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

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1 VUmc Cancer Center Amsterdam / VUmc Institute for Cancer & Immunology CCA/V-ICI Annual Report 2009

2 Address VUmc Cancer Center Amsterdam / VUmc Institute for Cancer & Immunology (CCA/V-ICI) VU University Medical Center CCA 3.36 De Boelelaan HV Amsterdam The Netherlands phone: (31) website : 1

3 2

4 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 International collaboration Input CCA/V-ICI Output CCA/V-ICI The research programs of CCA/V-ICI Scientific Research Committee Training and education 49 Appendices 55 3

5 List of contents 4

6 1. Preface 1. Preface It is a great pleasure to present the 2009 annual report of CCA/V-ICI. The institute is really flourishing with an even rising production in scientific output, both quantitatively and qualitatively. In 2009, some important steps were made: the institution of a fifth program: Quality of Life, which is a co program together with the EMGO research institute. Furthermore, patient groups were defined for which CCA/V-ICI offers excellent research programs. These definitions seems to make choices in the patient mixes for which VUmc is thé hospital to be if needs dictate so. Further progress in translational research will be enhanced by this process of aligning care and research efforts. I wish you much pleasure in reading this report! Peter Huijgens, director 5

7 1. Preface 6

8 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 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 and breast cancer. 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

9 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

10 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. In 2009 a new program was added. Program 5 encompasses research within the field of quality of life of childhood and adult patients with oncological and immune-mediated, non-oncological diseases. 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

11 3. Structure of CCA/V-ICI 10

12 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

13 4. SWOT analysis 12

14 5. International collaboration 5. International collaboration Investigator Prominent associates C.W. Ang, PhD K.A. Krogfelt, Statens Serum Institut, Copenhagen, Denmark U Gross, University of Gottingen, Gottingen, Germany D.G. Newell, Veterinary Laboratories Agency, New Haw, United Kingdom B.J. Appelmelk, PhD 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; H. Takata, Biochemical Research Laboratory, Ezaki Glico Co., Ltd, Nishiyodogawa-ku, Osaka, Japan N. Bovin, Carbohydrate Chemistry Laboratory, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia G. Besra, School of Biosciences, University of Birmingham, Edgbaston, United Kingdom G. Painter, Carbohydrate Chemistry Team, Industrial Research Limited, Lower Hutt 5040, New Zealand Prof. R.H.J. Beelen, PhD 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 I.V. Bijnsdorp, PhD and Prof. G.J. Peters. PhD R. Schwendener, Laboratory of Liposome Research, Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland H. Schott, Institute of Organic Chemistry, University of Tübingen, Tübingen, Germany, Fichtner, Experimental Pharmacology, Max Delbrück Center for Molecular Medicine, Berlin, Germany M. Fukushima, Tokushima Research Center, Taiho Pharmaceuticals Co., Ltd., Tokushima, Japan W. Bitter, PhD Roland Brosch, Institut Pasteur, Paris, France Richard Losick, Harvard University, Cambridge, USA Hans J Vogel, University of Calgary, Calgary, Canada Nico Gey van Pittius, University of Stellenbosch, Stellenbosch, South Africa R. Boellaard, PhD Various colleagues across Europe, EANM, European association of nuclear medicine, Europe L.Velasquez, Bristol Meyer Squib, BMS, USA L. Nogova, MPI Cologne, Germany Prof. M. Boers, PhD Prof P. Tugwell, Prof G. Wells: U of Ottawa, Ca. Prof D. Felson, U of Boston, USA. Prof P. Brooks, U of Brisbane, Au. Prof V. Strand, U of Stanford, USA. Prof. J. Kirwan, U of Bristol, UK. Prof, W. Maksymovich, U of Edmonton, Ca. Prof. R.H. Brakenhoff, PhD K Pantel, University Medcial Center Eppendorf, Hamburg/Germany J. de Haan, PhD dr. A. Limmer, Institute for Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany V. de Haas, PhD J. Grill, Institut Gustave Roussy, Paris, France J.P. de Winter, PhD Ruhikant Meetei, University of Cincinnati, Cincinnati, USA Lei Li, University of Texas M.D. Anderson Cancer Center, Houston, USA J.J. Garcia Vallejo, PhD Prof. H. Ploegh, Whitehead Institute, Boston, Massachussets (USA) S. Gibbs, PhD Sens-it-iv consortium (30 international partners multiple publications), Multiple in Europe (www.sensitiv.eu), Europe 13

