Cancer Biology Research Group 2003 Annual Report Department of Oncology, Faculty of Medicine, University of Calgary Introduction Of the 26 full members of the Cancer Biology Research Group, 16 hold appointments with the Department of Oncology, 6 being primary appointments. This report will cover the activities of the 16 members holding appointments as well as the general activities during the past year of the group as a whole. 2003 has been another busy year for the Cancer Biology Research Group (CBRG) and we continue to thrive, expanding our membership and research endeavors. CBRG is the basic science arm of cancer research in Southern Alberta and it is currently undergoing a metamorphosis which will see it effectively disappear as the Southern Alberta Cancer Research Institute (SACRI) begins to take shape during 2004 and into 2005. Driven by the University of Calgary, SACRI will be one of the 6 new Institutes within the Faculty of Medicine. It will also endeavor to become the umbrella organization bringing together basic scientists, clinicians, epidemiologists and others involved in cancer research activities focusing on six programmatic research themes: 1. Integrative Brain Tumor Research Program, 2. Radiation Oncology & Mechanisms for DNA Damage and Repair, 3. Molecular Epidemiology, 4. Experimental and Molecular Therapeutics in Pediatric Oncology, 5. Palliative Care in Oncology, 6. Cancer and Aging. Membership Of the 16 Full Members reported, all of them hold academic appointments within the Faculty of Medicine, University of Calgary and 7 also hold clinical appointments at either Tom Baker Cancer Center or the Alberta Children’s Hospital. Our ability to recruit and accommodate more members is primarily limited at present by the availability of laboratory space although we did see the addition of one new recruit to the Group during 2003. It is anticipated that this lack of space will be addressed by the opening of the University of Calgary’s Research Innovation Center during 2005. Fund raising is currently underway for the equipping of this space once construction is completed. In anticipation of this new space becoming available we, in the fall of 2003, lifted the hiring freeze we had implemented early on in the year. Recruitment was reinitiated, following discussion with the Faculty of Medicine, and we have initiated the recruitment of two new faculty in conjunction with the Integrative Brain Tumor Research Program team. Academic Advancement Education The group offers 3 graduate courses, each of which are a semester long. 2003 saw initiation of the plan for a change in the delivery of these courses to a more modular program offering students a more diverse spectrum of opportunity. This change is aimed at reflecting the diversity of research activities within the group; the desire to encourage more translational research and to allow students to take advantage of the interdisciplinary approach to research fostered by the group. Research In line with our programmatic themes, the creation of the endowed chairs has enabled us to recruit and retain excellence among our senior researchers. These chairs are: Endowed Chair in Brain Tumor Research – Dr Greg Cairncross The Engineered Air Chair in Cancer Research – Dr Susan Lees-Miller Endowed Chair in Pediatric Oncology – Dr Max Coppes Endowed Chair in Molecular Epidemiology – currently in creation The Integrative Brain Tumor Research Program under Drs Greg Cairncross and Peter Forsyth continues to demonstrate successes in the field of brain tumor research and treatment including their leading edge work with reovirus treatments in Phase I clinical trials and DNA mapping in brain tumor tissue. Dr Susan Lees-Miller was awarded the Engineered Air Chair in 2003 and has already begun to establish links with the radiation oncologists at TBCC in trying to understand the mechanisms of DNA damage and repair and its relationship to radiation therapy treatment of cancer. Dr Max Coppes was announced as the newly identified holder of the chair in Pediatric Oncology early in 2004. This is an exciting new position and is the foundation of the thematic program of investigation in Experimental Therapeutics in Childhood Cancer. The creation of an Endowed Chair in Molecular Epidemiology will support the leading edge work of the Epidemiology group who are national leaders in the application of the new discipline of molecular epidemiology. Molecular epidemiology marries the classic population based data gathering techniques of epidemiology with large-scale tissue banking and high throughput molecular analysis and bioinformatics. Service Our members hold a variety of administrative positions within the Faculty, the University and a variety of affiliate organizations