Senior Scientist, Cancer Research
Ottawa Hospital Research Institute

Acting Program Director, Cancer Therapeutics Program
Ottawa Hospital Research Institute

Associate Professor
University of Ottawa

Glioblastoma is an aggressive and incurable form of brain cancer. My lab has two main projects aimed at improving patient outcomes for this disease:
1. As a consequence of a characteristic set of mutations in tumour suppressor genes and oncogenes, almost all glioblastomas have aberrant activation of a cell signalling pathway known as the PI 3-kinase pathway. We are characterizing this pathway in detail in glioblastoma with the goal of identifying novel therapeutic targets. This research makes use of a set of glioblastoma cell cultures that we have isolated from patients at the Ottawa Hospital. These are then modified using genetic engineering techniques (CRISPR knockout and lentiviral transduction) to identify genes with key roles in glioblastoma pathogenesis.
2. We are developing novel biotherapeutic strategies for glioblastoma treatment. We have engineered a version of the tumour suppressor PTEN that efficiently transfers from cell-to-cell. This is currently undergoing pre-clinical evaluation as a therapeutic, using neural stem cells as delivery vehicles. Additional therapeutic proteins that have the same property of efficient cell-to-cell transfer are also being developed.

Keywords:  cancer; glioblastoma; PI 3-kinase; PTEN; experimental therapeutics

Dr. Lorimer completed a Ph.D. in Biochemistry at the University of Western Ontario and did postdoctoral training at the University of British Columbia and the National Cancer Institute, National Institutes of Health, USA. Currently he is a senior scientist at the Ottawa Health Research Institute and an associate professor in the Departments of Medicine and Biochemistry, Microbiology and Immunology at the University of Ottawa.

Jacques FH, Nicholas G, Lorimer IAJ, Sikati Foko V, Prevost J, Dumais N, Milne K, Nelson BH, Woulfe J, Jansen G, Apedaile BE (2021) The SEJ study: Avelumab in newly diagnosed glioblastoma, Neuro-oncology Advances, accepted for publication

Lavictoire SJ, Jomaa D, Gont A, Jardine K, Cook DP, Lorimer IAJ (2021) Rac guanine nucleotide exchange factors promoting Lgl1 phosphorylation in glioblastoma, Journal of Biological Chemistry, accepted for publication

Ramanathan A and Lorimer IAJ (2021) Engineered cells as glioblastoma therapeutics, Cancer Gene Therapy, March 22, doi: 10.1038/s41417-021-00320-w. 

Lorimer IAJ (2019) Aberrant Rac pathway signalling in glioblastoma, Small GTPases, published online May 6, 1-15

Lavictoire SJ, Gont A, Julian L, Stanford WL, Vlasschaert C, Gray D, Jomaa D, Lorimer IAJ (2018) Engineering PTEN-L for cell-mediated delivery, Molecular Therapy – Methods and Clinical Development, 9: 12-22

Kumar R, Gont A, Perkins T, Hanson JEL, Lorimer IAJ (2017) Induction of senescence in primary glioblastoma cells by serum and TGFb, Scientific Reports, 7: 2156

Gont A, Daneshmand M, Woulfe J, Lavictoire SJ, Lorimer IAJ (2017) PREX1 integrates G protein-coupled receptor and phosphoinositide 3-kinase signaling to promote glioblastoma invasion, Oncotarget, 8: 8559-8573

Jahani-Asl A, Yin H, Soleimani VD, Chang NC, Sincennes M-C, Luchman HA, Puram SV,
Scott AM, Lorimer IAJ, Ligon KL, Weiss S, Rudnicki MA, Bonni A (2016) EGFRvIII Requires OSMR as a Co-Receptor to Drive Glioblastoma Tumorigenesis, Nature Neuroscience, 19:798-806

Restall IJ, Parolin DAE, Daneshmand M, Hanson JEL, Simard MA, Fitzpatrick ME, Kumar R, Lavictoire SJ, Lorimer IAJ (2015) PKCι depletion initiates mitotic slippage-induced senescence in glioblastoma, Cell Cycle, 14: 2938-48

Lorimer IAJ (2015) Atypical PKCι as a target for glioblastoma therapy. Current Cancer Drug Targets 15:136-44

Gont A, Hanson JEL, Lavictoire SJ, Daneshmand M, Nicholas G, Woulfe J, Kassam A, Da Silva VF, Lorimer IAJ (2014) Inhibition of glioblastoma malignancy by Lgl1, Oncotarget, 5, 11541-51

Karapetis C , Jonker D, Daneshmand M, Hanson J, Marginean C, O'Callaghan C, Tebbutt N, Price T, Tu D, Simes J, Zalcberg J, Lorimer IAJ (2014) BRAF, PIK3CA and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer: results from NCIC CTG / AGITG CO.17, Clinical Cancer Research, 20, 744-53  

Liwak U, Jordan LE, Von-Holt SD, Singh P, Hanson JE, Lorimer IA, Roncaroli F, Holcik M (2013) Loss of PDCD4 contributes to enhanced chemoresistance in glioblastoma multiforme through de-repression of Bcl-xL translation. Oncotarget, 4, 1365-72

Goss GD, O'Callaghan C, Lorimer I, Tsao MS, Masters GA, Jett J, Edelman MJ, Lilenbaum R, Choy H, Khuri F, Pisters K, Gandara D, Kernstine K, Butts C, Noble J, Hensing TA, Rowland K, Schiller J, Ding K, Shepherd FA (2013) Gefitinib versus Placebo in Completely Resected Non-Small Cell Lung Cancer, Results of the NCIC CTG BR19 Study. J. Clin. Oncology, 31, 3320-6

Gont A, Hanson JEL, Lavictoire SJ, Parolin DAE, Daneshmand M, Restall IJ, Soucie M, Nicholas G, Woulfe J, Kassam A, Da Silva VF and Lorimer IAJ (2013) PTEN loss represses glioblastoma tumor initiating cell differentiation via inactivation of Lgl1. Oncotarget, 4, 1266-1279

Daneshmand D, Hanson JEL, Nabavi M, Hilton JF, Vandermeer L, Kanji F, Dent SF, Clemons M, Lorimer IAJ (2012) Detection of PIK3CA mutations in breast cancer bone metastases, ISRN Oncology, 492578. Epub 2012 Aug 30

Brain and neuromuscular disease; Brain cancer; Cancer

Basic research; Cancer biotherapeutics; Cell therapy; Disease models; Molecular and cellular biology; Translational research