Cancer Studies (Research Division)

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MPhil/PhD

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Part Time, Full Time

RESEARCH PROFILE

2008 RAE Result: 67 per cent of research outputs from the Division were rated as world leading or internationally excellent

Research income: over £10 million in 2012-13

Current number of academic staff: 40

Current number of research students: PhD 36 FT, 21 PT

Recent publications:

  • Philippe Riou; Svend Kjaer; Ritu Garg; Andrew Purkiss; Roger George; Robert J Cain; Ganka Bineva; Nicolas Reymond; Brad McColl; Andrew J Thompson; Nicola O'Reilly; Neil Q McDonald; Peter J Parker*; Anne J Ridley*. 14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to regulate Rnd proteins (2013) Cell Volume 153, Issue 3, 25 April 2013, Pages 640-653 *Joint corresponding authors
  • Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, Lu K, Schmutzler RK, Matulonis U, Wickens M, Tutt A (2010) Oral PARP inhibitor olaparib (AZD2281; KU-0059436) in patients with BRCA1 or BRCA2 mutation carriers with recurrent ovarian cancer: a proof of concept trial. The Lancet 376(9737):245-51.
  • Yeung J, Esposito MT, Gandillet A, Zeisig BB, Griessinger E, Bonnet D, So CW (2010). β-catenin mediates the establishment and drug resistance of MLL leukemic stem cells. Cancer Cell Vol. 18 (6): 606-18.
  • Makani J*, Menzel S*, Nkya S, Cox SE, Drasar E, Soka D, Komba AN, Mgaya J, Rooks H, Vasavda N, Fegan G, Newton CR, Farrall M, Thein SL. Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia. Blood. 2011 Jan 27;117(4):1390-2
  • Lüchtenborg M, Riaz S, Coupland V, Lim E, Jakobsen E, Krasnik M, Page R, Lind M, Peake M, and Møller H (2013). High Procedure Volume Is Strongly Associated With Improved Survival After Lung Cancer Surgery. JCO. JCO.2013.49.0219; published online on July 29, 2013;

KEY FACTS
Student destinations
Over 85 per cent of students under the primary supervision of Divisional staff continued in academic and medical research taking Post-Doctoral or more senior positions. The remaining students have taken commercial positions.
Head of group/division
Professor Peter Parker FRS
Duration
Expected to be usually three years full-time or up to six years part-time. Enrolment is available in October, January, April and July each year.
Location
Guy's, St Thomas' and Denmark Hill campuses.
Year of entry 2015
Offered by
Faculty of Life Sciences & Medicine
Closing date
Named studentships will have a closing date stipulated on the advertisement. Self-funded students or those that have secured a personal scholarship should apply at least three months before their proposed starting date but it is recommended that you are in touch with the Division before submitting an online application.
Intake
No set number.
Fees
CONTACTS
Contact information
Division Manager, tel +44 (0)20 7848 8300, fax +44 (0)20 7848 6220.
Email Website

RESEARCH DESCRIPTION
The Division of Cancer Studies has a multidisciplinary research portfolio that maps onto and spans the entire patient journey. We bring together and are underpinned by core strengths in haematology, haemato-oncology, breast cancer biology, epidemiology, cancer cell biology, gastro-intestinal cancer and oncopolicy.  We are fortunate to have access to unique resources such as our Bio-Bank.

The strategic objective of the Division is to foster a culture of innovation in patient care through research excellence. To achieve this we are working towards fully integrated research pathways, breaking down traditional clinical/academic boundaries and drawing together members of the Division and colleagues from our associated Hospital Trusts. This is reflected in the coordinated strategic planning that has laid the foundations for our Integrated Cancer Centre.

There are six Research Sections within the Division:
  • Cancer Epidemiology and Population Health
  • Cell Biology and Imaging
  • GI Cancer
  • Haemato-oncology
  • Molecular Haematology
  • Research Oncology


Staff interests associated with the research programme and its research groups

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+44 (0)20 7848 6616
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Our research is interested in Cancer Immunotherapy. We wish to understand the mechanisms by which tumours can suppress or evade the immune system. We hope that identifying and investigating these mechanisms will uncover novel therapeutic targets which can be modulated to allow an anti-tumour immune response to effectively attack the tumour tissue.

Our current focus in on the tumour stroma, in particular, tumour associated macrophages which get recruited and aid tumour progression. These cells have potent immune suppressive properties which we are currently investigating.

