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

Transcription

1 VUmc Cancer Center Amsterdam / VUmc Institute for Cancer & Immunology CCA/V-ICI Annual Report 2007

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) v-ici@vumc.nl website : 1

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4 Contents 1. Introduction 5 2. Organization of CCA/V-ICI Research programs & running projects 3.1 Program 1: Oncogenesis Program 2: Immunopathogenesis Program 3: Disease profiling Program 4: Therapy Input and output data 4.1 Scientific staff Publications Oncogenesis Immunopathogenesis Disease profiling Therapy Evaluation of input and output data Summary of input data Summary of output data Input/ Output correlation Disciplinary treatment program 5.1 Early diagnostics and hereditary predisposition Imaging Research to new therapies Psychosocial care, palliative care and supportive care Matrix analysis of clinical clusters versus tumor types Education 6.1 CCA/V-ICI program 6: Training and Education Graduate profile for medical students Masters for biomedical students PhD student program CCA/V-ICI evening lectures Scientific committee (CWO) 7.1 CWO: Clinical protocols CWO: Research projects / grant proposals CWO-DEC: Animal related protocols Indicators of esteem 8.1 (Inter)national collaboration Memberships of editorial boards (Inter)national functions Lectures Awards Grants obtained in

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6 1. Introduction CCA/V-ICI is one of the 5 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. CCA/V-ICI 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 chapter 2. The mission of CCA/V-ICI 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 programs training of young investigators to achieve excellence in fundamental and clinical research To this end the tasks of CCA/V-ICI are: facilitation and coordination of scientific oncology and immunology research quality control and stimulation of research conducted in joint departments, research groups and clusters development of long-term research strategies attuning the institutional policy and the policies of the participating (heads of) departments training, supervision and assessment of graduate students within the institute organization of courses, national and international seminars, entrance examinations, publications, conferences and other activities that are relevant for achieving the above goals The programs 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 (EB) of CCA/V-ICI that reports to the director and vice-director(s) of CCA/V-ICI. A long-term policy is developed for the programs, covering the need for personnel and materials, their budgets and their development. An indication is also given as to the focus on research lines. These long-term plans constitute the basis of the long-term policy of CCA/V-ICI. Research projects are evaluated by the program leaders on their (intrinsic) qualities and also on their potential to strengthen the program as a whole. The Scientific Research Committee (CWO) is responsible for the scientific input on protocols and research projects, which guarantees high quality standard. The programs stimulate their mutual coherence in the joined organization of monthly research evenings for all CCA/V-ICI participants. The programs have been chosen in order to enable optimal interaction between fundamental and clinical research (translation). 5

7 The programs are: 1. Oncogenesis - Viral oncogenesis - Cancer genomics - Genetic predisposition 2. Immunopathogenesis - Homeostasis control - Inflammation - Host-pathogen interaction - Tumor immunology and pre-clinical immune therapy 3. Disease profiling - Solid tumors - Hematological malignancies - Immunological diseases 4. Therapy - Chemotherapy - Immune therapy - Radiotherapy and surgery - Gene therapy - Quality of life 5. Multidisciplinary treatment program - Early diagnostics and hereditary predisposition - Imaging - Research for new therapies - Psychosocial, palliative and supportive care 6. Training and education In programs 1-5 the focus is on specified types of oncological and immunological malignancies for which bench to bedside expertise is present in a substantial group of fundamental and clinical researchers. The specific types of oncological and immunological malignancies are: Oncological malignancies or tumortypes: - Lung cancer - Colorectal cancer - Head and neck cancer - Prostate cancer - Brain tumor - Hematological malignancies - HPV related tumors - Hereditary tumors Immunological diseases: - Rheumatoid arthritis - Inflammatory Bowel Disease - Coeliac Disease Training and education for all personnel involved in CCA/V-ICI and for clinical postgraduate around the country is organised by the training and education program 6. Programs 1-4, their aims and perspectives as well as the projects they include, are described in chapter 3. In chapter 4 all the input and output data of the research programs 1-4 are summarized. Program 5 is described in chapter 5 and program 6 is described in chapter 6. 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 6

