Manitoba s Leader in Cancer Research. Annual Report Institute of

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1 Manitoba s Leader in Cancer Research Annual Report 2014 Institute of &

2 The Manitoba Institute of Cell Biology (MICB) gratefully acknowledges the following organizations for their on-going support and commitment without which the achievements documented in this report would not have been possible: CancerCare Manitoba Foundation CancerCare Manitoba The University of Manitoba And most especially to those who unselfishly contributed their dollars and biological samples to cancer research and blood disorders 2

3 TABLE OF CONTENTS Director s Executive Summary...2 Manitoba Institute of Cell Biology (MICB)...3 MICB Principal Investigators...4 Research Highlights...6 Distribution of Impact Factors..19 Cited Publications...20 Operating Grants/Funding Allocations...21 Patents...23 Seminars/Workshops/Conferences...25 Senior Investigators...36 Genomic Centre for Cancer Research & Diagnosis.55 Manitoba Tumour Bank Mammalian Functional Genomics Centre MICB Facilities...63 MICB Staff

4 Message from the Director The past year has been a very productive year for researchers at the Manitoba Institute of Cell Biology. We continued to publish our research in high impact journals with an average impact factor of 5. We published close to 50 papers in peer-reviewed journals that will have an impact on cancer, neurological disorders, and blood disorders. Our researchers continue to receive research grant funding of over 10 million dollars from a wide variety of funding agencies. We have seen an increase in funding from the Canadian Breast Cancer Foundation, and Natural Sciences and Engineering Research Council. Unfortunately, we continue to see a decrease in Canadian Institutes for Health Research as they start to re-organize their funding programs. We also observed an increase in trainees and funding in the form of studentship and fellowships. This bodes well as we continue to pursue discoveries that will improve lives of Manitobans. Listed below are some of the highlights from the past year. Our trainees continue to shine in their research accomplishments. We graduated seven students in the past year. One of them (Dr. Dilshad Khan) won the University of Manitoba Apotex Major Award based upon her research. Ms. Laura Thompson won the Terry Fox Research Institute/Manitoba Health Research Council studentship as the top ranked graduate student in cancer research. Finally but not least, Brent Guppy won the Life Sciences Association of Manitoba Most Promising Life Sciences Student Award and the University of Manitoba s Emerging Leader Award. These outstanding achievements are good predictors that we will continue to be at the forefront of research training for years to come. In recognition for the excellence in training in the Institute, a CancerCare Manitoba Training program was created this year. This will provide a platform for integration of training activities through CancerCare Manitoba including the Institute. It will also provide the opportunity to leverage funding from partners. To this end, we have partnered with the Terry Fox Research Institute to provide entrance scholarships to graduate students that will allow these students to travel to Terry Fox funded laboratories to learn new techniques and establish new collaborations. We hope this will be a model for the future. Our Senior Scientists received many operating grants but I want to highlight just a few. Drs. Mai and Gibson received an innovation grant from the Canadian Cancer Society Research Institute. Since the start of this new funding program, our researchers have been successful in obtaining funding. In addition, Drs. Pistorius, Myal and Raouf received funding from the National Sciences and Engineering Research Council. This represents a trend in increased funding from this federal funding agency. Finally we have received multiple grants from the Canadian Breast Cancer Foundation (5 grants in total this year) establishing the Institute as a leader in Breast Cancer Research. As mentioned above, Senior Scientist published their research in high impact journals. Some highlights include Dr. Geoff Hicks publishing in PLoS Genetics about the role his gene FUS plays in ALS. Dr. Jim Davie published in Nucleic Acid Research about alternative splicing regulation of anti-cell death genes. Our newest Senior Scientist Dr. Sashin Katyal got his paper on DNA repair mechanism published in Nature Neuroscience. This represents important findings that will drive the research programs of our scientists. Overall, this confirms that MICB is one of Manitoba s leading research institutes. With the creation of a new research institute that will focus on cancer and blood disorders, we will continue to strive to have significant impact on our understanding, prevention and treatment of cancer and blood disorders. 2

