VUmc Cancer Center Amsterdam / VUmc Institute for Cancer & Immunology CCA/V-ICI

VUmc Cancer Center Amsterdam / VUmc Institute for Cancer & Immunology CCA/V-ICI Annual Report 2010

Address VUmc Cancer Center Amsterdam / VUmc Institute for Cancer & Immunology (CCA/V-ICI) VU University Medical Center CCA 3.36 De Boelelaan 1117 1081 HV Amsterdam The Netherlands phone: (31)20 4443113 e-mail: v-ici@vumc.nl website : www.vumc.nl/afdelingen/cca-v-ici 1

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List of contents List of contents 1. Preface 5 2. Description of CCA/V-ICI 7 3. Structure of CCA/V-ICI 9 4. SWOT analysis 11 5. International collaboration 13 6. Input CCA/V-ICI 17 7. Output CCA/V-ICI 19 8. The research programs of CCA/V-ICI 21 9. Scientific Research Committee 37 10. Training and education 47 Appendices 53 3

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1. Preface 1. Preface It is a great pleasure to present the 2010 annual report of CCA/V-ICI. The institute is really flourishing with an even rising production in scientific output, both quantitatively and qualitatively. In 2010, some important steps were made: the foci in patient care of VUmc: "zwaartepunten", were further defined. For CCA/V-ICI cancer and immunology in patient care go side by side with the researchprograms and further integration of care and research are very rapidly progressing. I wish you much pleasure in reading this report! Peter Huijgens, director 5

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2. Description of CCA/V-ICI 2. Description of CCA/V-ICI CCA/V-ICI is one of the five research institutes of the VU University Medical Center. CCA/V-ICI was created to integrate all research efforts in oncology and immunology in such a way that they strengthen themselves to reach well-defined, interconnected goals. Furthermore, CCA/V-ICI aims to create new facilities for fundamental and clinical research, both in terms of laboratory facilities, and technical equipment, and will stimulate cooperation. CCA/V-ICI is positioned horizontally in the structure of the VUMC, thus interfacing with the different divisions of clinical and pre-clinical departments. The CCA/V-ICI organization is built around the top researchers in oncology and immunology in the VUMC. They are the members of the executive board, advising the management board that heads the institute. A detailed description of the organization of CCA/V-ICI, together with the organization scheme is given in appendix 1. About 75% of all VUmc medical departments are involved in research focussed on oncology and/or immunology. Research is conducted within five well defined research themes. Furthermore, five tumour types and two immunological disorders have been selected to form the focus for ongoing research efforts during virtually every stage of the disease. These include colorectal cancer, lung cancer, head and neck cancer, haematological cancers, neuro-oncology, rheumatoid disease, coeliakie, contact dermatitis and inflammatory bowel disease. In these patient groups, comprehensive clinical and research programmes will be established in which clinical care and research are fully integrated. These range from early detection and diagnosis to treatment and palliative care. Furthermore, CCA/V-ICI has excellent research expertise on HPV-related tumors, esophagus cancer, prostate cancer, retinoblastomas,breast cancer, psoriasis, insulin allergy and autoimmune hepatitis. To ensure that all the clinicians and researchers within CCA/V-ICI remain highly qualified, a lifelong learning programme has been set up, starting with undergraduate (bio)medical students and continuing through Master s and PhD level to postgraduate/specialist training and beyond. Mission The mission of CCA/V-ICI is to coordinate, stimulate and facilitate: - top level fundamental, translational and patient related research in immunology and cancer, within the framework of a defined number of research themes - top level multidisciplinary patient care - creation of excellent facilities for research and patient care - training of (young) investigators to ensure excellent fundamental and clinical researchers - optimal training of health care workers - fundraising To this end the tasks of CCA/V-ICI are: - Development of long-term policy - Attuning the institutional policy and the policies of the participating (heads of) departments - Facilitation and coordination of oncology and immunology research - Quality control and stimulation of research by stimulating cross interfaces between departments, research groups and clusters - Training, supervision and assessment of graduate students in research - Organization of courses, national and international seminars, entrance examinations, publications, conferences and all that is necessary in this frame work - Facilitation of multidisciplinary patient care and early diagnosis - Facilitation of providing information to patients and their relatives - Facilitation of the development of cure/care pathways for oncological and immunological patients groups - Facilitation of research facilities - Quality control and stimulation of support systems for clinical research - Training of health care workers; a.o. in the medical curriculum, and post-academic education - Coordination of the funding of programs 7

