Dr. Tamra Werbowetski-Ogilvie received her HSBc of Science in Biology at the University Western Ontario in 2000. She completed her PhD in the Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University in 2005. Dr. Werbowetski-Ogilvie completed her postdoctoral training at McMaster University in the area of human embryonic stem cells in 2010 under the supervision of Dr. Mick Bhatia following which she joined the University of Manitoba as a Principal Investigator in the Department of Biochemistry & Medical Genetics and the Regenerative Medicine Program in November, 2010. Dr. Werbowetski-Ogilvie currently holds a Tier II Canada Research Chair in Neuro-Oncology and Human Stem Cells.
The Cellular and Molecular Mechanisms Contributing to Stem Cell Function and Heterogeneity in Medulloblastoma
My research program is entirely dedicated to the study of the pediatric brain tumor, medulloblastoma, the most common malignant primary brain tumor in children. Medulloblastoma is a disease of dysregulated neurodevelopment and is made up of at least 4 different subgroups. One of these subgroups, called Group 3, is highly aggressive and has a very poor outcome. My lab has recently shown that Group 3 medulloblastomas appear to be driven by “control switches” - the factors that help choose which genes are turned on or off inside the cells. We want to know how one of these factors, called OTX2, controls other genes, interacts with other proteins, and regulates tumor growth. In addition, we also want to determine whether OTX2 plays different roles in medulloblastoma growth vs. normal neurodevelopment. Understanding how these control switches help make medulloblastomas grow offers fresh opportunities to target Group 3 tumors, prevent tumor spread, and decrease the toxicity of therapy for children with this devastating disease.
In addition to Group 3 medulloblastoma, we are also working on another subgroup called Sonic Hedgehog (SHH) medulloblastoma. SHH tumors are very high risk, as some patients survive while many others unfortunately die as a consequence of recurring disease and drug resistance. Thus, one of our goals is to identify new drugs to treat SHH medulloblastomas. We recently discovered that SHH medulloblastoma cells are killed with a drug named selumetinib. This is exciting as selumetinib can actually get inside the tumor and is currently in clinical trials for the treatment of other children’s brain cancers. Now, we are testing the combination of selumetinib with other known cancer fighting drugs with the ultimate goal of increasing survival and enhancing the quality of life for those children who survive long term.
Zagozewski J, Shahriary GM, Coudière Morrison L, Saulnier O, Stromecki M, Fresnoza A, Palidwor G, Porter CJ, Forget A, Ayrault O, Hawkins C, Chan JA, Vladoiu MC, Sundaresan L, Arsenio J, Taylor MD, Ramaswamy V, and Werbowetski-Ogilvie TE. 2020. An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate.
Nature Communications. July 20; 11(1):3627. https://doi.org/10.1038/s41467-020-17357-4
Liang L, Coudière Morrison L, Tatari N, Stromecki M, Fresnoza A, Porter CJ, Del Bigio MR, Hawkins C, Chan JA, Taylor MD, Ramaswamy V*, Werbowetski-Ogilvie TE*. 2018. CD271+ cells are diagnostic and prognostic and exhibit elevated MAPK activity in SHH medulloblastoma. *denotes co-corresponding authorship. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-18-0027.
Stromecki M, Tatari N, Morrison LC, Kaur R, Zagozewski J, Palidwor G, Ramaswamy V, Skowron P, Wölfl M, Milde T, Del Bigio MR, Taylor MD, Werbowetski-Ogilvie T. 2018 Jan 27. Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma. Mol Oncol, doi: 10.1002/1878-0261.12177. [Epub ahead of print]
Liang L*, Aiken C*, McClelland R, Coudière Morrison L, Tatari N, Remke M, Ramaswamy V, Issaivanan M, Ryken T, Del Bigio MR, Taylor M, Werbowetski-Ogilvie T. 2015. Characterization of novel biomarkers for subtype-specific medulloblastoma cell phenotypes. Oncotarget, 6(36): 38881-38900.
*These authors contributed equally to this work.
Kaur R, Coudière Morrison L, Aiken C, Rao R, Del Biogio MR, Rampalli S, Werbowetski-Ogilvie TE. 2015. OTX2 exhibits cell context-dependent effects on cellular and molecular properties of human embryonic neural precursors and medulloblastoma cells. Disease Models & Mechanisms, 8(10): 1295-1309.
Coudière Morrison M*, McClelland R*, Aiken C, Bridges M, Wang X, Del Bigio MR, Taylor MD, Werbowetski-Ogilvie TE. 2013. Deconstruction of medulloblastoma cellular heterogeneity reveals differences between the most highly invasive and self-renewing phenotypes. Neoplasia, 15(4):384-398.
Werbowetski-Ogilvie TE*, Coudière Morrison L, Fiebig-Comyn A, Bhatia M*. 2012. In vivo generation of neural tumors from neoplastic pluripotent stein cells models early human pediatric brain tumor formation. Stem Cells. 30(3): 392-404.
*Denotes co-corresponding authorship
Canadian Institutes of Health Research Project Grant
Novel therapeutic targets for Group 3 medulloblastoma stem cells ($1,208,700)
CancerCare Manitoba Foundation Multidisciplinary Team Grant
Exploring the Regulatory Landscape of Medulloblastoma Stem Cells ($449,136)
Canada Research Chair (CRC) Tier II in Neuro-Oncology and Human Stem Cells
Identification of New Molecular Targets that Regulate Brain Tumour Progression ($500,000)
Rally Foundation for Pediatric Cancer Research
Combinatory therapies for SHH medulloblastoma ($100,000 US dollars).
CancerCare Manitoba Foundation
Combinatory therapies for SHH medulloblastoma ($65,562)
*Reduced award due to overlap with Rally grant
Alex’s Lemonade Stand Foundation Innovation Grant
Characterization of novel OTX2-semaphorin gene signaling pathways regulating the "grow and go" arms of highly aggressive medulloblastomas ($249,078 US dollars).
Canadian Institutes of Health Research Operating Grant
Functional Characterization of Novel Biomakers for Subtype-Specific Medulloblastoma Cell Phenotypes ($614,470)
Canadian Institutes of Health Research Project Grant (CIHR)
Characterization of novel OTX2-semaphorin gene signaling pathways regulating the "grow and go" arms of highly aggressive medulloblastomas ($100,000)
Natural Sciences and Engineering Research Council of Canada (NSERC)
Investigating the Role of Lin28A in Human Embryonic Neural Lineage Function ($192,000)
Children's Hospital Research Institute of Manitoba (CHRIM)/Kenzie's Kauze
Delineating the OTX2 regulatory network: Targeting the "grow and go" arms of the most
aggressive medulloblastomas ($50,000)
The University Collaborative Research Program (UCRP)/Department of Biochemistry & Medical Genetics with M Nachtigal (PI), K McManus
Investigating Chromosomal Instability in Ovarian Cancer Stem Cells ($50,000)
Brain Canada Platform Support Grant with C Anderson (PI)
Manitoba Neuroimaging Platform (300,000)
The Paul H.T. Thorlakson Foundation Fund
Exploring the Role of OTX2 in Medulloblastoma Tumor Initiation and Progression ($29,928)
Canada Foundation for Innovation (CFI): Leaders Opportunity Fund
Establishment of a Human Embryonic Stem Cell Laboratory and Brain Tumour Invasion Imaging Unit to Study Malignant Brain Tumour Progression ($312,500)
University of Manitoba
611-745 Bannatyne Avenue, BMSB
Winnipeg, MB R3E 0J9
Dr. Victor Gordon, Post-Doctoral Fellow
Stephanie Borlase, MSc Student