15 5. International collaboration Investigator E. Giovanetti, PhD and Prof. G.J. Peters, PhD Prominent associates Prof. C. Calhau, University of Porto, Porto, Portugal Prof. R. Danesi, Dept. internal Medicine, University of Pisa, Pisa, Italy Prof. G. Giaccone, NIH, Washington, MD, USA Dr. Paolo Zucali, IRCCS Humanitas, Milano, Italy Dr. C. Tibaldi, Livorno Civil Hospital Dr. C. Ceresa, Bicocca University, Milano, Italy E. Giovannetti, PhD Prof. F De Braud, European Institute of Oncology, Milano, 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 Prof. A.W. Griffioen. PhD Prof dr. F. Poirrier, Institut Jussieu, Paris, France Prof dr. Z. Fayad, dr. W. Mulder, Mount Sinai School of Medicine, New York, USA dr. S. Memet, Insitut Pasteur, Paris, France D. Heideman, PhD Dr. W. Quint, DDL, Voorburg P.E. Castle, Dept of Cancer Epidemiology and genetics, National institute of health, Washington, USA E.L. Franco, Division of Cancer Epidemiology, Mc Gill University, Montreal, Canada G Ronco, Unit of Cancer Epidemiology, Centro per la prevenzione Oncologica, Turin Italy M. Arbyn, Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium and ECCG (European Cooperation on development and implementation of Cancer screening and prevention Guidelines), IARC, Lyon, France FX. Bosch, Servei d epidemilogia, institut Catala d Oncologia, Hospitalet del llobregat, Barcelona, Spain J. Cuzick, Queen Mary s School of Medicine and Dentistry and Cancer Research UK, London, UK J. Dillner, Department of Medical Microbiology University Hospital, Lund University, Malmö, Sweden G. Jansen, PhD Prof. Dr. M. Ratnam, Medical University of Ohio, Toledo (OH)/U.S.A. Prof Dr. A.L. Jackman, Institute of Cancer Research, London, UK G. Jansen, PhD, Prof. G.J. Peters, PhD Prof. Dr. Y. G. Assaraf, Technion University, Haifa, Israel C. Jimenez, PhD Prof Ole Jensen. Protein mass spectrometry group. Odense. Denmark Dr. Matthew Fitzgibbon, Fred Hutchinson Cancer Research Center, Seattle, USA Dr. L. Pasa-Tolic, Mass Spectrometry Facility, Pacific Northwest National Laboratory, USA Dr. Frode Berven, Proteomics Unit, University of Bergen, Bergen, Norway Dr. Simone Niclou, NorLux Neuro-Oncology Laboratory, Luxembourg Prof. S. Gammeltoft, Department of Clinical Biochemistry, Glostrup Hospital, Denmark Prof. dr. AL Burlingame, Mass Spectrometry Resource, University of California San Francisco, USA Dr. D. Gillooly (Invitrogen, Finland) Dr. M. Hornshaw (London, ThermoElectron) Dr. Matthias Glueckmann and Christie Hunter (Applied Biosystems) Dr Gisela Brunagel, Univ. Bonn, Germany Prof. G.J. Kaspers, MD, PhD Emelyana Pane, Universitas Kristen Indonesia, Djakarta, Indonesia Prof dr Max Mantik, Stefanus Gunawan, Universitas Sulawesi Utara, Manado, Indonesia D. Reinhardt, U. Creutzig, D. Webb, International BFM Study Group, Hannover, Germany G. Kirtschig, PhD Prof. Dr. H Williams, Nottingham University, Nottingham, UK Prof. Dr. F Wojnarowska, Churchill Hospital Oxford, Oxford, UK Prof. C.R. Leemans, MD, PhD Professor JL Lebebvre, Centre Oscar Lambret, Lille, France Prof. R. Mebius, PhD Guillermo Oliver, St. Jude Children s Hospital, Memphis, USA Andreas J. Habenicht, Institute for Vascular Medicine, Friedrisch Schiller University of Jena, Jena, Germany Michael Carroll, Institute Harvard Medical School, Boston, USA 14