2. Description of CCA/V-ICI CCA/V-ICI future plans CCA/V-ICI aims to take and hold a leading position in fundamental and patient related research in cancer and immunology and to improve curative and palliative patient care and to be an attractive partner for external partners. In particular CCA/V-ICI will focus on: Virus-induced oncogenesis and the role of cancer genes in frequently occurring sporadic and inherited tumors Development of cell based immunotherapy against cancer and new immunosuppressive methods in immunological diseases Classification of diseases and disease monitoring by molecular imaging, genomics and proteomics Introduction and evaluation of new therapeutic modalities, combining immunotherapeutical approaches, DNA technology and improving existing therapy methods Translational research: what benefit will the aforementioned focus points bring for the patients. Generation of improved knowledge about quality of life of childhood and adult patients with oncological and immune-mediated diseases and their families and conduction of high quality innovative translational research into developments and readily available new supportive care strategies. 8

3. Structure of CCA/V-ICI 3. Structure of CCA/V-ICI The research projects in CCA/V-ICI are grouped in programs headed by three to five program leaders who are responsible for the organization, the coordination and the quality of the program. The program leaders constitute the Executive Board of CCA/V-ICI that reports to the Management Board of CCA/V-ICI. Program 1: Oncogenesis Program 1 covers both basic and translational research and is divided into two subthemes: 1. Viral oncogenesis, progression and early diagnostics 2. Genetic predisposition and cancer genes Program 2: Immunopathogenesis The CCA/V-ICI program 2 covers both fundamental and pre-clinical research in which immunological processes underlying homeostasis control, in relation with inflammatory diseases and cancer form major topics of research. Program 2 is subdivided into three research lines: 1. Homeostasis control and Inflammation 2. Host-pathogen interaction 3. Tumor immunology and pre-clinical immune therapy Program 3: Disease profiling The CCA/V-ICI program 3 covers fundamental and translational research to identify new determinants for diagnosis, prognosis and tailored treatment for immunological and oncological diseases. Program 3 is subdivided in three disease oriented research lines: 1. Solid tumors 2. Hematological malignancies 3. Chronic inflammatory diseases Program 4: Innovative therapy The CCA/V-ICI program 4 encompasses translational research within the field of oncological and immune-mediated, non-oncological diseases. The program has been organized along four research lines: 1. Chemotherapy 2. Immunotherapy 3. Radiotherapy and surgery 4. Gene therapy Program 5: Quality of life The CCA/V-ICI program 5 encompasses research within the field of quality of life of childhood and adult patients with oncological and immune-mediated, non-oncological diseases. The program Quality of life addresses four main topics: 1. Patient and proxy reported outcome 2. Allied health services and lifestyle 3. Psycho-oncology 4. Palliative Care 9

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4. SWOT analysis 4. SWOT analysis Strengths: Strong clinical and fundamental research units in one institute with excellent translational research lines Excellent facilities Excellent teaching program, including strong masterprograms Flat organization, theme meetings and general meetings Coordinated project applications Outpatient facility Strong departments represented in all crucial committees A number of exceptional strong clinical departments nationwide and worldwide (Pathology, Otolaryngology/Head-Neck Surgery, Hematology, Medical Oncology) Weakness: Dispersion in therapy program Limited equipment budget Strong dependence of translational research on patient mix Opportunities: Development of more bench to bedside research lines Integration of immunological and cancer research to develop new immunotherapeutical approaches New imaging facility Cooperation with other research institutes in Amsterdam and the western part of the Netherlands Threats: Financial situation of university medical centers in the Netherlands Increasing focusing of VUMC towards patient care because of financial reasons 11

