2008 RAE Result: 67 per cent of research outputs from the Division were rated as world leading or internationally excellent
Research income: over £12.5 million in 2011-12
Current number of academic staff: 37
Current number of research students: PhD 48 FT, 21 PT
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.
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.
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.
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.
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.
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.
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.
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 firstname.lastname@example.org