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+44 20 7848 6415
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The Institute of Cancer Policy has an internationally recognised faculty and global program of research into all aspects of cancer policy from childhood cancers, through to global cancer surgery and socio technological studies of cancer technologies, including medicines in collaboration with Social Science, Health and Medicine.
We accept both desk and field research program's and have an active capability enhancement program directly with specific countries eg India, Georgia et al, and through our work with the Centre for Global Health at Kings, e.g. Sierra Leone.
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07720398401
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Cancer Epidemiology and Population Health
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Quantitative and qualitative studies on patient experience, cancer inequalities, end of life care. The role of medical humanities in improving medical education and care.

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02071888414
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020 7378 9510
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Our group pursues two main lines of investigation:

The first aims at characterizing the properties of cancer genes, which are genes that contribute to cancer upon acquiring modifications in their sequence and/or structure. We discovered that cancer genes have evolutionary and systems-level properties that distinguish them from other human genes (Rambaldi et al, Trends in Genet, 2008; D’Antonio & Ciccarelli PLoS Comp Biol, 2011). We used this knowledge to identify novel cancer genes (D’Antonio & Ciccarelli Genome Biol, 2013) and to identify negative genetic partners of cancer genes (D’Antonio et al Cell Reports, 2013). These data are stored in a highly accessed public resource (http://ncg.kcl.ac.uk/). 

The second line involves extensive cancer genome sequencing to characterize the evolution of cancer clones. By deep-sequencing DNA from peripheral blood, we showed that the genome of cancer patients with mismatch repair deficiency is constitutively unstable, thus suggesting that it is predisposed to acquire the second hit (De Grassi et al, PLoS Biol, 2010). More recently, we profiled the genome of paediatric liver cancers. We observed no mutation instability as opposed to high chromosomal instability that often leads to deregulation of the JNK pathway, which is the driver of cancer progression (Iannelli et al, Nature Comm, 2014).
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+44 (0)20 7848 6616
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Cancer epidemiology and analysis of cancer care and outcomes at the population level.
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020 7188 8414
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020 7378 9510
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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). 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.
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020 7188 9286
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020 7188 9986
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Dr Luchtenborg's interest are mainly focussed on the patient and treatment related factors that affect the survival of cancer patients, and lung cancer patients in particular. Most studies she is involved in are carried out using the national cancer registration data, and are conducted in collaboration with Public Health England's National Cancer Intelligence Network.

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+44 (0)20 7188 8414
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Dr Van Hemelrijck mainly works on prostate cancer and coordinates King’s Health Partners Prostate Cancer Research Network. This Network brings together all researchers and clinicians involved in prostate cancer research at KHP. In addition, Mieke has an interest in metabolic and inflammatory biomarkers and risk of all types of cancer. She leads the Patho-Epidemiology Group together with Professor Massimo Loda. Apart from facilitating tissue collection from all men diagnosed with prostate cancer at KHP, the group works closely with KHP Prostate Cancer Research Network to serve and research the large and unique prostate cancer population of South-East London. Together they aim to improve the ongoing research on distinguishing indolent from fatal prostate cancer. In particular, Mieke is interested in how the lipid metabolism is associated with risk and progression of prostate cancer with a specific focus on serum lipid biomarkers.

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+44 (0)20 7188 7904
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The Institute of Cancer Policy has an internationally recognised faculty and global program of research into all aspects of cancer policy from childhood cancers, through to global cancer surgery and socio technological studies of cancer technologies, including medicines in collaboration with Social Science, Health and Medicine. 
We accept both desk and field research program's and have an active capability enhancement program directly with specific countries eg India, Georgia et al, and through our work with the Centre for Global Health at Kings, e.g. Sierra Leone. 
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07720398401
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Cell Biology & Imaging
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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.
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020 7848 8769
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020 7848 6220
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Cancer, kinase signalling pathways, PSKs, apoptosis, cytoskeleton, cell shape, migration, cell cycle and prostate
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Our research is interested in Cancer Immunotherapy. We wish to understand the mechanisms by which tumours can suppress or evade the immune system. We hope that identifying and investigating these mechanisms will uncover novel therapeutic targets which can be modulated to allow an anti-tumour immune response to effectively attack the tumour tissue.