8 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. Through the concerted efforts of the programs with help by frequent program meetings and the monthly organised evening lectures these aims are well within reach of CCA/V-ICI. Careful selection of new projects, together with personnel, will be the main instrument to reinforce the research programs in the future. Education Within CCA/V-ICI there is a separate program for the education objectives, Program 6: Training and Education. Performing high quality research and patient care is an important goal of CCA/V-ICI. To this end, it is essential to train and to pass on knowledge to students, (young) researchers, technicians as well as to clinicians and care professionals. This educational path includes lectures, workshops, tutorials, practical training and clinical demonstrations. See chapter 6 for more details. In order to ensure highly qualified professionals in the future, it is essential to provide a well defined educational program starting already at medical and biomedical undergraduate students. CCA/V-ICI is involved in a high number of theoretical and practical courses during the bachelor as well as master phase. Furthermore, a high number of training positions are available at our laboratories. For medical students CCA/V-ICI organizes both an Oncology and an Immunology graduation profile. Furthermore, for the top medical students CCA/V-ICI is providing a Honours Program in Oncology and Immunology. In the General Master Biomedical Sciences CCA/V-ICI organizes the differentiation Immunology. For biomedical students a specific TOP-Master Oncology is available, which is aimed at the training of students for a research function in an oncological research institute. PhD students follow various theoretical and practical courses, most of them organized by the graduate schools in which CCA/V-ICI participate, such as the Oncology Graduate School Amsterdam (Oncologie onderzoeksschool Amsterdam -OOA) and Amsterdam Leiden Institute for Immunology (ALIFI). Monthly CCA/V-ICI lectures are organized in which the program/project leaders of the 4 research programs of CCA/V-ICI are actively involved. These lectures are aimed at achieving more integration of the research performed in the 4 different research programs and for education purposes for researchers in CCA/V-ICI. Postgraduate Education for (care) professionals is organized by the individual departments involved in CCA/V-ICI. In the future these and new activities will be organized together with CCA/V-ICI. One of the first initiatives will be a PET CT training center. Overview 2007 In 2007 a total of 76 clinical protocols were evaluated, with specific attention to the quality and feasibility of the proposed protocol, and all of them were approved. In addition, the Scientific Research Committee (CWO) evaluated a total of 119 research projects/grant proposals in A list of these protocols and projects can be found in chapter 7. This year the Chris Meijer Award, a yearly award given by CCA/V-ICI, for PhD students with a specific scientific achievement. was obtained by Sandra van Vliet. More information about awards can be found in chapter 8. 7

9 All publications are listed in chapter 4. Below, the 5 key publications per program are listed (x /y): after publications, x: quartile score (1-5), y: impact factor of journal Program 1 Bulkmans NW, Berkhof J, Rozendaal L, van Kemenade FJ, Boeke AJ, Bulk S, Voorhorst FJ, Verheijen RHM, van Groningen K, Boon ME, Ruitinga W, van Ballegooijen M, Snijders PJF, Meijer CJLM. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet 2007; 370(9601): (5 / 25.8) Dorsman JC, Levitus M, Rockx D, Rooimans MA, Oostra AB, Haitjema A, Bakker ST, Steltenpool J, Schuler D, Mohan S, Schindler D, Arwert F, Pals G, Mathew CG, Waisfisz Q, de Winter JP, Joenje H. Identification of the Fanconi anemia complementation group I gene, FANCI. Cell Oncol 2007; 29(3): (4 / 2.979) Heideman DAM, Waterboer T, Pawlita M, is-van DP, Nindl I, Leijte JA, Bonfrer JM, Horenblas S, Meijer CJLM, Snijders PJF. Human papillomavirus-16 is the predominant type etiologically involved in penile squamous cell carcinoma. J Clin Oncol 2007; 25(29): (5 / ) Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H, de Winter JP. Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat Genet 2007; 39(2): (5 / ) Vekony H, Ylstra B, Wilting SM, Meijer GA, van de Wiel MA, Leemans CR, van der Waal I, Bloemena E. DNA copy number gains at loci of growth factors and their receptors in salivary gland adenoid cystic carcinoma. Clin Cancer Res 2007; 13(11): (4 / 6.177) Program 2 Abdallah AM, Gey van Pittius NC, Champion PA, Cox J, Luirink J, Vandenbroucke-Grauls CMJE, Appelmelk BJ, Bitter W. Type VII secretion--mycobacteria show the way. Nat Rev Microbiol 2007; 5(11): (5 / ) Al-Toma A, Visser OJ, van Roessel HM, von Blomberg BME, Verbeek WHM, Scholten PE, Ossenkoppele GJ, Huijgens PC, Mulder CJ. Autologous hematopoietic stem cell transplantation in refractory celiac disease with aberrant T cells. Blood 2007; 109(5): (5 / 10.37) de Witte L, Nabatov AA, Pion M, Fluitsma D, de Jong MAWP, de Gruijl TD, Piguet V, van Kooyk Y, Geijtenbeek TBH. Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat Med 2007; 13(3): (5 / ) Gringhuis SI, den Dunnen JT, Litjens M, van Het HB, van Kooyk Y, Geijtenbeek TBH. C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB. Immunity 2007; 26(5): (5 / ) Molling JW, Langius JA, Langendijk JA, Leemans CR, Bontkes HJ, van der Vliet HJ, von Blomberg BME, Scheper RJ, van den Eertwegh AJM. Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma. J Clin Oncol 2007; 25(7): (5 / ) Program 3 Bulkmans NW, Berkhof J, Rozendaal L, van Kemenade FJ, Boeke AJ, Bulk S, Voorhorst FJ, Verheijen RHM, van Groningen K, Boon ME, Ruitinga W, van Ballegooijen M, Snijders PJF, Meijer CJLM. Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year follow-up of a randomised controlled implementation trial. Lancet 2007; 370(9601): (5 / 25.8) Hadithi M, von Blomberg BME, Crusius JBA, Bloemena E, Kostense PJ, Meijer JW, Mulder CJ, Stehouwer CD, Pena AS. Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Ann Intern Med 2007; 147(5): (5 / 14.78) Hermsen BB, von Mensdorff-Pouilly S, Berkhof J, van Diest PJ, Gille JJ, Menko FH, Blankenstein MA, Kenemans P, Verheijen RHM. Serum CA-125 in relation to adnexal dysplasia and cancer in women at hereditary high risk of ovarian cancer. J Clin Oncol 2007; 25(11): (5 / ) Hess CJ, Berkhof J, Denkers F, Ossenkoppele GJ, Schouten JP, Oudejans JJ, Waisfisz Q, Schuurhuis GJ. Activated intrinsic apoptosis pathway is a key related prognostic parameter in acute myeloid leukemia. J Clin Oncol 2007; 25(10): (5 / ) van der Pouw-Kraan TCM, Wijbrandts CA, van Baarsen LGM, Voskuyl AE, Rustenburg F, Baggen JM, Ibrahim SM, Fero M, Dijkmans BAC, Tak PP, Verweij CL. Rheumatoid arthritis subtypes 8