such as Calgary Health Region and the Alberta Cancer Board. We continue to strive to both inform and shape the work done in areas of academic development, research endeavors and patient care. Demonstrating this in 2003 was Dr Frans van der Hoorn’s appointment to the position of Associate Dean of Graduate Education with the Faculty. We are also working towards the formation of the Southern Alberta Cancer Research Institute addressing issues such as membership, governance, space allocation and integration with the Alberta Cancer Board (ACB). New Investigator Salary Support The provision of three salaries by the ACB to the CBRG in support of the recruitment of new scientific faculty just beginning on their independent careers has been a great success. During 2003 we have again utilized one of these salaries to provide a start up package to a new recruit to the group and this recruit has since been able to secure external salary funding from the AHFMR. This will be the third successive year where we have been able to utilize these funds in this bridging fashion to recruit to the group (Dr Shirin Bonni) and have the salary later freed up through the success of the recruits in securing external funding. We attribute this success to the high standard of excellence we look for when recruiting to the group. 2003 has seen us begin the recruitment of one new member in conjunction with the Brain Tumor program as previously discussed and the plans are to continue to utilize these salaries to support our programmatic themes. 2004’s will be used to support the Mechanisms of DNA Damage and Repair Program and the 2005 will likely be used in support of the Pediatric Oncology Research Program. Core Facilities CBRG receives funding toward a number of core facilities thorough the ACB RIP and NIP funding streams. These facilities continue to be not only essential, invaluable tools for the Cancer Research Community but are integral to the functioning of several endeavors of the entire Faculty of Medicine at the University of Calgary. These facilities are: RIP funded Core Facilities: - Embryonic Stem Cell Facility (ACB / U of C joint venture) - Flow Cytometry (ACB / U of C joint venture) - Hybridoma Facility (ACB / U of C joint venture) - Histology Facility (SACRC venture) NIP funded Core Facilities - Microarray (ACB / U of C joint venture) We have decided to undertake a process of external review of the RIP funded core facilities to ensure they continue to operate efficiently and effectively and this review is scheduled to commence early 2004. We feel this review is critical in assisting us to decide on long-term plans for each of the Facilities and prioritization of resources. The decision to close the Tumor Modeling Facility during the past year demonstrates our commitment to ensuring demand and output of each facility is adequate and the most effective use of our available resources. Summary 2003 has been not only a year of continued research successes but one which has seen us begin a process of change and review that will alter the face of research organization in Southern Alberta. We are welcoming this opportunity to work with colleagues across the spectrum of cancer research activity as well as those involved in other arms of medical research. We believe that interdisciplinary discussion will lead to collaborations and synergies that will only enhance the research activities and successes that will be seen in the coming years. Following is the information for each of our full Members. Summary of Members with Department of Oncology Appointments Primary Appointments Dr Max Coppes Dr Peter Forsyth Dr Rhiannon Hughes Dr Don Morris Dr Derrick Rancourt Dr Stephen Robbins Secondary Appointments Dr Oliver Bathe Dr Chris Brown Dr Greg Cairncross Dr Randal Johnston Dr Rene LaFreniere Dr Karl Riabowol Dr David Schreimer Dr Frans van der Hoorn Dr David Waisman Dr Dallan Young Christopher Brown - M.D., FRCP (C )– Professor, Departments of Medicine, Oncology and Biochemistry & Molecular Biology Faculty of Medicine, University of Calgary; Chair, Cancer Biology Research Group; Associate Director (Research) Tom Baker Cancer Center; Director, Southern Alberta Cancer Research Center ;Director, Southern Alberta Cancer Research Institute; Medical Director, Graft Engineering Group, Alberta Bone Marrow and Stem Cell Transplant Program; Attending Physician, Alberta Bone Marrow and Stem Cell Transplant Program; Attending Physician Division of Hematology cbrown@ucalgary.ab.ca Tel: (403) 220 8247 Fax: (403) 283 8727 Publications Trus, M.R., Bordeleau, L., Pihl, C., McGeer, A., Minden, M.D. and Brown, C.B. Clinical Manifestations Associated with the Aberrant Expression of the Soluble Granulocyte–Macrophage Colony Stimulating Factor Receptor in Patients Presenting with Hematological Malignancies. Brit. J. Haematol., 121(1): 86-93, 2003. Pelley, J and Brown, C.B. Soluble receptor variants in the GM-CSF, IL-3, IL-5 receptor family. Mod Asp Immunobiol. 