cancers. In particular, two sialyltransferases are upregulated at the RNA level.
We have particularly been studying the membrane mucin known as MUC1, which is
upregulated and aberrantly expressed in breast and other carcinomas. The staining of an antibody that specifically recognises MUC1 carrying tumour-associated glycans shows that greater than 90% of breast carcinomas aberrantly glycosylate their O-linked glycans, suggesting that this may elicit some benefit to the tumour.
Projects
There are various projects within the laboratory looking at the affect of changes in glycosylation on tumour cells and on the tumour environment, and studying the function of JARID1B/KDM5 We are investigating the how the changes in O-linked glycosylation affects the development of mammary cancer using model systems.
We are investigating thehow O-linked glycosylation affects the progression of breast cancer and if the expression of particular glycosylated proteins can influence the site of metastasis.
We are looking at how particular tumour-associated glycoforms of MUC1 interact with immune cells to stimulate an immune response and suppress an immune response.
JARID1B binds to the estrogen receptor and so we are investigating the function of JARID1B and its role in estrogen receptor signalling.
We also plan to map histone marks in progenitor and differentiated cells of the
mammary gland and integrate these with gene expression.
Tel:
020 7188 1470
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Mr Michael Douek's translational research program evaluates novel devices and imaging modalities to improve breast surgery for cancer. This includes the clinical applications of nanotechnology for sentinel node biopsy, intraoperative radiotherapy and novel devises for breast reconstruction.
Mr Douek is the Chief Investigator of the SentiMAG trial of sentinel node biopsy and of the POBRAD trial (prospective trial of acellular dermal matrix for implant breast reconstruction). He is also Principal Investigator for the international randomised controlled trial of intra-operative radiotherapy (TARGIT trial), at Guys Hospital.
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Sarah E Pinder is Professor of Breast Pathology at Kings College London and Lead Consultant Breast Pathologist at Guy’s and St Thomas’s Hospitals.
She serves on the Cancer Research UK Biomarkers in Clinical Trials Committee, the National Cancer Intelligence Network (NCIN) Breast Reference Group, the NHS Breast Screening Programme Pathology Co-ordinating Committee, the Sloane Project (UK National DCIS audit) Steering Group and Chairs the NHS Breast Screening Programme Pathology Research Committee. She is Associate Editor for Breast for Histopathology.
Her research interests are focused on breast cancer diagnosis and prediction of prognosis, with a particular interest in precursor lesions, with emphasis on correlation of the morphology, protein expression and molecular and genetic features. She leads the KCL Breast Research Pathology Group and the Breakthrough Breast Cancer Research Unit’s investigation into the molecular pathology and biology of the precursors of invasive breast carcinoma, particularly of basal-like type.
She has published over 190 peer-reviewed articles, over 50 invited reviews, and more than 40 chapters on breast diseases in medical textbooks.
She serves on the Cancer Research UK Biomarkers in Clinical Trials Committee, the National Cancer Intelligence Network (NCIN) Breast Reference Group, the NHS Breast Screening Programme Pathology Co-ordinating Committee, the Sloane Project (UK National DCIS audit) Steering Group and Chairs the NHS Breast Screening Programme Pathology Research Committee. She is Associate Editor for Breast for Histopathology.
Her research interests are focused on breast cancer diagnosis and prediction of prognosis, with a particular interest in precursor lesions, with emphasis on correlation of the morphology, protein expression and molecular and genetic features. She leads the KCL Breast Research Pathology Group and the Breakthrough Breast Cancer Research Unit’s investigation into the molecular pathology and biology of the precursors of invasive breast carcinoma, particularly of basal-like type.
She has published over 190 peer-reviewed articles, over 50 invited reviews, and more than 40 chapters on breast diseases in medical textbooks.
Tel:
020 7188 4260
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My lab is interested in understanding how membrane trafficking machineries can contribute toward cancer. We are currently studying a molecular complex called ESCRT (Endosomal Sorting Complex Required for Transport) that is required for completion of cell division and for the degradation of growth factor receptors such as the EGFR and examining how defects in ESCRT function can drive tumourigenesis.
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Email:
Tel:
+44 (0)20 7188 7904
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