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Annual Report 2013 Onderzoekschool Oncologie Amsterdam Oncology Graduate School Amsterdam Annual Report 2013 Address Oncology Graduate School Amsterdam OOA VU medisch centrum Kamer PK 7Z 182 De Boelelaan 1117 1081 HV Amsterdam phone : 020-4443113 e-mail : [email protected] website : www.ooa-graduateschool.org Contents Preface 5 1 Board and organization 9 2 General report 13 3 Educational activities 19 4 PhD research program 25 5 Awards 49 Annex 1 Faculty and staff 53 Annex 2 International visitors 67 Annex 3 PhD theses completed 71 Annex 4 Scientific publications 81 Oncology Graduate School Amsterdam OOA preface Preface An important mission of the Oncology Graduate activities, including specialized training courses, School Amsterdam (Onderzoekschool Oncologie seminars and meet-the-expert sessions. Besides Amsterdam – OOA) is to organize the education in this, major effort is put into the organization of an basic and clinical cancer research of the graduate annual graduate student retreat. This retreat students in the Amsterdam region, and to ensure teaches skills in reporting, presenting and proper supervision and mentoring of graduate collaboration activities. students. The OOA graduate students are scientist- in-training who receive additional theoretical and This report presents the activities and scientific practical education on various subjects related to output of OOA in 2013. It includes detailed listings cancer. of our educational activities, such as training programs, and an overview of the scientific output, OOA is a joint venture of the medical faculties the including listings of PhD theses completed and VU University Medical Center (VUmc) and the scientific papers published throughout 2013. Academic Medical Center (AMC), of the VU University Amsterdam (Vrije Universiteit - VU) and the University of Amsterdam (Universiteit van Amsterdam- UvA), respectively, and the Netherlands Cancer Institute (Nederlands Kanker Instituut - NKI). These organizations strive for excellence in research and education in oncology, the realization of which is promoted by their participation in OOA. The OOA research program ranges from basic molecular biology to clinical bedside research. It includes, for instance, fundamental studies on cellular signal transduction and the control of gene Executive Directors, expression, but also clinical trials of new (combination) approaches and the development of Prof. dr. A.W. Griffioen (VUMC) new tools to evaluate the quality of life in cancer Prof. dr. T.K. Sixma and prof. dr. H. te Riele (NKI) patients. OOA organizes a range of educational Dr. M. Spaargaren (UvA) Preface - 7 8 - Preface Oncology Graduate School Amsterdam OOA board and organization 1 1. Board and organization Board Participating institutes Prof.dr. A. Berns, chairman VU University Amsterdam (VU)/ Prof.dr. S. Rodenhuis VU University Medical Center (VUmc) Prof.dr. C.J.L.M. Meijer Administrative center Prof.dr. P. Postmus Contact / secretariat: dr. E.M. Ruhé-Hoogervorst Prof.dr. C.E.E. Konings De Boelelaan 1117 Prof.dr. D.J. Richel 1081 HV Amsterdam phone : 020-4443113 fax : 020-4442964 Executive directors email : [email protected] Prof. dr. A.W. Griffioen, chairman University of Amsterdam (UvA)/ Prof. dr. T.K. Sixma till November 2013, prof. dr. Academic Medical Center (AMC) H. te Riele from November 2013 Meibergdreef 15 Dr. M. Spaargaren 1105 AZ Amsterdam phone : 020-5668502 fax : 020-5669165 Netherlands Cancer Institute (NKI) Contact / secretariat: Ms. P. Lagerweij Plesmanlaan 121 1066 CX Amsterdam phone : 020-512 6973 fax : 020-512 1944 email : [email protected] Faculty and staff The complete list of founding institutes’ faculty and staff involved in educational activities and research projects conducted by OOA is provided in Annex 1. Board and organization - 11 12 – Board and organization Oncology Graduate School Amsterdam OOA general report 2 2. General report Educational activities understanding of tumor development, progression and therapy resistance. Candidate markers are The OOA is a successful and large graduate school, tested for their ability to predict/detect cancer at with 507 PhD students, 117 faculty members an early stage. Disease profiling is being improved involved. It is the only Dutch research school using innovative research tools. Tools applied in specifically focusing on training in cancer research. research projects include high-throughput methods Monitoring of the quality of research in the for (epi)genetic, transcriptomic and proteomic different institutes is performed by local analyses. Examples are large tumor cohort screens committees at the participating institutes, e.g. a with CGH or expression arrays, gain-of-function research institute or board. genetic screens with retroviral cDNA expression The