Our current focus in on the tumour stroma, in particular, tumour associated macrophages which get recruited and aid tumour progression. These cells have potent immune suppressive properties which we are currently investigating.
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+44 20 7848 6415
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My laboratory is interested in the cell biology underlying two fundamental cellular processes - receptor downregulation and cell division. These processes are linked by the functions of a membrane trafficking apparatus – the Endosomal Sorting Complex Required for Transport (ESCRT) machinery – that is essential for their completion. In both cases, the ESCRT machinery performs a topologically unique membrane remodeling to allow endosomal sorting or release of daughter cells during cytokinesis.

Defects in ESCRT-function are thought to produce failures in the termination of growth factor receptor signaling or to produce defects in cell division. We are using molecular biology, advanced imaging (fixed and live) and molecular biology and biochemical techniques to understand how this machinery functions and to explore the consequences of its deregulation in cancer.
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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 complete miotosis, divide and proliferate. Current projects are employing a wide range of different cell and molecular biology techniques, as well as small molecule inhibitors, to investigate how PSKs act mechanistically to perform their functions and regulate the cell cytoskeleton. A key goal for the laboratory is to evaluate these proteins as therapeutic targets suitable for drug inhbition and the treatment of cancer.
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020 7848 8302
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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.
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020 7848 6835
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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.

The nature of my work is, by definition, multidisciplinary and we work on a broad range of projects for example:
High content screening of protein-protein interactions: I have been involved in an initiative to develop ‘optical proteomic technology for in situ analysis of protein interaction networks’. This collaboration, involving a number of research groups within the college, aimed to develop high-throughput/content optical screening approaches for cell based assays of protein-protein interactions. Such a development of high-throughput screening (HTS) for protein-protein and protein-effecter interactions represents a paradigm shift in proteomics technology. We have developed a simplified, open architecture, microscope platform with both wide-field steady-state anisotropy (using a QuadView Image Splitter) and laser scanning TCSPC fluorescence lifetime imaging modes. The rather surprising outcome of this work is that the acceptor anisotropy methodology compares very favourably with the more established donor FLIM methods that we had been using to date. We have recently shown that measurements of FRET by FLIM and anisotropy are correlated in high-content screens of inhibitor and siRNA libraries. The great advantage of the acceptor anisotropy method is that it is much faster; a 96 well plate taking just 30 mins by acceptor anisotropy compared to 10 hours using donor FLIM.

For proteomic screens of protein-protein interactions, a need for high-throughput screening of (potentially) millions of constructs is very clear. Without a significant advance in either parallelisation (improvement in widefield techniques to provide the required temporal resolution) or counting rate for time-correlated single photon counting technologies (currently limited to ~5 million events per second dependent on hardware and excitation rate) it is clear that laser scanning microscopy will not fulfil this need for adherent cell assays. Conversely, HTP screening using flow cytometry techniques is very much more tractable. Our group has developed a microfluidics based flow cytometer for FRET based screening applications. The concept of the system is very simple and relies on the flow of cells though a focused laser beam. The fluorescence excited in the cells containing fluorescent proteins or labelled with antibodies is detected using the burst integrated fluorescence lifetime technique.

Development of Multiphoton Microscopy: The group has been involved in the development of Multiphoton fluorescence lifetime imaging for over 10 years. We have 3 systems for development and appplications.

Following our success in obtaining research funding for the Cancer Research UK, Comprehensive Cancer Imaging Centre we have a programme of work to investigate adaptive optics (AO) in multiphoton microscopy. The group is developing a multiphoton FLIM microscope examining both feedback controlled AO optimisation and a sensor based method for mapping the optical aberrations. A collaboration with Frederick Geissman (Centre for Molecular & Cellular Biology of Inflammation) has led us to develop a fourth multiphoton FLIM instrument which is based on our flexible design and includes adaptive optics developed using a spatial light modulator.

Multifocal Multiphoton FLIM: The most exciting development in my lab is currently the application of multi-beam multiphoton microscopy to parallelise fluorescence lifetime imaging using a newly developed CMOS SPAD camera system which incorporates pixel-by-pixel 50 ps timing for TCSPC. With Prof R. Henderson (Edinburgh) and Dr K. Suhling (Physics, KCL),we are appling a novel camera system to provide fast frame rate FLIM data for multiphoton microscopy. At current data rates, the imaging speed-up is modest (factor of 10 over current methodologies) but with firmware and hardware modifications this is expected to be improved to a factor 100. This technology forms the core of our MRC Next Generation Optical Imaging Programme.