16 5. International collaboration Investigator Prominent associates Dirk Elewaut, University Hospital, Ghent, Belgium Stefen martin, University medical Center, University of Freiburg, Freiburg, Germany Dirk Elewaut, University Hospital, Ghent, Belgium Troy Randall, University of Rochester, Rochester, NY 14642, USA Prof. G.A. Meijer, MD, PhD: 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 Prof. J.M. Middeldorp, MD, PhD Prof.dr. David Thorley-Lawson, Dept. Pathology, Tufts University, Boston, USA. Prof.dr. Lawrence Young and prof.dr. Martin Rowe, CRC Institute for Cancer studies, Univ. Birmingham, U.K. Prof.dr. Martin Allday, Dept Virology at St.Mary s hospital, Imperial college of London, London, UK Dr. Lifu HU and Prof.dr. Ingemar Ernberg, MTC, Karolinska University, Stockholm, Sweden. Prof.dr. Yi-Xin Zeng and prof. Musheg Zeng; Dept mol. oncology, Sun Yat-sen University, Guangzhou, China. Prof. Dr Denis Moss, prof.dr Rajiv Khanna: Queensland Institute for Medical Research, Brisbane, Australia. Prof.dr. Kenzo Takada, Dept. Tumor Biology, Hokkaido University, Sapporo, Japan. Prof.dr. Sofia M. Haryana, Gadjah Mada University, Medical School, Yogyakarta, Indonesia Prof.dr. Lori Frappier: Dept.molecular and medical genetics, University of Toronto, Canada. Dr. James Goeddert; Dept genetic and environmental epidemiology, National Cancer Institute, Frederic, USA Prof.dr Gavin Giovannoni, Dept. Neurol. Queen Mary Medical University, London, UK Prof. dr Nancy Raab-Traub, Dr. Margaret Gulley, Dept Pathology & Tumor Biology, UNC Chapel Hill, USA. Dr. Silvia de Sanjose, Institut Catala d Oncologia, Barcelona, Spain Prof.dr. G.Tsao: Dept. Pathology-Anatomy, University of Hong Kong. Dr. Pierre Busson, Inst. Gustave Roussy, Villejuif, France. Dr. Peter Amlot, CRC & Dept. Immunol. & Mol. Pathol., Royal Free Hospital, London, U.K. Dr. E. Weiderpass. Dept. Epidemiology, Karolinska Institute, Stockholm, Sweden. Dr. Erwan Piriou. SUNY Upstate Medical University, Syracuse, NY, USA Prof. G.J. Peters, PhD Dr. I. Fichtner, Max Delbruck Center, Berlin, Germany Dr.. Fukushima, Taiho Pharmaceuticals, Tokushima, Japan Dr. M.L. Sandvold, Clavis Pharma, Oslo, Norway Prof. Dr. J. Balzarini, Rega Institute, University of Leuven, Leuven, Belgium Dr.Y, Mayur, Medicinal Chemistry Division, College of Pharmacy, Raichur, India Dr. A.M. Burger, Wayne State University, Barbara Ann Karmanos Research Institute, Detroit, MI, USA Dr. F. Albertioni, Karolinska Institute, Stockholm, Sweden Prof. Dr. A. Paradiso, National Cancer Institute, Bari, Bari, Italy Prof. Dr. O. Fodstadt, Radium Hospital, Oslo, Oslo, Norway T.J. Postma, PhD Prof dr G Cavaletti, Universita di Milano, Bicocca, Monza, Italy J.C. Reijneveld, PhD A Rooney, University of Edinburgh, Edinburgh, United Kingdom R Grant, University of Edinburgh, Edinburgh, United Kingdom 15