5 The Manitoba Institute of Cell Biology (MICB) was founded in 1969 by CancerCare Manitoba (formerly the Manitoba Cancer Treatment and Research Foundation) and the University of Manitoba. The Institute is associated with the Faculty of Medicine and the Health Sciences Centre and is located on the 5th, 6th and 7th floors of the CancerCare Manitoba (CCMB) building at 675 McDermot Avenue in Winnipeg, Manitoba, Canada. It is dedicated to basic and translational research in biology and its relation to health, with a primary emphasis on cancer and related diseases. Scientists study such challenging problems as the molecular origins of cancer, the role of signal transduction pathways in regulating cell proliferation, cell death, gene expression and platelet function, development of markers of risk of developing invasive breast cancer, neuronal growth and differentiation during development, programmed cell death and the biochemical action of cancer chemotherapeutics. Although not a degree-granting institution, the Institute plays a major role in training scientists, whether graduate or postgraduate students, medical trainees and investigators who come from around the world to work with our staff. Degrees are granted through the Faculty of Medicine, Departments of Human Anatomy and Cell Science, Biochemistry and Medical Genetics, Immunology, Pharmacology and Therapeutics, Physiology and Medical Microbiology. Information on training programs can be obtained from our office and the Dean of Graduate Studies. The Institute s web page address is 3

6 SENIOR SCIENTISTS Dr. SPENCER GIBSON Mechanisms of Cell Death in Leukemia and Tumours Dr. SHANTANU BANERJI Genomics Dr. VERSHA BANERJI Hematological Malignancies Dr. JIM DAVIE Epigenetics 4

7 Dr. GEOFF HICKS Genetics Dr. SARA ISRAELS Platelet Function Dr. JAMES JOHNSTON Chronic Lymphocytic Leukemia Dr. SACHIN KATYAL DNA Damage and Repair 4

8 Dr. ETIENNE LEYGUE Breast Cancer Dr. SABINE MAI Genomic Instability Dr. KIRK MCMANUS Chromosomal Instability Dr. MIKE MOWAT Genetics of Tumor Cell Progression and Drug Response 4

9 Dr. LEIGH MURPHY Breast Cancer Dr. YVONNE MYAL Breast Cancer Dr. MARK NACHTIGAL Ovarian Cancer Dr. STEPHEN PISTORIUS Medical Physicist 4

10 Dr. AFSHIN RAOUF Breast Cancer Dr. RYAN ZARYCHANSKI Blood Disorders and Transfusion Medicine AFFILIATE SCIENTIST Dr. MAGIMAIRAJANLSSAI VANAN Brain Cancer 4

11 Announcements The University announced new funding from the Manitoba Liquor and Lottery Commission and Canadian Friends of Hebrew University for Dr. Hicks and the university s FASD Research Team. The $1.35 million dollar grant will investigate causes and potential treatments for Fetal Alcohol Syndrome (FASD). Dr. Hicks will research understanding the role of nutrition in mitigating the risk and reducing the effects of FASD when women consume alcohol during pregnancy. Great news and great research! Some familiar faces from the Davie and Hicks labs were on CBC news covering the announcement. 6

12 RESEARCH HIGHLIGHTS Yuequin Zhou, a graduate student in Dr. Geoff Hick s lab has published a paper in PLoS Genetics this month. She has discovered a mechanism by which a mutated gene called TLS/FUS aids in the progression of amyotrophic lateral sclerosis (ALS). 6

13 Sabine Mai received a $90,000 grant from the Manitoba Chapter of Canada s Ride for Dad to support her research on circulating tumour cells in prostate cancer. We welcomed representatives from the Canadian Breast Cancer Foundation Prairies/NWT and Federated Co-op Ltd for a cheque presentation on March 13th. Federated Coop donated $1.5m to CBCF- Prairies/NWT to support breast cancer research. The money raised was from their Drink Pink coffee campaign from Co-op gas stations and grocery stores. CBCF is the third largest source of grant revenue and currently supports 7 different research projects at MICB donating nearly $4m over the last 7 years. 7

