STEPHEN TOULMIN

Principle Investigator:

Olli Kallioniemi, M.D., Ph.D., Director, Institute for Molecular Medicine Finland (FIMM), Biomedicum Helsinki and Director of the Academy of Finland Centre of Excellence on Translational Genome-scale Biology, Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku. Laboratory address: Medical Biotechnology, PharmaCity, Itäinen Pitkäkatu 4C, P.O. Box 106, FI-20521 Turku, Finland.

Tel. +358-20-722 2800. Fax +358-20-722 2840. Email: olli.kallioniemi(at)vtt.fi.

Biography:

Dr. Olli Kallioniemi (born 1960) received his M.D. in 1984 and Ph.D. in 1988 at the University of Tampere in Finland. Olli Kallioniemi held several positions in the US over a 10-year period, most recently (1995-2002) as the Head of Translational Genomics Section at the Cancer Genetics Branch, National Human Genome Research Institute, at NIH, Bethesda, Maryland. Since 2003, he has been Professor of Medical Biotechnology at the VTT Technical Research Centre of Finland with a joint appointment at the University of Turku. Academy of Finland Professorship in 2004-2007. He is an author of 226 publications and editor or member of the editorial board of six journals. He has participated as an invited lecturer in over 90 meetings in the past 4 years. Inventor of 12 issued patents, with a focus on technology development, such as Comparative Genomic Hybridization (CGH) in 1992, tissue microarrays in 1998 and cell- based RNAi microarrays in 2003. EACR young investigator award in 1994, Anders Jahre Prize in 1998, NIH Director’s lecture in 2000, Medal of the Swedish Medical Society in 2003, National Academy of Sciences (Finland) in 2005, EMBO Membership in 2006, and Harold G. Pritzker Memorial Lecture at the University of Toronto in 2006.

Personnel:

Senior/staff scientists: Matthias Nees, Ph.D., Maija Wolf, Ph.D. Postdoctoral researchers: Kristine Kleivi, Ph.D. Kirsi Hellström, Ph.D., Kristiina Iljin, Ph.D.,

Ph.D-students: Elmar Bucher, M.Sc., Sami Kilpinen, M.Sc., Rami Mäkelä, M.Sc., Juha Rantala, M.Sc., Sirkku Pollari, M.Sc., Mari Peltola, M.Sc., Henrik Edgren M.Sc. Henri Sara, M.Sc., Ville Härmä, M.Sc., Santosh Gupta, M.Sc., Tommi Pisto, M.Sc., Pekka Tiikkainen, M.Sc., Kalle Ojala, M.Sc.

Technicians: Pirjo Käpylä, Pauliina Toivonen. Trainee/undergraduate student: Niina Tiensuu. Coordinator: Heidi Sid, M.Sc.

Description of the Project:

The overall purpose of this research program is to develop and apply high-throughput technologies to understand mechanisms of progression of breast and prostate cancers as well as to identify novel therapeutic targets and leads.

The aims of the various research programs are to:

1) identify target genes for genetic alterations in breast and prostate cancer

screening (chemical genomics) to infer gene functions in living cells, with particular attention towards cancer-specific vulnerabilities and steroid-dependent signalling and

3) translate the molecular discoveries towards drug development and clinical diagnostics.

We have developed unique high-throughput technologies, such as cell microarrays, protein lysate microarrays, in silico profiling of gene expression in clinical samples and many others. We are using advanced bioinformatics, chemoinformatics, and systems biological data integration methods to characterize the deregulation of cancer cell functions. The research is carried out in collaboration between the Medical Biotechnology Centre of the VTT Technical Research Centre of Finland and the Turku Centre for Biotechnology. Our group is a recipient of the EU Marie Curie Centre of Excellence Grant (2004-2008) and coordinates Academy of Finland Centre of Excellence in Translational Genome-Scale Cell Biology in collaboration with the Biomedicum Helsinki. Our research includes a multi-disciplinary research training program (for Ph.D. students and postdocs) focusing on biochip technologies, bioinformatics, systems biology, translational cancer research and drug development.