10 identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann Rheum Dis 2007; 66(8): (5 / 5.767) Program 4 Barlési F, Giaccone G, Gallegos-Ruiz MI, Loundou A, Span SW, Lefesvre P, Kruyt FA, Rodriguez JA. Global histone modifications predict prognosis of resected non small-cell lung cancer. J Clin Oncol Oct 1;25(28): (5/13.598) Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Peeters AJ, de Jonge-Bok JM, Mallée C, de Beus WM, de Sonnaville PB, Ewals JA, Breedveld FC, Dijkmans BA. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med 2007; 146(6): (5 / 14.78) Senan S, Haasbeek NJ, Smit EF, Lagerwaard FJ. Stereotactic radiotherapy for centrally located early-stage lung tumors. J Clin Oncol 2007; 25(4): 464 (5 / ) Slotman BJ, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus PE, Collette L, Musat E, Senan S. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007; 357(7): (5 / ) van Rhenen A, van Dongen GAMS, Kelder A, Rombouts EJ, Feller N, Moshaver B, Stigter-van Walsum M, Zweegman S, Ossenkoppele GJ, Schuurhuis GJ. The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood 2007; 110(7): (5 / 10.37) In 2007 several grants were obtained from various origin. Among industries several foundations like EU, Nederlandse Brandwonden Stichting, Smartmix, Top Institute Pharma, NWO, CCA, KWF, ZonMw and FP6 grants were obtained. In chapter 8 all indicators of esteem are given, like national and international collaborations and functions, memberships of editorial boards, grants and awards obtained and lectures that were given. 9