14 NOTABLE ACCOMPLISHMENTS Sara Israels and Issai Vanan participated in the Inside Ride and raised nearly $5000 for CCMF. Dr. Shantanu Banerji was selected for the front cover of the Manitoba Medical Service Foundation annual magazine 7

15 Dr. Gibson and members of his lab was featured in the April issue of the Wave magazine 7

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17 Drs. Murphy and Raouf were featured on how researchers are working together in the April edition of the Wave magazine. 2

18 Drs. Davie and Katyal were profiled in the May edition of the Wave magazine. Learn about their newly funded research. 2

19 11 Collaborations between Dr. Sara Israels from MICB and Dr. Elizabeth Sellers from MICH discovered differences in the platelets of children that puts them at a higher risk of developing type II diabetes. video?clipid=387418

20 Dr. Davie s research was featured in the 2013 Canadian Cancer Society Research Institute Research Impact Report. search_impact_report_2013?e= /

21 The Manitoba Medical Service Foundation in conjunction with the St. Boniface Hospital Research Centre selected Dr. Versha Banerji as the 11th Annual MMSF / SBRC Richard Hoeschen Memorial Award recipient. 7

22 Supporting CancerCare Manitoba Foundation CancerCare Manitoba Foundation s Kick Cancer campaign was launched with our own Dr. Zarychanski as a physician taking part in the campaign. Dr. Ryan Zarychanski joined MICB as a Senior Scientist in His work on improving blood product utilization was profiled in the Jan/Feb edition of the WAVE magazine avefull-1401.pdf 9

23 On June 13th, the Genomic Research for Cancer and Diagnosis Centre celebrated its 15th anniversary with an Imaging Symposium with a full day of talks from international speakers who have used the GCCRD for their research. 27

24 On May 21st, Liz Henson, Eilean McKenzie- Matwiy and Dan Gietz (UM BMG) met and spoke with the Duchess of Cornwall during the royals visit to Winnipeg. The Duchess thanked the trio for their work and mentorship of the kids on the yeast in space project. Prince Charles, Prime Minister Stephen Harper and his wife Laureen were also in attendance and spoke with the kids directly at their poster. They also spoke with Walter Natynczyk, President of the Canadian Space Agency and former Chief of Defense Staff of the Canadian Forces. 26

25 Eileen McMillan- Ward received the Karol McNeill technician award from the University. This annual award honours an outstanding technician in health sciences based on prolonged service, scientific excellence, leadership and mentorship. Congratulations Eileen for this well-deserved recognition!! At the same time, Kirk McManus received the Ken Hughes Young Investigator s Award from the University. On June 19 th Dr. Spencer Gibson, Director of MICB, presented his annual State of the Institute talk. 27

26 CancerCare Manitoba Research Day Awards For the second consecutive year, the Arnold Portigal Poster award to Laura Thompson The Rick Hester poster award to Dr Sajesh Babu The best oral presentation award to Rebecca Dielschneider 14

27 The 16 th annual CancerCare Manitoba Research Day for trainees in clinical and basic medical sciences was held May 8, Organized by the Medical Staff Association at CancerCare Manitoba, the event is designed to promote oncology and hematology research among trainees. Dr. Lillian Siu from Princess Margaret Hospital was the Keynote Speaker. Laura Thompson - 1st place poster Basic Science Rebecca Dielschneider - 1st place oral Basic Science Iris Gehrke - 2nd place Basic Oral Presentation 12

28 Sajesh Babu - 2nd place basic poster Eric Bouchard - 3rd place basic poster Nan Wang, Nisha Singh and Anthony Sze - Honourable mention basic science poster 12

29 Michael Xu, a grade 12 student in Dr Mai s lab, placed 3 rd at the 2014 at the Sanofi Aventis Biogeneius Challenge for his work characterizing circulating tumour cells in prostate cancer. Grade 9 students Anthony and Robin received an honourable mention at this year s CancerCare Manitoba Research Day for their work in Dr Vanan s lab. 16