3(2): 60-63, 2003 (invited review). Grant Support Canadian Institutes of Health Research (CIHR) Alberta Cancer Board Anaemia Institute for Research & Education Multiple Sclerosis Society of Canada Canadian Institutes of Health Research (CIHR) Cangene Corporation Personnel Carin Pihl Jennifer Pelley Jeff Dai Jaclyn Harris Bruno Tillier Janel Nadeau Tammy Unruh Role and Regulation of the soluble GMCSF Receptor Structural variants of the soluble GMCSF Receptor; the role of proteolysis and documentation of mixed receptor populations in leukemic serum. 10/2002 – 09/2005 $89,989 05/2002-04/2003 $10,704 Glycophorin A-mediated Hemolysis: The Implications of a Novel Mechanism Therapeutic Potential of a Soluble GMCSF Receptor in EAE. Co-PI, Provincial Graduate Training Program in Translational Cancer Research (ACB/UC/UA/CIHR/NCIC) GM-CSF Cytoxicity Project. 07/2001 – 06/2003 $30,000 11/2002 – 03/2004 $35,000 06/2003-05/2009 $1.8 million $29,435 Laboratory Technician/Manager Graduate Student, Ph.D.Biochemistry & Molecular Biology Graduate Student, MScMedical Sciences Graduate Student, MScMedical Sciences and Provincial Graduate Training Program in Translational Cancer Research Graduate Student, MSc Medical Sciences. Undergraduate Student, Bchm 528/530 Graduate Student, MSc Immunology Training Program Dr. Mike Brain Janis Querido Honorary Research Professor Administrator J. Gregory Cairncross – Professor, Dept. Head of Clinical Neurosciences; Regional Clinical Department Head, Calgary Health Region, ACF Chair in Brain Tumor Research. jgcairnx@ucalgary.ca Tel: (403) 944 1260 Fax: (403) 270 7878 Publications Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartman C, Laughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR, Louis DN. Gene expression-based classification of malignant gliomas correlate better with survival than histological classification. Cancer Res 63: 1602-1607, 2003 Betensky RA, Louis DN, Cairncross JG, Analysis of a molecular genetic neuro-oncology study with partially biased selection. Biostatistics 4: 167-178, 2003 Forsyth PA, Weaver S, Fulton D, Brasher PMA, Sutherland G, Stewart D, Hagen NA, Barnes P, Cairncross JG, De Angelis LM. Prophylactic anticonvulsants in patients with brain tumour. Can J Neurol Sci 30: 106-112, 2003 Van den Bent M, Chinot O, Cairncross JG. Temozolomide: recent developments in the molecular characterization and treatment of oligodendroglial tumors. Neuro-Oncology 5: 128-138, 2003 Bélanger K, Macdonald D, Cairncross JG, Gertler S, Forsyth P, Burdette-Radoux S, Bergeron D, Ludwin S, Wainman N, Eisenhauer E. A phase II study of topotecan in patients with anaplastic oligodendroglioma and anaplastic mixed oligoastrocytoma. Investigational New Drugs 21: 473-480, 2003 Lauren, EA, Barrett, H. Childs, N., Paleologos, N., Kaminer, L., Rosenfeld, S., Salzman, E., Finlay, J.L., Gardner, S., Peterson, K., Hu, W., Swinnen, L., Bayer, R., Forsyth, P., Stewart, D., Smith, AM, Macdonald, DR, Weaver, S., Ramsey, DA., Nimer, SD, DeAngelis, LM, Cairncross, JG High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma. J Neuro Oncol 65(2): 127-134, 2003 Grant Support Alberta Cancer Board Alberta Cancer Board 2003-2005 $34,995 2003 $17,497.50 Personnel Guo Wei Xu Dr. Sajeel Chowdhary Magdalena Zlatescu Danielle Sikander Graduate student Post Doctoral Fellow in Neuro-Oncology PhD, Research Associate Administrative Manager, Department of Clinical Neurosciences Doug Demetrick – Assistant Professor, Departments of Pathology and Oncology; Director, ACB Histology Facility demetric@ucalgary.ca Tel: (403) 220 2890 Fax: (403) 283 8727 Publications Demetrick DJ. Targeting Cancer Treatment: The Challenge of Anatomical Pathology to the Analytical Chemist. The Analyst. 128:995-97. 2003. Murthy SK and Demetrick DJ. New Approaches to Fluorescence In Situ Hybridization. Cell Imaging Techniques: Methods and Protocols, Douglas J. Taatjes and Brooke T. Mossman Editors. Humana Press, New York. In Press. Grant Support Alberta Cancer Board Kids Cancer Care Foundation Calgary Laboratory Services/MDS Alberta Cancer Board Ruth Barker Foundation Personnel Peter Lewkonia Adrian Box Structure-Function Correlates of p16-related CDK Inhibitor proteins A Novel Strategy to Evaluate the Regulation of the Hypoxic Response of Pediatric Solid Tumour Cells Translational Proteomics $35,000 2003-2005 $50,000 per annum Histology Infrastructure Grant 2002-2005 $80,000 per annum 2002-2003 $40,000 Cytosine Methyltransferase Regulation in Breast Cancer 2002-2003 $50,000 Medical