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5. International collaboration 5. International collaboration Investigator Prominent associates Ang CW K.A. Krogfelt, Statens Serum Institut, Copenhagen, Denmark Appelmelk BJ J. Nigou, Centre National de la Recherche Scientifique, Département, Mécanismes Moléculaires des Infections Mycobacteriennes, Institut de Pharmacologie et de Biologie Structurale, and Institut de Pharmacologie et de Biologie Structurale, Université detoulouse, Université Paul Sabatier (Toulouse III), Toulouse, France G. Besra, School of Biosciences, University of Birmingham, Edgbaston, United Kingdom D. Umetsu, Harvard Medical School, Boston, USA Beelen RHJ J. Loreiro/M. Lopez Cabrera, Insituto de Biologica, Moleculas Eladio Vinuela, Madrid, Spain M. Bohm/C. Aufricht, Medizinische Universitaet, Pediatric and Adolescent Medicine, Vienna, Austria P. Fabbrini, Instito Renal Medicine, Milan, Italy Bitter W Richard Losick, Harvard University, Cambridge, USA Boers M Prof P. Tugwell, Prof G. Wells, University of Ottawa, Ca Prof D. Felson, University of Boston, USA Prof P. Brooks, University of Brisbane, Australia Prof V. Strand, University of Stanford, USA Prof. J. Kirwan, University of Bristol, UK Prof, W. Maksymovich, University of Edmonton, Canada Prof. J. Blazenby, University of Bristol, UK Dr. R. Christensen, University of Copenhagen, Denmark Braakhuis BJM Dr P. Golusinsky, Poznan University of Medical Sciences, Poznan, Poland Brakenhoff RH Prof A Ferlito, Dept Surgical Sciences, University of Udine, Italy Prof F McCormick, Director Cancer Centre UCSF, USA Dr N Korokhov, Vector Logics Inc, Birmignham AL, USA Castelijns JA P. Galluzzi, A.Cerasi, Department of Neurosciences, Azienda Ospedaliera Universitaria Senese, Interdepartmental Center of Nuclear Magnetic Resonance, University of Siena, Siena, Italy. Gizewski ER, Forsting M, Department of Diagnostic and Interventional Neuroradiology, University Hospital, Essen, Germany. Brisse HJ, Department of Radiology, Institute Curie, Paris, France Maeder P, Pediatric Hematology Oncology Unit and Radiology Department Service de radiodiagnostic et de radiologie interventionnelle CHUV Centre Hospitalier Universitaire Vaudois University Hospital CHUV, Lausanne, Switzerland Cloos J A.D. Schimmer, Princess Margaret Hospital, Ontario Cancer Institute, Toronto, Canada de Gruijl TD Dr C.H. June, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Philadelphia, USA Dr D.T. Curiel, Division of human gene therapy, University of Alabama at Birmingham, Birmingham Alabama, USA de Winter JP Krystyna H. Chrzanowska, Department of Medical Genetics, The Children s Memorial Health Institute, Warsaw, Poland Weidong Wang, National Institute on Aging, Baltimore, USA Dorsman JC Antoine M. Snijders, Cancer Research Institute, Comprehensive Cancer, University of California, San Francisco, CA, USA Gibbs S Sens-it-iv consortium (30 international partners multiple publications), Multiple in Europe (www.sensitiv.eu), Europe Giovannetti E Prof. F. De Braud, European Institute of Oncology, Milano, Italy Prof. U. Boggi, University of Pisa, Italy Prof. Daniela Campani, Associate Professor of Pathology, University of Pisa, Pisa, Italy Prof. Federico Cappuzzo, head dept. Oncology, Livorno Civil Hospital, Carrara, Italy 13