Single molecule imaging and spectroscopy: We have developed two Total internal reflection super resolution imaging systems based on Nikon platforms with custom modifications for laser excitation and software. Both systems may be used for either ensemble measurements of cell membrane receptors or single-molecule imaging studies of protein-protein interaction. Following recent advances in the field of super-resolution microscopy we have added capability to undertake STORM and PALM experiments in two colours. Furthermore, In order to further our understanding of single-molecule spectroscopy, my group embarked on an exploration of single-molecule fluorescence lifetime spectroscopy based on TCSPC and the burst-integrated fluorescence lifetime technique (BiFL). A TCSPC-BiFL system was developed and tested using a number of fluorophores including quantum dots and fluorescent proteins.

 



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020 7848 6558
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Haemato-oncology
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Dr. Ramsay leads a research group focussing on translational research in cancer immunology. His research in the chronic lymphocytic leukaemia (CLL) and lymphoma field has characterised novel tumour cell-induced T-cell immune evasion mechanisms and translated bench science to clinical trials with immunotherapy (Ramsay et al JCI 2008)(Shanafelt and Ramsay et al Blood 2013)(Ramsay Br. J Haematol. 2013). This work includes pre-clinical defintion of CLL (Ramsay et al Blood 2012) and lymphoma (Ramsay et al Blood 2009) tumour cells co-opting multiple immune checkpoint (IC) molecules to suppress T-cell lytic immune synapse function ('adaptive immune resistance').
Current research focus: understanding and overcoming ‘microenvionmental immunosuppression’ in order to identify new targets for repairing anti-tumour immunity.
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+44(0) 207 848 5816
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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.
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020 7848 5803
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020 7848 5814
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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.
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78485888
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78485890
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Gene therapy-mediated immune rejection of cancer; cellular differentiation; molecular genetic analysis.
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+44(0)2078485902
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+44(0)2078485902
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The expertise of Prof Dazzi’s team focuses on the biology and clinical applications of cellular therapies for regenerative medicine. The central goal of regenerative medicine is to replace damaged or diseased tissue. Although traditionally associated with the transplantation of autologous or allogeneic stem cells, the data produced in recent years have led to a paradigm shit in regenerative medicine, according to which endogenous tissue repair can be promoted by controlling host inflammatory pathways. Along these lines, the main interest of the team is to understand the anti-inflammatory properties of mesenchymal stromal cells (MSC) and their interaction with myeloid accessory cells (monocytes and macrophages). Prof Dazzi has already initiated a national clinical programme based on MSC infusions to treat patients with immune mediated disorders, primarily graft-versus-host disease, but more recently autoimmune disease (Crohn’s) and solid organ transplantation.
The major players of the group are (in alphabetical order):
Dr Luigi Dolcetti (PhD) is looking into the transcriptomics and microRNA regulation of MSC-mediated immunosuppression with the ultimate view of identifying new molecules capable of triggering in situ MSC beneficial activity.
Dr Antonio Galleu (MD) aim is to discover the pathways which promote the activation of MSC therapeutic activity in the host. His results will identify not only the key mechanisms of this process, but also biomarkers to select the patients who are more likely to respond to MSC therapies.
Dr Cristina Trento (PhD) has discovered a key liaison between MSC and myeloid cells through which a complex network of immune regulation is generated. This loop, which regulates tissue homeostasis, is hijacked by leukaemia to protect malignant progenitors from the host immune attack and chemotherapy.
Alice Wang (MRes) and Dr Rehiana Ali (MD) are PhD students with an interest in the MSC activity on metabolism. Dr Ali is also coordinating a study on MSC treatment for multiple sclerosis.

The MSC clinical programme is currently being transferred from Imperial College (Prof Dazzi’s previous site) and taken to a new level with the use of different cell sources and bioengineering approaches. Two key persons are in charge: Dr Stephen Marley (PhD) who has successfully looked after the R&D aspects of MSC clinical programme in the last 3 years. He is equipped with long-standing research experience and with knowledge in biotech R&D. Steve has now been joined by Dr Ling Weng (PhD), the Lab Manager. Ling can exhibit an outstanding research record in transplantation immunobiology and a large experience in immune cell cultures.

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(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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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.
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020 7848 5839
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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.
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020 7848 5208
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020 7848 5902
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Molecular Haematology
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Clinical and molecular characterisation of red cell disorders; sickle cell disease and haemoglobinopathies.