Undergraduate Student Medical Sciences Graduate Student Laura Fursey Natalie Rezansoff Carol Yuen Linda Ganley Eli Akbari Jason Morrin Dr. Steve Loken Dr. Majid Akbari Medical Sciences Graduate Student BMB Graduate Student Undergraduate (MDSC 530 student) Undergraduate (MDSC 530 student) Undergraduate Summer Research Student Undergraduate Summer Research Student Medical Resident Medical Resident Rhiannon M. Hughes - MD (University of Toronto), MSC (University of Calgary), FRCPC (Paediatrics, Genetics), FCCMG; Assistant Professor, Departments of Oncology and Medical Genetics; Medical Director; Cancer Genetics Research Clinic, Tom Baker Cancer Centre; Chair, Alberta Cancer Genetics Program; rhughes@ucalgary.ca Tel: (403) 220-2715 Fax: (403) 283 8727 Publications Gillan T, Hughes R, Godbout R, Grundy.PE, The Simpson-Golabi-Behmel Gene, GPC3, is not involved in sporadic Wilms Tumorigenesis. Am J Med Genet 122A(1):30-6, 2003 Adler D, Kanji N, Trpkov K, Fick G, Hughes RM HPC2/ELAC2 Gene Variants Associated with Incident Prostate Cancer J Human Genetics, published electronically, Nov 19, 2003 http://www.springerlink.com Grant Support Alberta Cancer Board – Research Initiative Program Canadian Breast Cancer Foundation, Alberta/NWT Chapter Calgary Health Region Alberta Health and Wellness, Health Strategies Genotype Analysis of Xenobiotic Metabolizing Enzymes as Predictors of Familial Breast Cancer Susceptibility CHK2 gene variants and inherited breast cancer susceptibility A Pilot Study Evaluating the Impact of Counselling/Decision Aids on Informed Decision Making of Women with Hereditary Breast & Ovarian Cancer Susceptibility and their Physicians Alberta Cancer Genetics Program, Epidemiology 2001 - 2002 (renewed for 2003) $79,755 per annum 2003 - 2005 $72,000 2003 - 2004 $25,000 2002 – present $250,000 Division Personnel Nimira Kanji Sasha Lipichuk Administrative Assistant Database 4th year undergraduate summer student, Queen's University, Kingston ON MD Janis Querido Randall N Johnston - B.Sc. (University of Victoria), Ph.D. Biological Sciences (Stanford University), Professor, Biochemistry & Molecular Biology, Faculty of Medicine, Professor, Oncology, Faculty of Medicine, Adjunct Professor, Biological Sciences, Faculty of Science, Associate Scientific Staff Member, Tom Baker Cancer Centre; rnjohnst@ucalgary.ca Tel: (403) 220-8692 Fax: (403) 503 5225 Publications Liu GR, Edwards K, Eisenstark A, Fu YM, Liu WQ, Sanderson KE, Johnston RN, Liu SL. (2003) Genomic diversification among archival strains of Salmonella typhimurium LT7. J. Bacteriol. 185: 2131-42. Vieyra D, Senger DL, Toyama T, Muzik H, Brasher PMA, Johnston RN, Riabowol K, Forsyth PF. (2003) Altered subcellular localization and low frequency of mutations of ING1 in human brain tumors. Clin Canc Res 9: 5952-5961. Grant Support Canadian Institutes of Health Research Resistance to Reovirus Oncolysis Personnel Dr, Shu-Lin Liu Dr. Catherine Egan Research Associate Post-Doctoral Fellow 2002 to 2005 $120,998 per annum Derrick Rancount - B.Sc. (University of Guelph); Ph.D., (Queen’s University); Associate Professor, Departments of Biochemistry & Molecular Biology and Oncology, Program Director, Embryonic Stem Cell Targeted Mutagenesis Facility; Program Director, Masters of Biomedical Technology rancourt@ucalgary.ca Tel: (403) 220-2888 Fax: (403) 220 3029 Publications Wride MA, Mansergh FC, Adams S, Everitt R, Minnema S, Rancourt DE and Evans MJ (2003) Expression Profiling and Gene Discovery in the Mouse Lens. Mol Vis 9, 360. Lees-Miller JP, Guo J, Somers JR, Roach DE, Sheldon RS, Rancourt DE, Duff HJ (2003) Selective Knockout of Mouse ERG1 B Potassium Channel Eliminates I(Kr) in Adult Ventricular Myocytes and Elicits Episodes of Abrupt Sinus Bradycardia. Mol Cell Biol. 23,1856-62. Thomas B, Woltjen K and Rancourt DE (2003) Deep Screening of Recombination Proficient Bacteriophage Libraries. Biotechniques 34, 36-8. Sarna JR, Larouche M, Marzban H, Sillitoe RV, Rancourt DE and Hawkes R (2003) Patterned Purkinje Cell Degeneration in Mouse Models of Niemann-Pick type C Disease. J. Comp. Neurol. 