5. International collaboration Investigator Prominent associates Prof. Armando Santoro, head dept. Oncology and Hematology, Humanitas Hospital, Milan, Italy Prof. A. Falcone, Dept. Oncology, University of Pisa, Pisa, Italy Prof. R. Rosell, Dept. Oncology, Barcelona, Spain Dr. F. Crea, Scuola di Studi Superiori S.Anna, Pisa, Italy Dr. M. Cantore, Dept. Oncology, Civic Hospital Carrara, Carrara, Italy Dr. Marco del Chiaro, Karolinska Institute, Stockholm, Sweden Dr. Leticia G Leon, Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO-AG), C/Astrofísico Francisco Sanchez Universidad de La Laguna, La Laguna, Spain R. Danesi, University of Pisa, Pisa, Italy Prof. Giuseppe Giaccone, Chief Medicine Oncology Branch, National Cancer Institute, Bethesda, USA. Dr. P.A. Zucali & Prof. Dr. A Santoro, Humanitas Hospital, Milan, Italy Prof Filippo Minutolo, Associate Professor of Medicinal Chemistry, University of Pisa, Pisa, Italy Dr. Carmelo Tibaldi, University of Livorno, Livorno, Italy Dr. N Funel, University of Pisa, Pisa, Italy Prof. Dr. Y. Assaraf, Technion-Israel, Institute of Technology University, Haifa, Israel Heideman DAM Dr. S. Franceschi, International Agency Research on Cancer (IARC), Lyon, France Dr. G. Clifford, International Agency Research on Cancer (IARC), Lyon, France Dr. R. Thomas and colleagues, Max Planck Institute for Neurological Research, Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, Cologne, Germany European Early Lung cancer (EUELC) Consortium: John K. Field, Roy Castle Lung Cancer Research Programme, Cancer Research Centre, University of Liverpool, Liverpool, United Kingdom; Christian Brambilla, Institut Albert Bonniot, Université Joseph Fourier, INSERM U823; Grenoble, France Jansen G Prof dr. Y.G. Assaraf, The Technion-Israel Institute of Technology, Haifa, Israel Jiménez C, Schaaij-Visser TB, Pham TV, Piersma SR, Wurdinger T, Peerdeman SM, Saydam O, and Stemmer-Rachamimov AO O. Senol, Harvard Medical School, Boston, USA Kirtschig G Prof. Dr. H Williams, Nottingham University, Nottingham, UK EADV task force Skin disease in pregnancy, EADV, last meeting at the EADV event in Gotheburg, Sweden Mebius R Meijer GA Ronen Alon, the Weizmann Institute of Science, Rehovot, Israel Steven Pals, AMC, dept Pathology, Amsterdam A.J. Habenicht, Institute for Vascular Medicine, Friedrich Schiller University of Jena, Germany Prof. E. Schröck, Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus der TU Dresden, Dresden, Germany Prof. J.G. Herman and Prof. S. Bayling, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA Prof. F Pontén, Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden Prof. P. Quirke and H. Grabsch, PhD, Academic Unit of Pathology, University of Leeds, United Kingdom Prof. D. Sidransky,The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America Prof. W. van Criekinge, OncoMethylome Sciences S.A, Liege, Belgium R.T. Cormier, University of Minnesota Medical School, Duluth, MN, USA Prof. G.Giaccone, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA K.H. Buetow PhD, Center for Biomedical Informatics and Information Technology National Cancer Institute, Bethesda, MD, USA Mooi WJ Prof. R.L. Barnhill, Université Paris VII, France Prof. M. Cook, Nuffield Health Guildhford Hospital, England Prof. L. Cerroni, University of Graz, Austria Prof. D.E. Elder, University of Pennsylvania, USA Prof. H. Kerl, University of Graz, Austria Prof. P.E. LeBoit, University of San Francisco, USA Prof M. Mihm, Harvard University, USA 14