30 Simon and Sara Israels Thesis Award Dilshad Khan Recipient 15

31 Merit Award Congratulations to Eileen McMillan-Ward, recipient of the 2014 MICB Merit Award Eileen has worked for Sara Israels for over 28 years. Eileen works tirelessly each year to make Hallowe en extra special for our pediatric oncology cases and does the Challenge for Life 20k walk to help raise money for CancerCare Manitoba Foundation. 35

32 Dr. Greg Hammond, Executive Director, Manitoba Medical Services Foundation presents the Manitoba Medical Services Foundation Award to Yueqin Zhou. Dr. Margaux Storey, Senior Research Scientist at Apotex Fermentation, presents the Apotex Fermentation Award for Excellence in Molecular Biology to Dilshad Khan. Dr. Grant Hatch presents the Emil and Lynette Hain Award for Excellence in Oncology Research to Rebecca Dielschneider. 17

33 Dr. Grant Hatch presents the Rt. Hon. Don Mazankowski Award for Excellence in Oncology Research to Alexandra Kuzyk. Dr. Greg Hammond, Executive Director, Manitoba Medical Services Foundation presents the MMSF Poster Award to Yueqin Zhou. Dr. Brian Postl, Dean of Medicine presents the Dean of Medicine Poster Award to Rebecca Dielschneider. 17

34 Dr. Serge Desnoyers, Assistant Director, CIHR, Institute of Infection and Immunity, presents Rebecca Dielschneider (University of Manitoba), with a CIHR poster award (Gold category). Dr. Serge Desnoyers, Assistant Director, CIHR, Institute of Infection and Immunity, presents Yueqin Zhou (University of Manitoba), with a CIHR poster award (Silver category). Dr. Jay Doering, Dean of Graduate Studies presents the Dean of Graduate Studies Poster Award to Alexandra Kuzyk. 17

35 Brent Guppy, winner of an Honourable Mention in the 2014 Manitoba Health Research Poster Competition, presents his research to the judges. Laura Thompson, winner of an Honourable Mention in the 2014 Manitoba Health Research Poster Competition, presents her research to the judges. 17

36 Highest Impact Factor in Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. Zarychanski R, Abou-Setta AM, Turgeon AF, Houston BL, McIntyre L, Marshall JC, Fergusson DA. JAMA Feb 20;309(7): doi: /jama Review. Erratum in: JAMA Mar 27;309(12):1229. Impact factor = Meta-analyses of hydroxyethyl starch for volume resuscitation--reply. Zarychanski R, Turgeon AF, Abou-Setta AM. JAMA Jun 5;309(21):2209. doi: /jama Impact factor = Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis. Mercier E1, Boutin A, Lauzier F, Fergusson DA, Simard JF, Zarychanski R, Moore L, McIntyre LA, Archambault P, Lamontagne F, Légaré F, Randell E, Nadeau L, Rousseau F, Turgeon AF. BMJ Apr 4;346:f1757. doi: /bmj.f1757. Impact factor = Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and metaanalysis. Azad MB1, Coneys JG, Kozyrskyj AL, Field CJ, Ramsey CD, Becker AB, Friesen C, Abou-Setta AM, Zarychanski R. BMJ Dec 4;347:f6471. doi: /bmj.f6471. Impact factor = Developmental changes in the in vitro activated regenerative activity of primitive mammary epithelial cells. Makarem M, Kannan N, Nguyen LV, Knapp DJ, Balani S, Prater MD, Stingl J, Raouf A, Nemirovsky O, Eirew P, Eaves CJ. PLoS Biol. 2013;11(8):e doi: /journal.pbio Epub 2013 Aug 13. Impact factor = SYK regulates mtor signaling in AML. Carnevale J, Ross L, Puissant A, Banerji V, Stone RM, DeAngelo DJ, Ross KN, Stegmaier K. Leukemia Nov;27(11): doi: /leu Epub 2013 Mar 28. Impact factor =