456, 279-91. Grant Support Canadian Foundation for Innovation Canadian Institutes of Health Research Canadian Institutes of Health Research Stem Cell NCE 2003 to 2004 $4,361,847 2003/04 to 2006/03 $48,390 per annum 2003/04 to 2006/03 $71,678 per annum 2003/04 to2005/03 $41,250 per annum 2003/04 to 2005/03 Stem Cell NCE $87,000 Alberta Cancer Board Canadian Institutes of Health Research Canadian Institutes of Health Research Canadian Institutes of Health Research U.S. National Institutes of Health Margaret Gunn Endowment Personnel Jacqueline Hance Eileen Rattner Shiying Liu Hui Xu Multi-User Maintenance Grant Lab Manager Technician Technician Technician 04/2002 to 03/2005 $40,000 2002/04 to 2005/03 $130,000 per annum 2001/04 to 2004/03 $45,000 per annum 2000/09 to 2003/08 $55,000 per annum 2000/04 to 2003/03 $68,754 per annum 2002 to2004 $54,060 Sandy Nishikawa Rebecca Everitt Kenichi Ito Navneet Sharma Nicole Zur Nieden Guolian Meng Colleen O’Sullivan Knut Woltjen Stephanie Minnema Jillian Ungarian Magdalena Swanson Brad Thomas Lin Tang Feodor Price Kim Melton Administrative Assistant Technician Informaticist Research Associate Research Associate Postdoctoral Fellow Postdoctoral Fellow Ph.D., Medical Student Ph.D. Ph.D. M.Sc. Ph.D. M.Sc. M.Sc. BSc Student BSc Student/Technician Tiz Reiter Karl T. Riabowol - B.Sc. Hon (Simon Fraser University, B.C.); PhD. (U of Arkansas for Medical Sciences, Little Rock, AR); PDF (Cold Spring Harbor Lab); Professor, Departments of Biochemistry & Molecular Biology and Oncology; Associate Scientific Staff Member, Tom Baker Cancer Centre; Director (SACRC) Hybridoma Facility, SACRC Cell Bank. karl@ucalgary.ca Tel: (403) 220-8695 Fax: (403) 270 0834 Publications Berardi, P., Meyyappan, M., and Riabowol, K. A Novel Transcriptional Inhibitory Element in the 5'-untranslated Region of the Cyclin D1 Gene Contributes to Senescenceinduced Gene Expression. J. Biol. Chem. 278: 7510 - 7519 (2003). Hara, Y., Zheng, Z., Evans, S., Malatjalian, D., Riddell, D., Guernsey, D., Wang, L., Riabowol, K. and Casson, A. ING1 and p53 Tumor Suppresser Gene Alterations in Adenocarcinomas of the Esophagogastric Junction. Cancer Letters 192:109-116 (2003). Tallen, G., Riabowol, K. And Wolff, J.E.A. Expression of p33ING1 mRNA and Chemosensitivity in Brain Tumour Cells. Anticancer Res. 23: 1631-1635 (2003). Kataoka, H., Bonnefin, P., Vieyra, D., Feng, X., Hara, Y., Miura, Y., Nakabayashi, H., Joh, T., Vaziri, H., Harris, C. and Riabowol, K. ING1 Represses transcription by Direct DNA Binding and Through Effects on p53. Cancer Research 63: 5785-5792 (2003). Vieyra, D., Senger, D.L., Toyam, T., Muzik, H., Brasher, P.M., Johnston, R.N., Riabowol, K. and Forsyth, P.A. Altered Subcellular Localization and Low Frequency of Mutations of ING1 in Human Brain Tumors. Clinical Cancer Res. 9: 5952-5961 (2003). Toyama, T., Iwase, H., Yamashita, H., Hara, Y., Sugiura, H., Zhang, Z., Fukai, I., Miura, Y., Riabowol, K. and Fujii, Y. p33 (ING1b) Stimulates the Transcriptional Activity of the Estrogen Receptor Alpha via its Activation Fur Domain. J Steroid Biochem. Mol. Biol. 87: 57-63 (2003). Tallen, G., Kaiser, I., Krabbe, S., Lass, U., Hartmann, C., Henze, G., Riabowol, K. and von Deimling, A. No ING1 Mutations in Human Brain Tumours but reduced Expression in High Malignancy Grades of Astrocytoma. Published Online – International Journal of Cancer (January, 2004). Grant Support CIHR IIPP CIHR Alberta Cancer Board Infrastructure CIHR Pilot Project CIHR Editorship Cancer Research Society Personnel Dr. Paul Bonnefin Dr. Yasuo Hara Dr. Hiromi Kataoka Dr. Keith Wheaton Dr. Keiko Suzuki Diego Vieyra Philip Berardi Jason Quarrie Pinaki Bose Mike Russell Brad Unryn Xiolan Feng Gong Wei Administrative Assistant 1999 to2004 $ 765,000 2000 to 2003 $788,123 2002 to 2005 $426,000 2002 to2004 $140,000 2003 to 2004 $45,000 2003 to 2006 $15,000 2003 to 2005 $118,000 Post-Doctoral Fellow Trainees Post-Doctoral Fellow Trainees Post-Doctoral Fellow Trainees Post-Doctoral Fellow Trainees Post-Doctoral Fellow Trainees Ph.D. Ph.D. Ph.D. Ph.D. Ph.D. M.Sc. M.Sc. M.Sc. Tiz Reiter Stephen M. Robbins - B.Sc. Honours (York University), Ph.D. (University of British Columbia), AHFMR Senior Scholar, Canada Research Chair in Cancer Biology; Associate Professor, Departments of Biochemistry & Molecular Biology and Oncology; Staff Scientist, Tom Baker Cancer Center; Director, Southern Alberta Microarray Facility; Graduate Education Coordinator Medical Sciences; srobbins@ucalgary.ca Tel: (403) 220-4304 Fax: (403) 283 8727 Publications Yipp, B.G., Robbins,S.M., Resek, M.E., Baruch, D.I., Looareesuwan, S. and Ho, M. 2003 Src-family Kinase Signaling Modulates the Adhesion of Plasmodium falciparum on Human Microvascular Endothelium. Blood 101: 2850-2857. Ridyard, M.S. and Robbins, S.M. 2003 Fibroblast growth factor-2 induced signaling through lipid raft associated Fibroblast Growth Factor Receptor Substrate-2 (FRS2). J.Biol. Chem. 278:13803-13809. Kerfoot, S.M., Lord, S.E., Bell, R.B., Gill, V., Robbins, S.M. and Kubes, P. (2003) Human fractalkine mediates leukocyte adhesion but not capture under physiological shear conditions; a mechanism for selective monocyte recruitment. Eur. J. Immunol. 