5. International collaboration Investigator Prominent associates Prof. R. Scolyer, University of Sydney, Australia Prof. L. Cerroni, University of Sydney, Australia Prof. L. Cerroni, University of Graz, Austria Peters GJ Dr. R.A. Schwendener, University of Zürich, Zürich, Switserland Prof. Dr. H Schott, University of Tubingen, Tubingen, Germany prof. Dr. J Balzarini, Rega Instituut, KU Leuven, Leuven, Belgium Prof. Dr. O Fodstadt, Radium Hospital, Oslo, Norway Prof. Dr. S. Eriksson, Uppsala University, Uppsala, Sweden Dr. M. Sandvold, Clavis Pharma ASA, Oslo, Norway C. Calhau, University of Porto, Porto, Portugal I. Fichtner, Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany. Dr. J.M. Padron, Instituto Canario de Investigación del Cáncer (ICIC), Tenerife, Spain Dr. M Fukushima, Taiho Pharmacenticals, Tokushima, Japan Prof.dr. H. Schott, University of Tubingen, Germany Dr. C.M. Galmarini, PharmaMar, Madrid, Spain Prof. Alfredo Falcone, Head Department of Oncology, University of Pisa, Pisa, Italy Prof. Ugo Boggi, Full Professor of Surgery, University of Pisa, Pisa, Italy Prof. Daniela Campani, Associate Professor of Pathology, University of Pisa, Pisa, Italy Prof. Federico Cappuzzo, Head Department of Oncology, Livorno Civil Hospital, Livorno, Italy Dr. Maurizio Cantore, Head Department of Oncology, Carrara Civic Hospital, Carrara, Italy Prof. Filippo De Braud, Head Unit Oncology and New Drugs, European Institute of Oncology, Milan, Italy Dr. Marco Del Chiaro, Karolinska Institute, Stockholm, Sweden Dr. Leticia G Leon, Instituto Universitario de Bio-Organica Antonio Gonzalez (IUBO-AG), C/Astrofísico Francisco Sanchez Universidad de La Laguna, La Laguna, Spain R. Danesi, University of Pisa, Pisa, Italy Prof. Giuseppe Giaccone, Chief Medicine Oncology Branch, National Cancer Institute, Bethesda, USA. Dr. P.A. Zucali & Prof. Dr. A Santoro, Humanitas Hospital, Milan, Italy Prof Filippo Minutolo, Associate Professor of Medicinal Chemistry, University of Pisa, Pisa, Italy Dr. Carmelo Tibaldi, University of Livorno, Livorno, Italy Dr. N Funel, University of Pisa, Pisa, Italy Prof. Dr. Y. Assaraf, Technion-Israel, Institute of Technology University, Haifa, Israel Rustemeyer T Sens-it-iv consortium (30 international partners 1 publication), Multiple in Europe (www.sensitiv.eu), Europe Savelkoul PHM Nuno Pais, Roche Molecular Systems, Plesangton, USA Senan S D. Palma, London Regional Cancer Program, Ontario, Canada Kong (Spring) FM, University of Michigan Medical School; Ann Arbor, Michigan W.D. D Souza, University of Maryland School of Medicine, Baltimore, USA C. le Péchoux, Institut Gustave Roussy, Paris, France J.P. van Meerbeeck, University of Ghent, Ghent, Belgium G. Scagliotti, University of Turin, San Luigi Hospital, Turin, Italy U Nestle, Freiburg University Medical Center, Freiburg, Germany C. Faivre-Finn, The Christie, Manchester, United Kingdom S. Ishikura, National Cancer Center Hospital East, Kashiwa, Japan Slotman BJ D. Palma, London Regional Cancer Program, Ontario, Canada Sminia P Fedrigo C.A. Catholic University Rio Grande do Sul, Porte Alegro, Rio Grande do Sul, Brazil van Beusechem VW Prof. F. McCormick, UCSF Cancer Center, San Francisco, California, USA Dr. Z.B. Zhu, Gene Therapy Center, UAB, Birmingham, Alabama, USA van de Loosdrecht AA Dr. S.M. van Ham, Sanquin Research at CLB, Amsterdam Dr. T. van den Berg, Sanquin Research at CLB, Amsterdam Prof. Dr S. Ostrand-Rosenberg; Baltimore, USA Dr. M. Loken and D. Wells. HematoLogics Inc. Seattle USA 15