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12 2. Organization of CCA/V-ICI Board VUmc Management Board CCA / V-ICI External Advisory Board Internal Advisory Board Executive Board 1. Oncogenesis 2. Immunopathogenesis 3. Disease profiling 4. Therapy Scientific Research Committee 5. Multidisciplinary cancer treatment programs Staff 6. Training and education Management Board (MB) The two directors mutually replace each other, in chairing the MB. The deputy director of V-ICI replaces the director of V-ICI in and externally. The director of CCA coordinates the efforts for improvement of multidisciplinary cancer patient care and is responsible for the communication with the CCA fundraising institutions. The tasks of the director of CCA/V-ICI are described in the Management Regulation of the VUmc. Three senior board assistants, three junior board assistants and a secretary assist the MB. The MB meets every week. Management Board members: Prof. P.C. Huijgens, MD, PhD, director of V-ICI W.R. Gerritsen, MD, PhD, director of CCA Prof. G. Kraal, PhD, deputy director of V-ICI Prof. C.R.Leemans, MD, PhD, chairman of the internal advisory Board Staff: J.H. Buijs (junior board assistant) J.M. van Diemen-Markx (junior board assistant) Y.M. Duiker (junior board assistant) P. Keblusek, PhD, (senior board assistant)(till ) G.K. Kuipers, PhD (senior board assistant)(from ) G. La Rivière, PhD (senior board assistant)(from ) E.M. Ruhé-Hoogervorst, PhD (senior board assistant)(from ) S. Ruland-Adank (senior board assistant)(from till ) Internal Advisory Board: The members of the internal advisory board consist of 5 to 9 heads of departments involved in cancer and immunology within the VUMC. The chairman is member of the MB. The board meets at least every 6 months. 11

13 Internal Advisory Board members: Prof. C.R. Leemans, MD, PhD (Chair) Prof. M.A. Blankenstein, PhD Prof. B.A.C. Dijkmans, MD, PhD Prof. C.D. Dijkstra, MD, PhD Prof. C.J.L.M. Meijer, MD, PhD Prof. E.J.. Meijers-Heijboer, PhD (from ) Prof. B.J. Slotman, MD, PhD Prof. E.F. Smit, MD, PhD (from ) E.M. Ruhé-Hoogervorst, PhD (secretary)(from ) S. Ruland-Adank (secretary)(from till Education Committee The education committee advises about the organization and quality of graduate students training and supervises the progress of the graduate research performed by CCA/V-ICI graduate students. More in detail the education committee, by means of subgroups, organizes and advises about training in the framework of the: - oncology profile - immunology profile - masters education in oncology - masters education in immunology - graduate students education (OOA) Each of these five subgroups is composed of the main teachers within the education involved. The education committee are the program leaders of Program 6 Training and Education (see Chapter 5). The education committee gives asked and unasked advice about the quality and quality maintenance of education within CCA/V-ICI. The education committee meets at least three times a year. Education committee (CO) members: Prof. R.H.J. Beelen, PhD P. Keblusek, PhD, secretary (till ) Prof. C.R. Leemans, MD, PhD, chairman Prof. G.A. Meijer, MD, PhD R.A. Puras, PhD E.M. Ruhé-Hoogervorst, PhD, secretary (from ) Subgroups: Oncology profile committee members: B.J.M. Braakhuis, MD, PhD Prof. E. Boven, MD, PhD P. Keblusek, PhD, profile coordinator (till ) A.A. van de Loosdrecht, MD, PhD Prof. G.A. Meijer, MD, PhD E.M. Ruhé-Hoogervorst, PhD, profile coordinator (from ) Immunology profile committee members: B.J. Appelmelk, PhD M. van Agtmael, PhD B.M.E. von Blomberg, PhD I. van der Horst, PhD Prof. G. Kraal, PhD G.K. Kuipers, PhD, profile coordinator (from ) S. Ruland-Adank, profile coordinator (from till ) M.W.J. Schreurs, PhD Coordinator of the Master Oncology R.A. Puras, PhD 12