Collaborators:

Tomi Mäkelä, Lauri Aaltonen, Jussi Taipale, Päivi Ojala (Biomedicum Helsinki, partners of Academy of Finland Centre of Excellence in Translational Genome-Scale Biology), Spyro Mousses (Translational Genomics Research Institute, USA), Outi Monni (Biomedicum Helsinki), Jaakko Astola, Olli Yli-Harja (Tampere University of Technology), Antti Poso (University of Kuopio), John Eriksson, Riitta Lahesmaa, Päivi Koskinen, Klaus Elenius and many others from the University of Turku. We have over 100 collaborators in current EU projects such as PRIMA, Moltools, Cancerdegradome, RIGHT, Epitron, ENLIGHT, Proteome Binders (FP6) as well as Genica, APO-SYS, Prosper and Meta-Cancer (FP7).

Funding:

The Academy of Finland, Tekes, Finnish Cancer Organizations and Sigrid Juselius Foundation. Our biggest source of funding

comes from the EU 6th _{and 7}th _{framework projects, including the}

collaborative programs mentioned above and the Marie Curie Centre of Excellence Grant.

Selected Publications:

Edgren H, Kallioniemi O (2006), Integrated breast cancer genomics. Cancer Cell 6: 453-455

Iljin K, Wolf M, Edgren H, Gupta S, Kilpinen S, Skotheim RI, Peltola M, Smit F, Verhaegh G, Schalken J, Nees M, Kallioniemi O. (2006), TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming. Cancer Res 66: 10242-10246.

Kallioniemi O. (2004) Profile of a tumor. Nature, 428:379-382. Huusko P, Ponciano-Jackson D, Wolf M, Kiefer JA, Azorsa DO, Tuzmen S, Weaver D, Robbins C, Moses T, Allinen M, Hautaniemi S, Chen Y, Elkahloun A, Basik M, Bova GS, Bubendorf L, Lugli A, Sauter G, Schleutker J, Ozcelik H, Elowe S, Pawson T, Trent JM, Carpten JD, Kallioniemi OP, Mousses S. (2004), Nonsense-

mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. Nat. Genet., 36:979-983.

Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, Moses TY, Hostetter G, Wagner U, Kakareka J, Salem G, Pohida T, Heenan P, Duray P, Kallioniemi O, Hayward NK, Trent JM, Meltzer PS. (2003) High frequency of BRAF mutations in nevi. Nat. Genet., 33:19-20.

Mousses S, Caplen NJ, Cornelison R, Weaver D, Basik M, Hautaniemi S, Elkahloun AG, Lotufo RA, Choudary A, Dougherty ER, Suh E, Kallioniemi O. (2003) RNAi Microarray Analysis in Cultured Mammalian Cells. Genome Res., 13:2341-2347.

Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R, Meltzer P, Gusterson B, Esteller M, Kallioniemi O-P, Borg Å, Trent J. (2001) Gene Expression Profiles of Hereditary Breast Cancer. N. Engl. J. Med., 344:539-48.

Srivastava M, Bubendorf L, Srikantan V, Fossom L, Nolan L, Glasman M, Leighton X, Fehrle W, Pittaluga S, Raffeld M, Koivisto P, Willi N, Gasser TC, Kononen J, Sauter G, Kallioniemi OP, Srivastava S, Pollard HB.(2001) ANX7, a candidate tumor suppressor gene for prostate cancer. Proc. Natl. Acad. Sci. USA, 98:4575-80.

Group 1: Kainu T, Juo SHH, Desper R, Schäfferm AA, Gillanders E, Rozenblum E, Freas-Lutz D, Weaver D, Stephan D, Bailey-Wilson J, Kallioniemi O-P, and 4 other groups: (2000) Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus. Proc. Natl. Acad. Sci. USA, 97: 9603-9608.

Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi O-P: (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nature Medicine, 4:844-847.

From left to right: Pekka Tiikkainen, Henri Sara, Kristiina Iljin, Rami Mäkelä, Niina Tiensuu, Sirkku Pollari, Kirsi Hellström, Pauliina Toivonen, Juha Rantala, Tommi Pisto, Mattias Nees. Front: Mari Björkman, Kristine Kleivi, Ville Härmä, Olli Kallioniemi, Heidi Sid, Santosh Gupta, Pirjo Käpylä and Elmar Bucher.