5. International collaboration Investigator Prominent associates European LeukemiaNet MDS working package 8 (implemanatation of flowcytometry in MDS) Dr. J. Janssen, Prof.dr. T. de Witte. UMCN, Nijmegen Dr. M. Raaijmakers, ErasmusMC, Rotterdam van den Elsen PJ K Kobayashi, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA M Villalba, Institut de Génétique Moléculaire de Montpellier, Unité Mixte de Recherche 5535, Centre National de Recherche Scientifique, Montpellier, France J. McClusky, Department of Microbiology & Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia van der Horst-Bruinsma IE ASAS- Society: internationaal samenwerkingsverband van reumatologen mbt spondylitis ankylopoetica van der Sar AM Dr. S. Bird, University of Aberdeen, Aberdeen, UK van der Waal I Meleti M, Unit of Oral Pathology and Medicine, Section of Odontostomatology, Department of ENT/Dental/Ophthalmological and Cervico-Facial Sciences, University of Parma, Italy R.A. Mendes, Department of Oral Surgery, Faculty of Dental Medicine, University of Porto, Porto, Portugal J.F.C. Carvalho, Department of Oral Surgery, Faculty of Dental Medicine, University of Porto, Porto, Portugal R.A. Mendes, Instituto Superior de Ciências da Saúde, Norte, Porto, Portugal. G. Warfvinge, Department of Pathology, Malmö, Sweden van Die I R. Geyer, Giessen University, Germany R.D. Cummings, Emory University Medical School, Atlanta, USA van Dongen GAMS Kiefer GE, Jurek P, Macrocyclics Inc, Dallas, Texas, USA van Egmond M Prof.dr. P. Kubes, University of Calgary, Calgary, Canada Prof.dr. J. Ivanyi, Kings College, London, UK van Furth AM Prof. dr. J. Schoeman, Tijgerberg Hospital, Cape Town, South-Africa van Furth AM and van der Kuip M Prof. D. Kirschner, Department of Microbiology and Immunology, Uiversity of Michigan, Ann Arbor, Michigan, USA van Kooyk Y Collaboration with the group of Dr. Eduardo Arranz (Mucosal Immunology Lab, Dept. of Paediatrics & Immunology-IBGM, University of Valladolid, Valladolid, Spain) on immunomodulation of gliadin-specific immune responses through C-type lectin receptor targeting. Resulted in the visit of a PhD student (Enrique Montalvillo) for two months (October-November, 2010) Verweij CL Prof. dr. P.h. De Jager, Harvard University, Boston, USA Prof. Dr. D.A. Hafler, Yale University, Rochester, USA Prof. dr. M. Holers/ Dr. K. Dean, University of Colorado, Denver, USA Prof. dr. M. Comabella/Prof. dr. X. Montalban,, University of Vall d Hebron,, Barcelona, Spain Wurdinger T Dr. Bakhos Tannous, Massachusetts General Hospital/Harvard Medical School, Boston/USA Ylstra B Prof. dr. Nick Gilbert, Univeristy of Edinburgh, Edinburgh, UK Prof. dr. Patricia Maciel, University Minho, Portugal Zweegman S M.Huizing, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA 16

6. Input CCA/V-ICI 6. Input CCA/V-ICI a. Acquisition per type of funding in euros Funding 2010 2009 2008 2007 Direct funding 8.109.439 6.927.240 6.605.989 6.665.874 Research funding 2.116.673 1.744.730 1.651.343 1.278.026 Contracts 5.596.577 4.830.820 4.865.624 3.177.712 Total 15.822689 13.502.790 13.122.956 11.121.613 As percentage: Funding 2010 2009 2008 2007 Direct funding 51,3% 51,3% 50,3% 59,9% Research funding 13,3% 12,9% 12,6% 11,5% Contracts 35,4% 35,8% 37,1% 28,6% Total 100% 100,0% 100,0% 100,0% b. Fte per type of funding For a full list of all scientific input, see appendix 2. Total fte (including PhD students) Program WP1 Fte WP2 fte WP3 fte WP4 fte Total fte 1. Oncogenesis 13,97 5,13 22,62 3,17 44,89 2. Immunopathogenesis 21,61 24,55 16,33 3,67 66,16 3. Disease profiling 15,78 5,50 14,85 5,50 41,63 4. Innovative therapy 23,89 2,89 27,84 13,40 68,02 5. Quality of life 2,2 1,51 3,24 2,42 9,37 Total 2010 77,45 39,58 84,88 28,16 230,07 Total staff 2009 70,63 37,32 80,53 24,22 212,70 Total staff 2008 68,31 34,90 65,21 19,58 188,00 Total staff 2007 75,24 28,60 55,78 18,91 178,53 17