17 5. International collaboration Investigator Prominent associates T. Rustemeyer, MD, PhD Prof. Dr. K.E. Andersen, Odense University, Odense, Denmark Prof. Dr. J.D. Johansen, Kopenhagen University, Kopenhagen, Denmark Prof. Dr. M. Bruze, Gotheburg University, Gotheburg, Sweden Prof. P.H.M. Savelkoul, PhD, Joe Rubin DVM, University of Sakatchewan, Saskatoon, Sakatchewan, Canada Prof. S. Senan, MD, PhD R Muirhead, The Beatson, West of Scotland Cancer Centre, Galsgow, Scotland G Hanna, Northern Ireland Cancer Centre, Northern Ireland, United Kingdom Le Péchoux C, Institut Gustave-Roussy, Villejuif, France DA Palma, University of British Columbia, Vancouver, British Columbia, Canada JR Pantarotto, Ottawa Hospital Cancer Centre, Ottawa, ON, Canada S Ishikura, Outreach Radiation Oncology and Physics Clinical Trials, National Cancer Center, Tokyo P. Sminia, PhD Prof. Dr. R. Mayer, MD, PhD, EBG MedAustron GmbH, Vienna, Austria R.D.M. Steenbergen, PhD Prof.dr. F. Rosl, DKFZ, Heidelberg, Germany Prof.dr. M. Esteller, Cancer Epigenetics and Biology Programme (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain Prof. M.J.B. Taphoorn. PhD M.J. van den Bent, on behalf of the EORTC Brain Tumour Group, EORTC Data Center, Brussels, Belgium R. Stupp, on behalf of the EORTC/NCI-Canada Brain Tumour Group, EORTC Data Center, Brussels, Belgium Bottomley, on behalf of the EORTC Quality of Life Department, EORTC Data Center, Brussels, Belgium I.E. van der Horst-Bruinsma, MD, PhD ASAS- Society: internationaal samenwerkingsverband van reumatologen mbt spondylitis ankylopoetica A.M. van der Sar, PhD Prof. Dr. M. Leptin, Institut für Genetik, Universität zu Köln, COLOGNE, Germany Prof. I. van der Waal, MD, PhD Department of Pathology, Complejo Hospitalario de Pontevedra, Pontevedra, Spain J. Seoane, naam instituut: Department of Pathology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain J. Cameselle-Tejeiro, Department of Pathology, Hospital do Meixoeiro, Vigo, Spain Department of Stomatology, School of Medicine and Dentistry, University of Santiago de Compostela, Santiago de Compostela, Spain Th. Lönig, Institut für Anatomie, Zentrum für Experimentelle Medizin, Universität Hamburg-Eppendorf, Hamburg, Germany I.M. van Die, PhD RD Cummings, Emory University Medical School, Atlanta, USA M. van Egmond, PhD JC Coffey, University College Dublin, Dublin, UK Prof. A.M. van Furth, MD, PhD Prof. dr. J. Schoeman, Tijgerberg Hospital, Cape Town, South-Africa Prof. A.J.P. Veerman, MD, PhD MN Sitaresmi, Universitas Gadjah Mada, Yogyakarta, Indonesia prof dr Sutaryo SpA-K, Universitas Gadjah Mada, Yogyakarta, Indonesia E. Supriyadi, Universitas Gadjah Mada, Yogyakarta, Indonesia PH Widjayanto, Universitas Gadjah Mada, Yogyakarta, Indonesia Emelyana Pane, Universitas Kristen Indonesia, Djakarta, Indonesia Prof dr Max Mantik, Stefanus Gunawan, Universitas Sulawesi Utara, Manado, Indonesia Prof. I.M. Verdonck-de Leeuw, PhD M DeBodt, Dept of Otolaryngology and Communication Disorders, University of Antwerp, Edegem, Belgium V Woisard, Dept of Otorhinolaryngology, Head and Neck Surgery, Larrey University Hospital of Toulouse, France T Nawka, Dept of Phoniatrics and Paedaudiology, University of Greifswald, Greifswald, Germany 16

18 5. International collaboration Investigator Prominent associates R Whurr, National Hospital for Neurology and Neurosurgery, London, Great Britain I Guimaraes, Speech Therapy Department Escola Superior de Saude do Alcoitao, Portugal EB Holmberg, Karolinska Institute, Dept of Logopedics & Phoniatrics, Karolinska University Hospital, Huddinge, Sweden CR Rosen, Dept of Otolaryngology-Head and Neck Surgery, University of Pittsburgh Voice Center, USA Schindler, Dept of Otorhinolaryngology and Ophthalmology, University of Milan, Italy Prof. C.L. Verweij, PhD Dr. M. Fero, Stanford University, Palo Alto, California, USA Prof. dr. S. Ibrahim, University of Rostock, Rostock, Germany Dr. S. Marsal, Hospital Val d Hebron, Barcelona, Spain Prof. dr. Ph. De jager, Harvard University, Boston, USA Prof. dr. M. Holers, University of Colorado, Denver, USA E. Bloemena Th Löning, K Röser - Institut für Anatomie, Zentrum für Experimentelle Medizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany S. Zweegman, MD, PhD M.Huizing, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA 17