33: 729739. Gauthier, L.R. and Robbins, S.M. (2003) Ephrin Signaling: One raft to rule them all? One raft to sort them? One raft to spread their call and in signaling bind them? Life Sciences 74:207-216. Grant Support CIHR CIHR CIHR Alberta Cancer Board CIHR CIHR Cancer Research Society Co-Investigator A Transdisciplinary Training Program in Diseases of Immunopathogenesis and Inflammation Co-Investigator - Strategic Training Program in Translational Cancer Research Co-ApplicantLive Cell Imaging Maintenance Co-applicant Proteomics and Functional Genomics Leading to Therapeutics Compartmentalized signaling in hematopoietic cells Ephrin-mediated cellular communication Co-applicant - Molecular and cellular characterization of 2003-2008 $256,000 2003-2008 $300,000 2003-2006 $42,000 2003-2004 $450,000 2002-2006 $139,114 per annum 2002-2006 $165,685 per annum 2002-2004 $60,000 per annum AHFMR CIHR Cancer Research Society CIHR CIHR AHFMR Personnel S.A. Bisson Box D. Browman Laura Gauthier A. Klimowicz L.D. Zajchowski A. McDermid E. Long M.E. Resek E. Ujack T. MacRae P. Thirukkumaran E. Tam Administrative Assistant glioma invasion Compartmentalized Signaling Co-applicant - Leukocyte Recruitment and Effector Mechanisms in the Inflammatory Response Cbl-mediated targeting of oncogenes Co-applicant - Matrix metalloproteinases in MS: Environmental influence, biology, pathology and therapeutic strategies. CRC Chair Tier II - Molecular Genetics of Cancer Salary Support 2001-2005 $72,111 per annum 2001-2004 $351,143 per annum 2003-2005 $59,000 per annum 2001-2005 $989,650 per annum 2001-2005 $100,000 per annum 2001-2005 Ph.D. M.Sc. Ph.D. Ph.D. Ph.D. Ph.D. Ph.D. M.Sc. Research Associate Research Assistant Research Associate Research Associate Research Assistant Ruth Malus David C. Schriemer - Ph.D., Analytical Chemistry, (University of Alberta); Assistant Professor, Departments of Biochemistry & Molecular Biology, Oncology and Pharmacology & Therapeutics; Adjunct Assistant Professor, Chemistry, Faculty of Science; Director, Southern Alberta Mass Spectrometry Centre. dschriem@ucalgary.ca Publications Tel: (403) 210-3811 Fax: (403) 220 0834 John K. Chik, David C. Schriemer, 2003, “Hydrogen/Deuterium Exchange Mass Spectrometry of Actin in Various Biochemical Contexts”, Journal of Molecular Biology, 334, 373-385. Yaping Yu, Wei Wang, Qi Ding, Ruiquiong Ye, Dawn Chen, Dennis Merkle, David C. Schriemer, Katheryn Meek, Susan Lees-Miller, 2003 “DNA-PK Phosphorylation Sites in XRCC4 are Not Required for Survival After Radiation or for V(D)J Recombination”, DNA Repair, 2, 1239-1252. Nora W.C. Chan, Darren F. Lewis, Philip J. Rosner, Michele A. Kelly, David C. Schriemer, 2003, “FAC-MS Assay Technology for Multiple Stages of Drug Discovery: Applications of a Chromatographic Biosensor”, Analytical Biochemistry, 319, 1-12. Gordon W. Slysz, David C. Schriemer, 2003, “On-column digestion of proteins in aqueous-organic solvents”, Rapid Communications in Mass Spectrometry, 17, 10441050. Yi Zhang, Marjorie Fournier, Janine D. Wildschut, Alain Dolla, Johanna K. Voordouw, David C. Schriemer, Gerrit Voordouw, 2003, “Function of oxygen resistance proteins in the anaerobic, sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough”, Journal of Bacteriology, 185, 71-79. Grant Support ACB Pilot Project Grant Alberta Ingenuity Fund Alberta Ingenuity Fund Personnel Dominic Orsler Ella Ng Sheena Lambert Carey Sheu CJ Baker Andrea Sullivan Dr. John Chik New Approaches for the Discovery and MolecularLevel Characterization of Anti-Mitotic The Development of Advanced Biomolecular Interaction Analysis Tools for the Post-Genomic Era Co-principal investigator, Alberta Centre for Carbohydrate Science 2003-2004 $34,500 2002-2004 $44,000 awarded July 2003 2002-2007 $200,000 awarded Sept. 2003 PhD, Manager, Southern Alberta Mass Spectrometry Centre MSc, Mass Spectrometrist BSc, Junior Technician MSc, Senior Technician MSc, Computer Scientist/Bioinformatics BSc, Junior Technician Post-Doctoral Fellow Administrative Assistant Tiz Reiter Frans A. van der Hoorn - PhD (Biochemistry, University of Nijmegen, Nijmegen, The Netherlands); Professor, Department of Biochemistry & Molecular Biology; Adjunct Professor, Department of Oncology; Associate Dean (Graduate Science Education); Associate Dean (Medicine), Faculty of Graduate Studies; Graduate Coordinator, Biomedical Technology, Faculty of Medicine; fvdhoorn@ucalgary.ca Tel: (403) 220-3323 Fax: (403) 283 8727 Publications Zarsky, H.A., Tarnasky, H.A., Cheng. M. and Van der Hoorn, F.A. (2003) Novel RING finger protein OIP1 binds to conserved amino acid repeats in sperm tail protein ODF1. Biol. Reprod., 68, 543 - 552. Peer reviewed (impact factor 3.7) Sadek, C.M., Jiménez, A., Kieselbach, T., Nord, M., Davis, E.C., Spyrou, G., Gustafsson, J.A., Oko, R., van der Hoorn, F.A. and Miranda-Vizuete, A. (2003) Characterization of human thioredoxin-like 2 (Txl-2), a novel microtubule-binding thioredoxin. J. Biol. Chem., 