quality of the OOA is shown by its regular libraries, and loss-of-function genetic screens with accreditation by the Royal Netherlands Academy of RNA interference libraries. Quantitative mass Sciences regularly, currently for the period 2009- spectrometry is being used to search for proteins 2014. to distinguish the diseased and disease-free states. Mechanistic studies using e.g. structural biology The core activity of OOA is training PhD students in complement the functional studies. Advanced conducting cancer research. For this purpose, OOA mouse models or sophisticated xenotransplant has developed a high-quality curriculum. In 2013, models have been developed for the genetic OOA organized various graduate training courses dissection of cancer. At cellular level, processes and an Annual Graduate Student Retreat. like cell-cell communication, adhesion, migration, survival, proliferation and differentiation are all All courses were evaluated by means of being studied. Furthermore, the mechanisms of standardized evaluation procedures. In this way, therapy resistance and metastasis are being OOA carefully monitors the quality of its courses. investigated. Based on the outcome of these evaluations, the Viral oncogenesis projects focus on the role of training programs are being improved continuously. human papilloma viruses and Epstein-Barr virus in the development of human cancer, by using both in A detailed description of all training courses vitro models and clinically well-defined patient offered in 2013 is provided in chapter 3 of this tumor samples. Viral and host markers are being Annual Report. tested for their capability to assess the risk associated with the development of cancer. Research program Theme 2: Experimental clinical Research projects at OOA’s institutes can be research clustered under two main themes. The theme Improvements in clinical care in oncology are 'Experimental biology' covers 'Oncogenesis' and based on improved detection, development of 'Tumor cell biology' as the main lines of research. innovative therapies and personalized treatment The second main theme is 'Experimental clinical strategies. The emerging and rapidly growing fields research' and covers 'Diagnosis of cancer' and of molecular imaging and genomics are providing 'Prevention and therapy of cancer'. Chapter 4 new opportunities to study the biology of a provides listings of all individual PhD projects malignancy in individual patients and thus allowing conducted within these main themes. More for the development of highly valuable indicators detailed descriptions of these research programs for diagnosis and prediction of disease outcome. and their output are provided in the annual reports The development of the 70-gene breast cancer of the founding institutes. predictor at the NKI has led to the first FDA- approved diagnostic screen for breast cancer. Modern state-of-the-art techniques like MRI, Theme 1: Experimental biology SPECT, PET and PET/CT are enabling imaging The transformation of a normal cell into a methods with high precision and unique molecular malignant tumor cell requires multiple (epi)genetic and biological information at the tissue level. alterations affecting genes that control cellular (Molecular) reporter probes are being developed pathways. Studying the genes and proteins and evaluated. Highly developed mouse models are involved in these pathways results in better being used to follow drug sensitivity in several General report - 15 types of cancer and for developing clinical OOA has an excellent (inter)national status, as strategies for imaging. Targeted cancer therapy is demonstrated by the large number of research yet another research focus. Personalized therapy projects granted in open national and international should ensure optimal treatment benefits. Projects calls, including several of the prestigious new include (pre)clinical evaluations of the use of grants. The faculty is strongly represented in the neoadjuvant treatment or the application of new ‘vernieuwingsimpuls’, the Veni-Vidi-Vici molecular therapies and anti-angiogenic agents development grants for junior researchers and against novel targets in tumor and its environment. participates widely in CTMM projects and TI The pharmacological optimization of conventional Pharma projects as well as in numerous EU cytotoxic drugs is an important line of research, as integrated projects and networks of excellence. is the passage of drugs through the blood-brain Funding is also strongly supported by the Dutch barrier. Development of immunotherapies based on science foundation NWO and the cancer society, adoptive transfer and vaccination strategies are at KWF. the forefront of research. These, as well as novel targeted (anti-angiogenic) therapies and gene therapy
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