6. Input CCA/V-ICI Total fte PhD students Program WP1 Fte WP2 fte WP3 fte WP4 fte Total fte 1. Oncogenesis 3,42 2,10 11,30 1,50 18,32 2. Immunopathogenesis 7,85 7,71 6,80 2,25 24,61 3. Disease profiling 6,38 2,30 9,15 3,90 21,73 4. Innovative therapy 4,40 1,81 18,10 7,61 31,92 5. Quality of life 0,95 0,61 2,24 1,42 5,22 Total 2010 23,00 14,53 47,59 16,68 101,80 Total 2009 20,24 14,40 44,41 15,79 94,84 Total 2008 10,69 23,87 16,16 29,25 79,97 Total 2007 13,55 21,45 16,79 29,25 81,04 Total fte (including PhD students) 30 25 20 15 10 program 1 program 2 program 3 program 4 program 5 5 0 WP1 WP2 WP3 WP4 c. Number of all newly started PhD projects in 2010 In 2010, 19 new PhD projects were started. For a full list of all newly started projects and PhD students, see appendix 3. 18

7. Output CCA/V-ICI 7. Output CCA/V-ICI a. Scientific output A full list of the scientific output can be found in appendix 4. Program WpR WpNR WP VP PP OCT DI 1. Oncogenesis 49 5 - - - - 6 2. Immunopathogenesis 128 9 2 1 5 1 14 3. Disease profiling 83 5 1 5 - - 5 4. Therapy 332 24 6 15 1 4 20 5. Quality of life 33 4 - - - - 2 Total 2010 625* 47 9 21 6 5 47 Total 2009 522 59 31 15 1 2 43 Total 2008 502 32 27 12 - - 32 Total 2007 473 34 33 16 - - 26 WpR: Scientific papers refereed (former WI, WN + LE) WpNR: Scientific papers non refereed (former WI*) WP: Scientific publications (book, book chapters, proceedings) (former WB, WBC, RA) VP: Professional publications PP: Popular publications OCT: Patents DI: Dissertations *Due to an intense search on the internet, the amount of scientific papers are significantly higher than the years before. b. Scientific quality Evaluation of peer-reviewed publications (Science Citation Index (SCI) journals) Program 5 4 3 2 1 A B C D 1. Oncogenesis 17 19 8 3 2 49 193 3,9 73,5 2. Immunopathogenesis 46 47 26 4 5 128 509 4,0 72,7 3. Disease profiling 39 21 12 6 5 83 332 4,0 72,3 4. Therapy 134 98 50 28 22 332 1290 3,9 69,9 5. Quality of life 6 14 11 2-33 123 3,7 60,6 Total 2010 242 199 107 43 34 625 2447 3,9 70,6 Total 2009 201 166 94 44 17 522 2056 3,9 70,3 Total 2008 145 157 68 58 19 447 1692 3,8 67,6 Total 2007 153 108 100 37 22 420 1592 3,8 62,1 Relation between scores and journal 5: SCI journal belonging to > 90th percentile (5 points) 4: SCI journal belonging to 75th 90th percentile (4 points) 3: SCI journal belonging to 50th - 75th percentile (3 points) 2: SCI journal belonging to 25th 50th percentile (2 points) 1: SCI journal from lowest quarter, publications in peer-reviewed journals without an Impact Factor (1 point) 19