278, 13133 - 13142. Peer reviewed (impact factor 6.7) Bhullar, B., Zhang, Y., Junco, A., Oko, R. and Van der Hoorn, F.A. (2003) Association of Kinesin light chain with Outer dense fibers in a microtubule-independent fashion. J. Biol. Chem., 278, 16159 - 16168. Peer reviewed (impact factor 6.7) Grant Support Canadian Institutes for Health Research Canadian Institutes for Health Research Canadian Institutes for Health Research Canadian Institutes for Health Research STEP program support Personnel Y. Ruan Y. Zhang C. Fitzgerald Y. ZhanG Dr. R. Oko H. Tarnasky M. Cheng S. Zaman K. Dong K. Dong M.H. Modarressi Janis Querido Motor molecules in spermatogenesis Motor molecules in spermatogenesis Protein interactions in sperm tails Co-investigator, Strategic Training Program Grant, Translational Cancer Research Summerstudentship Award (K. Dong), Analysis of sperm tail proteins 1999-2003 $59,224 per annum 2003-2008 $32,365 per annum 2000-2005 $163,128 per annum 2003-2008 $150,000 per annum 3400 Ph.D. Ph.D. M.Sc. Ph.D. Visiting Professor Research Technician (part-time) Lab Manager, Research Technician Technician summerstudent High School Science Enrichment Program high school student MD, PhD Administrative Assistant David M. Waisman - Ph.D. (University of Manitoba); Professor, Department of Biochemistry & Molecular Biology and Oncology, Faculty of Medicine waiseman@ucalgary.ca Tel: (403) 220 3022 Fax: (403) 270 0737 Publications Choi, K-S., Fogg, D.K., Yoon, C.-S. and Waisman, D.M. (2003) P11 Regulates Extracellular Plasmin Production and Invasiveness of HT1080 Fibrosarcoma Cells. FASEB J. 17, 235-246. Hirasawa, K., Nishikawa, S. G., Norman, K. L., Coffey, M. C., Thompson, B. G., Yoon, C. S., Waisman, D. M., and Lee, P. W. (2003) Systemic reovirus therapy of metastatic cancer in immune-competent mice. Cancer Res. 63, 348-353. MacLeod, T.J., Kwon, M., Filipenko, N.R., and Waisman, D.M. (2003) Phospholipidassociated annexin A2-S100A10 heterotetramer and its subunits:Characterization of the interaction with tissue plasminogen activator, plasminogen and plasmin. J. Biol. Chem. 278, 25577-25584. Le, D.M., Besson A., Fogg, D.K., Choi, K.S., Waisman, D.M., Goodyer, C.G., Rewcastle, B., and Yong, V.W. (2003) Exploitation of astrocytes by glioma cells to facilitate invasiveness: a mechanism involving matrix metalloproteinase-2 and the urokinase-type plasminogen activator-plasmin cascade. J Neurosci. 23, 4034-43. Zhang, L., Fogg, D.K. and Waisman, D.M. (2003) RNA Interference-mediated silencing of the S100A10 gene attenuates plasmin generation and invasiveness of Colo 222 colorectal cancer cells. J. Biol. Chem. epublished October 20. Filipenko, N., MacLeod, T., Yoon, C.-S., and Waisman, D. M. (2003) Annexin A2 is a novel RNA-binding protein. J. Biol. Chem. epublished December 11, 2003. Caplan, J.F., Filipenko, N.R., Fitzpatrick, S.L. and Waisman, D.M. The Regulation of Annexin A2 by Reversible Glutathionylation. Journal of Biological Chemistry. published Dec. 11, 2003. Grant Support National Institutes of Health Plasminogen Regulation by Annexin II Tetramer CIHR Regulation of Angiostatin Formation by Annexin II Tetramer Alberta Heart and Stroke Regulation of Fibrinolysis Foundation by Annexin II Tetramer Personnel Mr. Darin Fog Mr. Nolan Filipenko Ms. Mijung Kwon Mr. Libo Zhang Mr. Yi Zhang Dr. Chang-Soon Yoon Vi Sommerfeld 1998-2003 $ 240,640 per annum 04/2002 – 04/2007 $ 145,080 per annum 07-2003 – 07-2006 $ 55,000 per annum PhD, Student PhD, Student PhD, Student MSc Student PhD student Post-Doctoral Fellow Administrative Assistant Dallan Young - PhD (University of Utah); Professor, Departments of Biochemistry and Molecular Biology and Oncology, Faculty of Medicine dallan@ucalgayr.ab.ca Tel: (403) 220 3030 Fax: (403) 283 8782 Publications Huang, T. Y., N. A. Markley, and D. Young. “Nak1, an essential germinal center (GC) kinase regulates cell morphology and growth in Schizosaccharomyces pombe.” J. Biol. Chem. 278:991-997. Grant Support Medical Research Council Investigation of the Mkh1 signaling pathway in fission yeast. National Cancer Institute of The functions of yeast Canada proteins related to the human p33ING1 tumor suppressor National Cancer Institute of The role of yeast Ing1Canada related proteins in chromatin modification and gene expression Medical Research Council Investigation of the role of Pnk1 in DNA repair in fission yeast Personnel Timothy Huang Chad Johnston Tao Qi Ruth Malus 1999/04- 2003/03 $352,255 2000/07 - 2003/06 $309,462 2003/07- 2007/06 $114,249 this year 2002/10- 2004/09 Principle Investigator $73,435 this year Ph.D. candidate M.Sc. candidate M.Sc. candidate Administrative Assistant Faculty who have Presented Internationally Cairncross JG, Invited lecture: “Managing