14 Programme committee Master s Oncology Prof. G.A. Meijer, MD, PhD, chairman P.J.F. Snijders, PhD, vice-chairman Turksma, student master Oncology, member Oudehand, student master Oncology, member R.A. Puras, PhD, programme coordinator, secretary Prof. R.H.A. Beelen, PhD, advisor Prof. J. Lankelma, PhD, advisor Prof. G.J. Peters, PhD, advisor Prof. R.J. Scheper, PhD, MD, advisor Zelda Euler, student master Oncology, advisor Thijs de Gunst, student master Oncology, advisor Board of examiners Master Oncology Prof. G.J. Peters, MD, PhD, chairman Prof. R.H.J. Beelen, PhD, vice-chairman Prof. R.J. Scheper, MD, PhD, member R.A. Puras, PhD, programme coordinator, secretary Coordinator of the Master Immunology Prof. Y. van Kooyk, PhD Board of examiners Biomedical Science FALW (including differentiation master immunology) B.M. Bakker, PhD Prof. R.H. J Beelen, PhD, chairman C. Zonneveld, PhD, vice-chairman L van den Grint, PhD P. de Boer, PhD, secretary Directorate OOA (Oncology Graduate School Amsterdam) Prof. G.A. Meijer, MD, PhD, chairman (VUmc) S. Boonen (NKI) Y.E. Donselaar, PhD (AMC) Prof. J.P. Medema, PhD (AMC) E.M. Ruhé-Hoogervorst, PhD, secretary (VUmc) Prof. T. Sixma, PhD (NKI) M.K. van der Velde (NKI) ALIFI PhD committee (Amsterdam Leiden Institute For Immunology) Prof. R.E. Mebius, PhD (VUmc-CCA/V-ICI) Prof. H. Schuitemaker, PhD (Sanquin) Prof. R.A.W. van Lier, PhD (AMC) Executive Board (EB) The Executive Board of CCA/V-ICI consists of the program leaders. The EB meets every 2 months together with the MB, chaired by one of the MB directors. The EB advises the MB about: Research projects Long-term policy with respect to personnel and materials First money stream graduate students Allocation of equipment for research of > Patient care projects Clinical and translational research Education Fundraising for cancer research, care and education Early diagnostics All matters concerning CCA/V-ICI whether on request or not The complete EB convenes regularly to discuss the long term policy of CCA/V-ICI. 13

15 Executive Board members: Program 1: Oncogenesis: Prof. R.H. Brakenhoff, PhD Prof. H. Joenje, PhD Prof. P.J.F. Snijders, PhD Program 2: Immunopathogenesis: Prof. R.H.J. Beelen, PhD E. Hooijberg, PhD Prof. Y. van Kooyk, PhD Prof. R. Mebius, PhD Program 3: Disease profiling: Prof. G.A.M.S. van Dongen, PhD Prof. O.S. Hoekstra, MD, PhD C. Jimenez, PhD Prof. G.A. Meijer, MD, PhD Prof. C.L. Verweij, PhD Program 4: Therapy: Prof. B.A.C. Dijkmans, MD, PhD Prof. G.J. Ossenkoppele, MD, PhD Prof. G.J. Peters, PhD Prof. S. Senan, MD, PhD Program 5: Multidisciplinary cancer treatment programs: W.R. Gerritsen, MD, PhD Program 6: Training and education: Prof. C.R. Leemans, MD, PhD Prof. R.H.J. Beelen, PhD Prof. G.A. Meijer, MD, PhD (director OOA) R.A. Puras, PhD E.M. Ruhé-Hoogervorst, PhD Heads of departments involved in CCA/V-ICI: Prof. B.L.H. Bemelmans, MD, PhD - Urology Prof. M.A. Blankenstein, PhD - Clinical chemistry Prof. P.T. Cohen-Kettenis, PhD - Medical Psychology Prof. S.A. Danner, MD, PhD Internal medicine Prof. S. Loer, MD, PhD - Anesthesiology Prof. B.A.C. Dijkmans, MD, PhD - Rheumatology Prof. C.D. Dijkstra, PhD - Molecular Celbiology and Immunology Prof. P.C. Huijgens, MD, PhD, a.i. - Medical Oncology Prof. J.J. Heimans, MD, PhD - Neurology Prof. P.C. Huijgens, MD, PhD Hematology Prof. A.A. Lammertsma, MD, PhD - Nuclear Medicine Prof. C.R. Leemans, MD, PhD Otolaryngology/Head and Neck Surgery Prof. C. van Kuijk, MD, PhD - Radiology Prof. C.J.L.M. Meijer, MD, PhD Pathology Prof. E.J. Meijers-Heijboer, PhD - Clinical genetics and antropogenetics Prof. C.J.J. Mulder, MD, PhD Gastro-enterology and hepatology Prof. P.E. Postmus, MD, PhD - Pulmonology Prof. J.A. Rauwerda, MD, PhD - Surgery Prof. P.J. Ringens, MD, PhD Ophthalmonoly B.J. van Royen (a.i.), MD, PhD - Orthopaedics Prof. J.J. Roord, MD, PhD - Paediatrics Prof. B.J. Slotman, MD, PhD - Radiotherapy Prof. Th.M. Starink, MD, PhD - Dermatology Prof. H.P. van Geijn, MD, PhD - Obstetrics and Gynaecology Prof. I. van der Waal, MD, PhD - Oral and Maxillofacial Surgery and Pathology Prof. C.M.J.E. Vandenbroucke-Grauls, PhD - Medical Microbiology and Infection control Prof. W.P. Vandertop, MD, PhD - Neurosurgery 14