37 Most cited in Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. Zarychanski R, Abou-Setta AM, Turgeon AF, Houston BL, McIntyre L, Marshall JC, Fergusson DA. JAMA Feb 20;309(7): doi: /jama Review. Erratum in: JAMA Mar 27;309(12):1229. Cited 54 times 2. Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Li L, Chen Y, Gibson SB. Cell Signal Jan;25(1): doi: /j.cellsig Epub 2012 Sep 19. Cited 13 times 3. Determination of neurologic prognosis and clinical decision making in adult patients with severe traumatic brain injury: a survey of Canadian intensivists, neurosurgeons, and neurologists. Turgeon AF1, Lauzier F, Burns KE, Meade MO, Scales DC, Zarychanski R, Moore L, Zygun DA, McIntyre LA, Kanji S, Hébert PC, Murat V, Pagliarello G, Fergusson DA; Canadian Critical Care Trials Group. Crit Care Med Apr;41(4): doi: /CCM.0b013e318275d046. Cited 6 times 4. Helmet legislation and admissions to hospital for cycling related head injuries in Canadian provinces and territories: interrupted time series analysis. Dennis J, Ramsay T, Turgeon AF, Zarychanski R. BMJ May 14;346:f2674. doi: /bmj.f2674. Cited 5 times 5. Targeting class I histone deacetylases in cancer therapy. Delcuve GP1, Khan DH, Davie JR. Expert Opin Ther Targets Jan;17(1): doi: / Epub 2012 Oct 15. Cited 5 times 6. Expression of both estrogen receptor-beta 1 (ER-β1) and its co-regulator steroid receptor RNA activator protein (SRAP) are predictive for benefit from tamoxifen therapy in patients with estrogen receptor-alpha (ER-α)-negative early breast cancer (EBC).Yan Y, Li X, Blanchard A, Bramwell VH, Pritchard KI, Tu D, Shepherd L, Myal Y, Penner C, Watson PH, Leygue E, Murphy LC. Ann Oncol Aug;24(8): doi: /annonc/mdt132. Epub 2013 Apr 11. Cited 5 times 19

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41 Platforms Through the support of Cancer Care Manitoba, University of Manitoba, National Cancer Institute of Canada, Canadian Institutes of Health Research, Guardian Angels, Jean Carter group, Nygård International Ltd., it is our goal to support cancer research locally, nationally and internationally, through provision of anonymized, processed, and annotated cancer tissues and data as appropriate to address specific research questions. To achieve this while adhering to the highest standards for protection of privacy of patients, and promoting the highest scientific and ethical standards for research to benefit all Canadians. Delivering a comprehensive mouse functional genomics resource for discovery & preclinical research. The Manitoba Institute of Cell Biology is an international leader and major innovator in Functional and Cancer Genomics. With the recent completion of the human genome, the next major hurdle for the Human Genome Project will be to discover what these genes do. Given that we know there are as many as 5,000 human diseases with a genetic determinant, this new field of functional genomics will have a tremendous impact on health care and prevention. Our disease focus is clearly cancer. Through the support of Cancer Care Manitoba, University of Manitoba, National Cancer Institute of Canada, Canadian Institutes of Health Research, Guardian Angels, Jean Carter group, Nygård International Ltd., it is our goal to support cancer research locally, nationally and internationally, through provision of anonymized, processed, and annotated cancer tissues and data as appropriate to address specific research questions. To achieve this while adhering to the highest standards for protection of privacy of patients, and promoting the highest scientific and ethical standards for research to benefit all Canadians. The Manitoba Institute of Cell Biology provides a DNA sequencing service. This service is available for investigators at the University of Manitoba and research facilities associated with the University of Manitoba. Initially established in April 1997, the MICB Sequencing Facility had optimized the sequencing procedure and was able to offer sequencing results at a fraction of the cost at other facilities. This advantage existed for about 10 years; however, as the technology matured our sequencers and throughput could not compete with newer technology. As such, in May 2010 we negotiated an agreement with Eurofins MWG Operon to out source our sequencing requirement to them. NGS was developed to produce genome sequencing at a reasonable cost. A Next Generation Sequencing platform has been established within the Manitoba Institute of Child Health. This platform, created in partnership with the University of Manitoba-Faculty of Medicine, CancerCare Manitoba, the Canada Foundation for Innovation, and the Manitoba Research and Innovation Fund will give Manitoba researchers the tools required to advance discoveries in areas such as epigenetics, cardiovascular research, cancer, diabetes, stem cell biology and other areas of human disease. 55