19 5. International collaboration 18

20 6. Input CCA/V-ICI 6. Input CCA/V-ICI a. Acquisition per type of funding in euros Funding Direct funding Research funding Contracts Total As percentage: Funding Direct funding 51,3% 50,3% 59,9% Research funding 12,9% 12,6% 11,5% Contracts 35,8% 37,1% 28,6% Total 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 13,32 4,38 17,66 0,85 36,21 2. Immunopathogenesis 19,02 22,52 16,78 2,93 61,25 3. Disease profiling 11,10 5,78 17,01 3,75 37,64 4. Innovative therapy 25,74 4,64 26,98 15,99 73,35 5. Quality of life 1,45-2,10 0,70 4,25 Total staff ,63 37,32 80,53 24,22 212,70 Total staff ,31 34,90 65,21 19,58 188,00 Total staff ,24 28,60 55,78 18,91 178,53 Total fte PhD students Program WP1 Fte WP2 fte WP3 fte WP4 fte Total fte 1. Oncogenesis 4,45 1,55 6,68 0,75 13,43 2. Immunopathogenesis 7,35 6,75 9,01 1,10 24,21 3. Disease profiling 1,72 3,76 12,46 2,55 20,49 4. Innovative therapy 6,47 2,34 14,16 10,69 33,66 5. Quality of life 0,25-2,10 0,70 3,05 Total ,24 14,40 44,41 15,79 94,84 Total ,69 23,87 16,16 29,25 79,97 Total ,55 21,45 16,79 29,25 81,04 19

21 6. Input CCA/V-ICI 30 Total fte (including PhD students) program 1 program 2 program 3 program 4 program WP1 WP2 WP3 WP4 c. Number of all newly started PhD projects in 2009 In 2009, 24 new PhD projects were started. For a full list of all newly started projects and PhD students, see appendix 3. 20

22 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 Immunopathogenesis Disease profiling Therapy Quality of life Total Total Total 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 b. Scientific quality Evaluation of peer-reviewed publications (Science Citation Index (SCI) journals) Program A B C D 1. Oncogenesis ,2 71,1 2. Immunopathogenesis ,9 71,4 3. Disease profiling ,9 68,0 4. Therapy ,0 72,4 5. Quality of life ,7 55,6 Total ,9 70,3 Total ,8 67,6 Total ,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) A: WI total B: Total points C: Average points D: Percentage of WI SCI journals in upper quartile (4 + 5) 21

23 7. Output CCA/V-ICI The Hirsch-index in percentage of the scientific staff. This includes both clinical and non-clinical researchers. 30% 25% 20% 15% 10% % 0% c. Indicators of esteem An overview of editorships, memberships, invited lectures, awards, grants obtained, organisation of congresses en 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 2009 Average WpR/fte 2008 Average WpR/fte Oncogenesis 36, ,0 1,3 1,6 2. Immunopathogenesis 61, ,7 2,2 2,3 3. Disease profiling 37, ,6 4,1 2,3 4. Innovative therapy 73, ,6 2,2 2,7 5. Quality of life 4, ,4 - - Total 212, ,5 2,5 2,4 22

24 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 two subthemes: 1. Viral oncogenesis, progression and early diagnostics 2. Genetic predisposition and cancer genes A major common objective of the research brought together in this program is to identify and characterize viral and non-viral cancer genes and micrornas as well as genes and micrornas responsible for inherited cancer predisposition. Their roles in oncogenic pathways are functionally evaluated in experimental models as well as descriptively in clinical material. In addition, molecular markers and drug-able targets are sought that may be utilized for a) screening for cancer and precancerous lesions, b) risk assessment of precancerous lesions, c) cancer prevention, and d) cancer therapy. For the purpose of screening and risk assessment 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) costeffectiveness 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. Viral oncogenesis, progression and early diagnostics This subtheme focuses on the role of human papillomaviruses (HPVs) and Epstein Barr virus (EBV) in the development of human cancers, including 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. In line with the progression models for viral oncogenesis, also models are generated for head and neck cancer as well as gastrointestinal tumors. Viral and cellular markers are being or will be 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. Genetic predisposition and cancer genes Molecular mechanisms underlying the process of genomic destabilization, which is thought to be crucial for oncogenesis, are investigated in the context of both familial and sporadic cancer. Current focus is on the chromosomal instability disorders, in particular Fanconi anemia (FA; 15 genes so far identified) and the cohesinopathies (3 genes found), for which the molecular pathways are currently being unravelled and mouse models developed. It is recognized that a subset of sporadic cancers may possess a cellular FA or cohesion-deficient phenotype, which might be exploited through targeted therapeutic intervention based on synthetic lethality approaches. The possibility to sensitize (resistant) tumor cells by inhibition of the FA/BRCA pathway will also be explored. Three new research lines are being developed. First, the search for genes that contribute to genetic predisposition to breast/ovarian and colorectal cancer. Second, the elucidation of 23

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