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0203 299 3242
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Genetic mapping of measurable (quantitative) traits in humans; disease and trait inheritance in families, population-genetic basis of ethnic trait differences.

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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.
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020 7848 5443; 020 3299 1679
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020 7346 5178
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Research Oncology
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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.

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020 7188 9881
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02071883666
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In our Cancer Bioinformatics group, we are investigating the biology of invasive breast carcinomas mainly of the “triple negative” type, their precursor lesions, as well as the interplay with their surrounding immune /stromal microenvironment based on genomic and gene expression profile patterns.

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020 7188 1296
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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.
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020 7188 3027
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020 7188 9986
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Biobanking; translation studies relating to histopathological application; markers of proliferative activity.
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02071880874
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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.
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020 7188 4260
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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 late 2013 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

10. Goldstein R, Hanley C, Morris J, Chandra A, Chowdhury S, Maher J*, Burbridge S* (joint senior authors) (2011). Clinical investigation of the role of Interleukin-4 and Interleukin-13 in the evolution of Prostate Cancer. Cancers. 3, 4281-4293. http://www.mdpi.com/2072-6694/3/4/4281/pdf

11. Davies DM, Foster J, van der Stegen S, Parente ACP, Chiapero-Stanke L, Delinassios G, Burbridge SE, Kao V, Liu Z, Bosshard-Carter L, van Schalkwyk MCI, Box C, Eccles SA, Mather SJ, Wilkie S, Maher J (2012) Flexible targeting of ErbB dimers that drive tumorigenesis using genetically engineered T-cells. Molecular Medicine. 18(1): 565-76 http://www.ncbi.nlm.nih.gov/pubmed/22354215

12. Wilkie S, van Schalkwyk MCI, Hobbs S, Davies DM, van der Stegen SJC, Parente Pereira AC, Burbridge S, Box C, Eccles SA, Maher J (2012) Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. Journal of Clinical Immunology. 32(5): 1059-1070. http://www.ncbi.nlm.nih.gov/pubmed/22526592

13. Maher J (2012) Immunotherapy of malignant disease using chimeric antigen receptor-engrafted T-cells. ISRN Oncology. 2012: 278093. http://www.hindawi.com/isrn/oncology/2012/278093/

14. Leech J, Sharif-Paghaleh Ehsan, Maher J, Livieratos L, Lechler RI, Mullen G, Lombardi G, Smyth L (2013) Whole body imaging of adoptively transferred T cells using MRI, SPECT and PET techniques, with a focus on regulatory T cells. Clinical and Experimental Immunology. 172: 169-77. http://www.ncbi.nlm.nih.gov/pubmed/23574314

15. Maher J (2013) The role of the clinical immunology laboratory in disease monitoring. World Journal of Immunology. 3(2) 18-30. http://www.wjgnet.com/2219-2824/pdf/v3/i2/18.pdf

16. Parente-Pereira AC, Wilkie S, van der Stegen SJC, Davies DM, Maher J (2013) Use of retroviral-mediated gene transfer to deliver and test function of chimeric antigen receptors in human T-cells. Journal of Visualized Experiments. In press.

17. Parente-Pereira AC, Whilding L, Brewig N, van der Stegen SJC, Davies DM, Wilkie S, van Schalkwyk MCI, Ghaem-Maghami S, Maher J (2013) Synergistic chemo-immunotherapy of epithelial ovarian cancer using ErbB re-targeted T-cells combined with carboplatin. Journal of Immunology. In press.

18. Maher J, Adami AA (2013) Anti-tumor immunity – easy as 1 2 3 with monoclonal bispecific trifunctional antibodies? Cancer Research. In press.

Tel:
020 7188 1468
Fax:
020 7188 0919
Email:
Website:
Interests:
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
changes in O-linked glycosylation in breast cancer through their work on 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/KDM5B is a histone demethylase that is expressed in breast cancers and the developing mammary gland.  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, one of which appears to be regulated by COX-2.

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/KDM5B.

We are investigating how the changes in O-linked glycosylation affects the development of mammary cancer using model systems and how O-linked glycosylation affects breast cancer progression.  We are particularly interesting in studying how glycosylation helps to retain breast cancer cells within the bone marrow niche.
We are also looking at how particular tumour-associated glycoforms of MUC1 interact with immune cells to stimulate an immune response and suppress an immune response.

