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
Central nervous system (CNS) tumors are among the most prevalent forms of childhood cancers accounting for nearly 20% of all new cases (Canadian Cancer Society Statistics, 2015). Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor and is currently divided into 4 distinct molecular subtypes.: WNT, SHH, Group 3 and Group 4. Extensive genetic, molecular and clinical heterogeneity between these subgroups has made it difficult to assess the functional relevance of genes to tumor progression. The Werbowetski-Ogilvie lab employs high throughput flow cytometry-based screening platforms to identify and subsequently characterize novel roles for cell surface markers in regulating diverse medulloblastoma phenotypes both in vitro and in vivo. Utilizing a wide variety of functional assays including measures of self-renewal, differentiation, invasion and proliferation in vitro as well as tumor growth in vivo using xenograft models, the lab is currently investigating the role of CD271, also known as p75 neurotrophin receptor (p75NTR) or nerve growth factor receptor (NGFR), in regulating stem cell properties of SHH variant medulloblastoma cells.
In addition, the lab utilizes neural derivatives from human embryonic stem cells (hESCs) as a model system to study the mechanisms contributing to pediatric brain tumorigenesis. Using this powerful cell resource as both a complement to and surrogate for existing cell lines and heterogeneous patient samples, the goal is to better understand how genes such as the transcription factor orthodenticle homeobox 2 (OTX2) regulate the balance between self-renewed and differentiation to either prevent or sustain oncogenic properties.
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
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)
Dr. Brent Guppy, Post-Doctoral Fellow
Dr. Jamie Zagozewski, Post-Doctoral Fellow
Ludivine Morrison, Lab Mgr / Research Tech
Ghazaleh Shahriary, Research Tech