42 PATENTS CancerCare Manitoba Mai, Sabine Mai, Sabine Telomeric Disk Method of Detecting & Monitoring Cancer using 3D Analysis of Centromeres CentroView Mai, Sabine Method of Monitoring Genomic Instability Using 3D Microscopy Mai, Sabine Mai, Sabine / Havicauva Methods of Diagnosis or Detection Using 3D Analysis TeleView/BRCA Method & System for the 3D Analysis of Chromosomes ChromoView Hicks, Geoff A Novel SMART shrna System for Disease Diagnosis & Therapy Eisenstat, David / Gibson, Spencer Leygue, Etienne Los, Marek Los, Marek Los, Marek Murphy, Leigh University of Manitoba Mutation In The Pro-Apoptotic Protein BNIP3 As A Biomarker For Solid Tumors SBAM Promoter Anticancer, Antimicrobial And Immuno-Suppressive Properties Of Brevinin- Like Peptides From Rana Ridibunda Anticancer Peptides Derived From A Viral Protein Apoptin (VP3) A Novel Role For BAX In The Bystander Effect Phosphorylation of Estrogen Receptor Alpha Other Banerji, Versha Kinase Inhibitors and methods of use thereof 24

43 RESEARCH SEMINARS In the past year, guest lecturers included: Dr. Philippe Georgel Department of Biological Sciences Cell Differentiation and Development Center Byrd Biotechnology Science Center Marshall University Dr. Asish K. Ghosh Assistant Professor of Medicine College of Medicine Mayo Clinic Dr. Keith Bonham Senior Research Scientist, Saskatchewan Cancer Agency Professor, Division of Oncology Associate member, Dept. of Biochemistry, University of Saskatchewan Dr. Deepa Sampath Assistant Professor, Division of Hematology Department of Internal Medicine, Ohio State University Dr. Meghan Azad Postdoctoral Fellow Department of Pediatrics University of Alberta Investigating the Complex Interplay Between Diet, Epigenetics, and Cancer Microvesicle Mediated Crosstalk in B- Cell Chronic Lymphocytic Leukemia: Implications in Disease Progression" Epigenetic reprogramming in cancer: A tale of two Kinases Epigenetic modulation of mirna in CLL "Discoveries from Dirty Diapers: Environmental Exposures and the Infant Gut Microbiome" 25

44 The MICB ANNUAL RETREAT was held at the Victoria Inn and Convention Centre in Brandon, Manitoba on September 20-22, 2013 This year s theme was Platforms. Dr. Susan Newbigging, Director, Pathology Core, Centre for Modeling Human Disease at The Toronto Centre for Phenogenomics gave a talk about the type of experiments they can do with animal models. 28

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47 2013 MICB/BMG BBQ Thank you Don! 31

48 The MICB Christmas party at the CanadInn was a success with fellowship, good food and gifts for all. A special appearance from a guy in a red suit made one elf very happy. It was nice to talk with people outside the work environment and relax for a few hours. Gifts were donated from the PI s and various sponsors. MICB Christmas Party 32

49 Volunteers who handed out treats to our little visitors at MICB A mountain of candy donated for Halloween! The kids from pediatrics did some trick or treating through CancerCare. The first thank you goes to Eileen McMillan-Ward for decorating MICB and coordinating all the activities to include MICB in this special day. Also we have to thank Cheryl McFaddin at Cadbury for the chocolates, Marlene and her family for the pencils, stickers and chips, Flossy, Johnny and Darlene from St Vital Walmart for the wagon wheels and cookies, Ken Leslie at Royal Bank for full sized boxes of Smarties, Craig Poleshuk from Polo Park Boston Pizza for crayons, activity books, cookies, and a coupon for a free kids meal, McDonald s for the apple slices, Old Dutch for the chips, and most importantly, everyone in MICB for their donations of candy and cash to help make Halloween a special day for kids with cancer! 33