KDM5B binds to the estrogen receptor and so we are investigating the function of KDM5B and its role in estrogen receptor signalling. Moreover, KDM5B is highly expressed by HER-2 postive breast cancers so we are studying its role in response to Trastuzumab.

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
Fax:
020-718 80919
Email:
Website:
Interests:

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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Interests:
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 is Head of the Section of Research Oncology.

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.

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 has published over 200 peer-reviewed articles, and approaching 100 invited reviews and chapters on breast diseases in medical textbooks.
Tel:
020 7188 4260
Fax:
020 7188 0919
Email:
Website:
Interests:
Tel:
Fax:
Email:
Website:

ACADEMIC ENTRY REQUIREMENTS
General entry advice

Bachelor's degree with 2:1 honours degree in a relevant subject (or overseas equivalent). A 2:2 degree may be considered only where applicants also offer a Masters degree with Merit or above.

Applicants are strongly advised to contact potential supervisors prior completing the online application form. For further information please contact the Admissions Office Postgraduate (Health) team at pg-healthadmissions@kcl.ac.uk

NON ACADEMIC REQUIREMENTS
Enhanced criminal conviction check
Please note that research programmes within the School of Medicine may sometimes require a criminal conviction check depending on the particular topic/method of research.
Occupational Health clearance required?

APPLYING TO KING'S
To apply for graduate study at King's you will need to complete our graduate online application form. Applying online makes applying easier and quicker for you, and means we can receive your application faster and more securely.
King's does not normally accept paper copies of the graduate application form as applications must be made online. However, if you are unable to access the online graduate application form, please contact the relevant admissions/School Office at King's for advice.

APPLICATION PROCEDURE
Studentships may be advertised in publications such as findaphd.com. They are also posted on the College’s Health Schools Studentships website. Please note that most funding bodies will only support home/EU fees.

Self-funded applicants (through an awarded scholarship or private means) should submit a prospective application using the College online application form. It is recommended that self-funded applicants contact the Division and/or Research Section that they wish to apply to before making a formal application online.

If you are applying for a King's College London award such as the Graduate School International Research Awards, please make contact with the Divisional Manager in addition to submitting your application.
 
Shortlisted applicants will be interviewed by at least two academics from the Division. Proposed research projects must be approved before an offer to the student can be made (this is done via the completion of a Project Approval Form in collaboration with the proposed supervisors and is in addition to the online application).

PERSONAL STATEMENT & SUPPORTING INFORMATION
Please provide information on the research project you wish to undertake, your motivation to undertake postgraduate research and information about your research experience. If you are applying for a specific named project/studentship please include the reference number and project title. Self-funded applicants (through an awarded scholarship or private means) should provide details of how they will fund their studies and state the supervisor(s) to whom they wish to apply. As such it is advised that self-funded applicants contact the Division and/or Research Section that they wish to apply to before making a formal application online.

FUNDING
A small number of studentships, for specific projects, funded by external funding agencies such as the research councils (eg MRC), or charitable bodies are available each year (these are advertised on the Health Schools' Studentship page http://www.kcl.ac.uk/health/study/studentships/index.aspx and/or findaphd.com). These typically provide a stipend and the payment of tuition fees at the home/EU rate. Other applicants may be self-funded through a personal scholarship or private means. If you are self-funded please contact the Division or Research Section that you wish to apply to before submitting an online application.


Student profiles

Cancer Studies (Research Division) MPhil/PhD
I chose to do a PhD at King's because the Haematology Department has a very high reputation worldwide in the field of myelodysplastic syndromes and myeloid leukaemia research and several clinical trials and basic science researches are taking place within the department.
I am involved in a research project regarding the role of T lymphocytes in the pathogenesis of myelodysplasia sponsored by King's College Hospital Joint Research Committee. I am working in a very successful department which gives you good training, experience and opportunity to do valuable work.
My supervisors are highly experienced in haematological malignancies and have already conducted several successful projects. I have the opportunity to discuss my project with expert scientists and clinicians based within the department in a very friendly atmosphere, and it has helped me to complete a significant part of my project in the first year of study. I have weekly meetings with my supervisors and my progress is monitored regularly.
Thanks to scientific collaboration with other academic centres I have completed part of my project in the Cleveland Clinic Taussig Cancer Centre which is one of the top cancer centres in the USA. After completing my PhD, I would like to continue with clinical research and my academic career.