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

l: (403) 220 8247Fax: (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) / Role and Regulation of the soluble GM-CSF Receptor / 10/2002 – 09/2005
$89,989
Alberta Cancer Board / Structural variants of the soluble GM-CSF Receptor; the role of proteolysis and documentation of mixed receptor populations in leukemic serum. / 05/2002-04/2003
$10,704
Anaemia Institute for Research & Education / Glycophorin A-mediated Hemolysis: The Implications of a Novel Mechanism / 07/2001 – 06/2003
$30,000
Multiple Sclerosis Society of Canada / Therapeutic Potential of a Soluble GM-CSF Receptor in EAE. / 11/2002 – 03/2004
$35,000
Canadian Institutes of Health Research (CIHR) / Co-PI, Provincial Graduate Training Program in Translational Cancer Research (ACB/UC/UA/CIHR/NCIC) / 06/2003-05/2009
$1.8 million
Cangene Corporation / GM-CSF Cytoxicity Project. / $29,435

Personnel

Carin PihlLaboratory Technician/Manager

Jennifer PelleyGraduate Student, Ph.D.Biochemistry & Molecular Biology

Jeff DaiGraduate Student, MScMedical Sciences

Jaclyn HarrisGraduate Student, MScMedical Sciences and Provincial Graduate Training Program in Translational Cancer Research

Bruno Tillier Graduate Student, MSc Medical Sciences.

Janel Nadeau Undergraduate Student, Bchm 528/530

Tammy Unruh Graduate Student, MSc Immunology Training Program

Dr. Mike BrainHonorary Research Professor

Janis QueridoAdministrator

J. Gregory Cairncross– Professor, Dept. Head of Clinical Neurosciences; Regional Clinical Department Head, Calgary Health Region, ACF Chair in Brain Tumor Research.

l: (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 / 2003-2005
$34,995
Alberta Cancer Board / 2003
$17,497.50

Personnel

Guo Wei Xu Graduate student

Dr. Sajeel Chowdhary Post Doctoral Fellow in Neuro-Oncology

Magdalena ZlatescuPhD, Research Associate

Danielle SikanderAdministrative Manager, Department of Clinical

Neurosciences

Doug Demetrick – Assistant Professor, Departments of Pathology and Oncology; Director, ACB Histology Facility

l: (403) 220 2890Fax: (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 / Structure-Function Correlates of p16-related CDK Inhibitor proteins / $35,000
Kids Cancer Care Foundation / A Novel Strategy to Evaluate the Regulation of the Hypoxic Response of Pediatric Solid Tumour Cells / 2003-2005
$50,000 per annum
Calgary Laboratory Services/MDS / Translational Proteomics / 2002-2005
$80,000 per annum
Alberta Cancer Board / Histology Infrastructure Grant / 2002-2003
$40,000
Ruth Barker Foundation / Cytosine Methyltransferase Regulation in Breast Cancer / 2002-2003
$50,000

Personnel

Peter Lewkonia Medical Undergraduate Student

Adrian BoxMedical Sciences Graduate Student

Laura FurseyMedical Sciences Graduate Student

Natalie RezansoffBMB Graduate Student

Carol YuenUndergraduate (MDSC 530 student)

Linda GanleyUndergraduate (MDSC 530 student)

Eli AkbariUndergraduate Summer Research Student

Jason MorrinUndergraduate Summer Research Student

Dr. Steve LokenMedical Resident

Dr. Majid AkbariMedical 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;

l: (403) 220-2715Fax: (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

Grant Support

Alberta Cancer Board – Research Initiative Program / Genotype Analysis of Xenobiotic Metabolizing Enzymes as Predictors of Familial Breast Cancer Susceptibility / 2001 - 2002 (renewed for 2003)
$79,755 per annum
Canadian Breast Cancer Foundation, Alberta/NWT Chapter / CHK2 gene variants and inherited breast cancer susceptibility / 2003 - 2005
$72,000
Calgary Health Region / 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 / 2003 - 2004
$25,000
Alberta Health and Wellness, Health Strategies Division / Alberta Cancer Genetics Program, Epidemiology Database / 2002 – present
$250,000

Personnel

Nimira Kanji4th year undergraduate summer student, Queen's University, Kingston ON

Sasha LipichukMD

Administrative AssistantJanis 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;

l: (403) 220-8692Fax: (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 / 2002 to 2005
$120,998 per annum

Personnel

Dr, Shu-Lin LiuResearch Associate

Dr. Catherine EganPost-Doctoral Fellow

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

l: (403) 220-2888Fax: (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 / 2003 to 2004
$4,361,847
Canadian Institutes of Health Research / 2003/04 to 2006/03
$48,390 per annum
Canadian Institutes of Health Research / 2003/04 to 2006/03
$71,678 per annum
Stem Cell NCE / 2003/04 to2005/03
$41,250 per annum
Stem Cell NCE / 2003/04 to 2005/03
$87,000
Alberta Cancer Board / 04/2002 to 03/2005
$40,000
Canadian Institutes of Health Research / 2002/04 to 2005/03
$130,000 per annum

Canadian Institutes of

Health Research

/ Multi-User Maintenance Grant / 2001/04 to 2004/03
$45,000 per annum
Canadian Institutes of Health Research / 2000/09 to 2003/08
$55,000 per annum
U.S. National Institutes of Health / 2000/04 to 2003/03
$68,754 per annum
Margaret Gunn Endowment / 2002 to2004
$54,060

Personnel

Jacqueline HanceLab Manager

Eileen RattnerTechnician

Shiying LiuTechnician

Hui XuTechnician

Sandy NishikawaTechnician

Rebecca EverittInformaticist

Kenichi ItoResearch Associate

Navneet SharmaResearch Associate

Nicole Zur NiedenPostdoctoral Fellow

Guolian MengPostdoctoral Fellow

Colleen O’SullivanPh.D., Medical Student

Knut WoltjenPh.D.

Stephanie MinnemaPh.D.

Jillian UngarianM.Sc.

Magdalena SwansonPh.D.

Brad ThomasM.Sc.

Lin TangM.Sc.

Feodor PriceBSc Student

Kim MeltonBSc Student/Technician

Administrative AssistantTiz 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.

l: (403) 220-8695Fax: (403) 270 0834

Publications