7. Output CCA/V-ICI A: WI total B: Total points C: Average points D: Percentage of WI SCI journals in upper quartile (4 + 5) c. Indicators of esteem An overview of editorships, memberships, invited lectures, awards, grants obtained, organisation of congresses and news are outlined in appendix 5. d. Societal impact An overview of the Societal Impact of CCA/V-ICI is shown in appendix 6. e. Input/Output correlation Program Total fte Total WpR Average WpR/fte 2010 Average WpR/fte 2009 Average WpR/fte 2008 Average WpR/fte 2007 1. Oncogenesis 44,89 49 1,1 1,0 1,3 1,6 2. Immunopathogenesis 66,16 128 1,9 2,7 2,2 2,3 3. Disease profiling 41,63 83 2,0 2,6 4,1 2,3 4. Innovative therapy 68,02 332 4,9 2,6 2,2 2,7 5. Quality of life 9,37 33 3,5 6,4 - - Total 230,07 625 2,7 2,5 2,5 2,4 20

8. The research programs of CCA/V-ICI 8. The research programs of CCA/V-ICI A long-term policy is developed for the programs, covering their focus, the need for personnel and materials, their budgets and their development. These long-term plans constitute the basis of the long-term policy of CCA/V-ICI. Research projects are evaluated on their (intrinsic) qualities and on their potential to strengthen the program as a whole. The program leaders present such projects in the EB for advice upon which the Management Board decides to allow or not to allow the project into CCA/V-ICI. A list of all ongoing projects per program is shown in appendix 7. a. Description Program 1: Oncogenesis Program leaders: - Prof. R.H. Brakenhoff, PhD (Otolaryngology/Head-Neck Surgery) - Prof. H. Joenje, PhD (Clinical Genetics) - Prof. P.J.F. Snijders, PhD (Pathology) Program 1 covers both basic and translational research and is divided into three subthemes: 1. Viral oncogenesis 2. Cancer genomics 3. Genetic predisposition A major common objective of the research brought together in this program is to identify and characterize viral and non-viral cancer genes as well as genes responsible for inherited cancer predisposition. Their roles in oncogenic pathways are evaluated in models and clinical material. In addition, molecular markers are sought that may be utilized for a) screening for cancer and precancerous lesions, b) risk assessment of precancerous lesions, and c) cancer prevention. To this end an integrated bench to bedside approach is followed encompassing: 1) marker identification and clinical validation, 2) test development, validation and up-scaling by robotics, 3) risk group identification, 4) cost-effectiveness modelling, and 5) public acceptance studies. Screening studies are running for oral precancer, colorectal cancer and cervical cancer, in various risk groups, and often in the context of population-based screening trials. 1. Viral oncogenesis This subtheme focuses on the role of human papillomaviruses (HPVs) and Epstein Barr virus (EBV) in the development of human cancers, such as anogenital cancers, head and neck cancers, and lymphomas. Virus-induced oncogenic progression is investigated using both in vitro models and clinically well-defined patient material, and the genes involved in this process are identified and characterized. Viral and host markers are already being tested in screening and clinical trials for their capability to assess the risk of premalignant disease with an increased sensitivity and specificity compared to currently existing methods, and newly identified markers will be investigated likewise. 2. Cancer genomics Aimed at testing progression models for several human cancers, such as head and neck, lung, gastrointestinal, cervical and ovarian cancers, this subtheme uses wellcharacterized cohorts of patients and state-of-the art high-throughput methods for genetic, epigenetic, transcriptome and proteome analyses. Candidate cancer genes are identified, placed in their respective cancer pathways, and tested for their oncogenic capacity with the aid of in vitro models. Promising progression markers are evaluated in clinical studies. 3. Genetic predisposition In this subtheme understanding the molecular mechanisms of genome destabilization, as related to the occurrence of cancer, both familial and sporadic is studied. Attention is currently focusing on Fanconi anemia (FA), for which the pathway is being unravelled (13 FA genes known to date) and mouse models are being developed. It is recognized 21