glioma in the molecular era” Frontiers in Clinical Neuroscience Plenary Lecture. American Academy of Neurology, Honolulu, Hawaii, April 2003. Cairncross JG, Invited lecture: “Managing glioma in the molecular era” American Society of Therapeutic Radiation Oncology, Salt Lake City, Utah, October 2003. Riabwol KT, ARCR Sam Walton Research Forum, Little Rock, AR “Function of the ING1 proteins in Programmed Cell Death & Aging” March 3, 2003. Riabwol KT, SLU Cancer Center Research Seminar, St. Louis, MO “Function of the ING1 Tumor Suppressor in Cancer & Aging” March 5, 2003. Robbins SM, Invited speaker at the 4th International Symposium on Receptor Mechanisms, Signal Transduction and Drug Effects, Fukui, Japan. Talk entitled “Distinct compartmentalization of transmembrane and GP1-anchored ephrins within lipid rafts”. May 22, 2003 David C. Schriemer, Guest Lecturer at Pfizer Global Research – Groton CT, June 4, 2003. Waisman DM, Role of Annexin II Heterotetramer in Tumor Growth and Invasiveness Department of Biochemistry and Molecular Biology, Rice University, November 17, 2003. Waisman DM, Regulation of Cancer Cell Proteinases by S100A10 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, November 24, 2003. van der Hoorn FA, Kinesin light chain3 can cluster mitochondria. XVII North American Testis Workshop, Phoenix, AZ, March 2003. van der Hoorn FA, Kinesin light chain3 can cluster mitochondria. 36th Annual Meeting of the Society for the Study of Reproduction, July 2003, Cincinnati, Ohio. Significant Publications Vieyra DS, Toyama T, Muzik H, Brasher PMA, Johnston RN, Riabowol K, Forsyth PA. The candidate tumor suppressor gene ING1 in human brain tumours.. Clinical Cancer Research December 2003 (Impact Factor 5.991) Vieyra D, Senger DL, Toyama T, Muzik H, Brasher PMA, Johnston RN, Riabowol K, Forsyth PF. (2003) Altered subcellular localization and low frequency of mutations of ING1 in human brain tumors. Clin Canc Res 9: 5952-5961. (Impact Factor 5.991) Berardi, P., Meyyappan, M., Riabwol, K. – A Novel Transcriptional Inhibitory Element in the 5’-untranslated Region of the Cyclin D1 Gene Contributes to Senescence-induced Gene Expression. J. Biol. Chem. 278: 7510-7519, 2003 (Impact Factor 6.696) Kataoka, H., Bonnefind, P., Vieyra, D., Feng, X., Hara, Y., Miura, Y., Nakabayashi, H., Joh, T., Vaziri, H., Harris, C., Riabowol, K. – ING1 Represses Transcription in Direct DNA Binding and Through Effects on p53. Cancer Research 63: 5785-5792, 2003. (Impact Factor 8.318) Ridyard, M.S., Robbins, S.M. – Fibroblast growth factor-2 induced signaling through lipid raft associated Fibroblast Growth Factor Receptor Substrate-2 (FRS2). J. Biol. Chem. 278: 13803-13809, 2003. (Impact Factor 6.696) John K. Chik, David C. Schriemer, 2003, “Hydrogen/Deuterium Exchange Mass Spectrometry of Actin in Various Biochemical Contexts”, Journal of Molecular Biology, 334, 373-385. (Impact Factor 5.359) Sadek, C.M., Jiménez, A., Kieselbach, T., Nord, M., Davis, E.C., Spyrou, G., Gustafsson, J.A., Oko, R., van der Hoorn, F.A. and Miranda-Vizuete, A. (2003) Characterization of human thioredoxin-like 2 (Txl-2), a novel microtubule-binding thioredoxin. J. Biol. Chem., 278, 13133 - 13142. Peer reviewed (Impact factor 6.696) Bhullar, B., Zhang, Y., Junco, A., Oko, R., van der Hoorn, F.A. – Association of Kinesin light chain with Outer dense fibers in a microtubule-independent fashion. J. Biol. Chem. 278:16159-16168, 2003 (Impact Factor 6.696) Choi, K.S., Fogg, D.K., Yoon, C.S., Waisman, D.M. – P11 Regulates Extracellular Plasmin Production and Invasiveness of HT1080 Fibrosarcoma Cells. FASEB J. 17: 235-246, 2003 (Impact Factor 7.252) MacLeod, T.J., Kwon, M., Filipenko, N.R., Waisman, D.M. – Phospholipid-associated annexin A2-S100A10 heterotetramer and its subunits: Characterization of the interaction with tissue plasminogen activator, plasminogen and and plasmin. J. Biol. Chem. 278: 25577-25584, 2003 (Impact Factor 6.696) Zhang, L., Fogg, D.K. and Waisman, D.M. - RNA Interference-mediated silencing of the S100A10 gene attenuates plasmin generation and invasiveness of Colo 222 colorectal cancer cells. J. Biol. Chem. epublished October 20, 2003. (Impact Factor 6.696) Filipenko, N., MacLeod, T., Yoon, C.-S., and Waisman, D. M. - Annexin A2 is a novel RNA-binding protein. J. Biol. Chem. epublished December 11, 2003. (Impact Factor 6.696) Caplan, J.F., Filipenko, N.R., Fitzpatrick, S.L. and Waisman, D.M. - The Regulation of Annexin A2 by Reversible Glutathionylation. J. Biol. Chem. epublished Dec. 11, 2003. (Impact Factor 6.696) Huang, T. Y., N. A. Markley, and D. Young. “Nak1, an essential germinal center (GC) kinase regulates cell morphology and growth in Schizosaccharomyces pombe.” J. Biol. Chem. 278:991-997. (Impact Factor 6.696)