16 Scientific Research Committee (CWO) The CWO is divided into a section that advises merely animal related protocols and a section that advises patient related protocols and other project proposals. The CWO advises about the research policy and about the feasibility of new research projects upon request of the MB. The CWO advises the MB specifically about the quality and the feasibility of all research proposals that need permission of the ethical committees for patient related or animal related research before they can be realized. Research proposals made on behalf of (inter)nationally recognized joint ventures (EORTC, HOVON, SIOP, SKION) and multi-center studies in which the VUMC is not the main judging committee, are judged only marginally on local feasibility. The CWO also advises on other research proposals for which judgment by the CWO is desired. The CWO gives asked and unasked advice to the MB about the quality of research within CCA/V-ICI. The CWO section for patient related protocols meets twice a month, the CWO section for animal related protocols meets once a month. The VUMC Management Regulations stipulate that the CCA/V-ICI CWO section for patients related protocols is composed of 5 to 9 members. In view of the institute s size and in order to have sufficient expertise in the different research fields, the CWO has been extended to a maximum of 15 members. Scientific Research Committee (CWO) members: M.A. van Agtmael, MD, PhD (till ) A.A. van Bodegraven, MD, PhD J. van den Born, PhD (till ) B.J.M. Braakhuis, PhD A.J.M. van den Eertwegh, MD, PhD M. van Egmond, PhD (from (from ) P. Keblusek, PhD, secretary (till ) G.K. Kuipers, PhD, secretary (from ) F.A.E. Kruyt, PhD A.A. van der Loosdrecht, MD, PhD (chairman) J.J. Oudejans, MD, PhD Prof. E.F. Smit, MD, PhD B. van Triest, MD, PhD E.A. Voskuijl, MD, PhD (from ) B. Wilhelm, PhD CWO (Animal Experiments Committee) members: B.J. Appelmelk, PhD (from ) V. van Beusechem, PhD T. van der Berg, PhD (till ) P. Keblusek, PhD, secretary (till ) Prof. G. Kraal, PhD G.K. Kuipers, PhD, secretary (from ) Prof. R.J. Scheper, PhD, chairman 15

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18 3. Research programs & running projects The research in the four CCA/V-ICI programs: 1. oncogenesis, 2. immunopathogenesis, 3. disease profiling and 4. therapy is described in the next paragraphs. For every CCA/V-ICI research program a summary is given of the current research lines and perspectives for the future are presented. In addition an overview of the ongoing projects is displayed Program 1: Oncogenesis Program leaders: Prof. R.H. Brakenhoff, PhD Prof. H. Joenje, PhD Prof. P.J.F. Snijders, PhD (Dept. Otolaryngology/Head and Neck surgery) (Dept. Clinical Genetics) (Dept. Pathology) The CCA/V-ICI program 1 Oncogenesis covers both basic and translational research and is subdivided in three research lines: 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 cancer pathways and malignant progression are evaluated. In addition, molecular markers are sought that may be utilized for a) assessment of the risk for progression of pre-cancerous lesions, to facilitate clinical decision-making, b) improving secondary or tertiary prevention of cancer, and c) developing high-throughput screening platforms. - Viral oncogenesis focuses on the role of human papilloma viruses (HPVs) and Epstein Barr virus (EBV) in the development of human cancers, such as anogenital cancers, head and neck cancer, 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 pre-malignant disease with an increased sensitivity and specificity compared to currently existing methods, and newly identified markers will be investigated likewise. - Cancer genomics aims at testing progression models for several human cancers, such as head and neck, lung, gastrointestinal and ovarian cancers, using well-characterized 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. - Genetic predisposition aims at understanding the molecular mechanisms of genome destabilization, as related to the occurrence of cancer, both familial and sporadic. Attention is currently focusing on Fanconi anemia (FA), for which the pathway is being unraveled (13 FA genes known to date) and mouse models are being developed. It is recognized that a subset of sporadic cancers may possess a cellular FA phenotype, which might be exploited through targeted therapeutic intervention. A strong aspect of the research brought together in this program is that patient-oriented research is complemented by unique model systems allowing dissecting the carcinogenic process in the laboratory. These model systems include: HPV-transformed cultured keratinocytes mimicking cervical carcinogenesis, conditionally immortalized mucosal keratinocytes allowing unravelling of the carcinogenic cascade mimicking head and neck carcinogenesis, and transgenic animals to study the role of genomic instability in the origin of cancer. Perspectives 17