Marianne Koritzinsky

Tumour hypoxia (poor oxygenation) limits the efficacy of radio- and chemotherapy and promotes a more malignant phenotype. Our aim is to identify novel treatment strategies to mitigate the adverse effects of tumour hypoxia. To this end, we aim to better understand how hypoxia regulates signalling and gene expression that alters metabolism, cancer cell survival and metastasis.

Specific projects include:

1) Regulation of protein folding and secretion
Hypoxia increases the secretion of factors that stimulate blood vessel formation, migration and invasion, which promotes tumour growth and malignant behaviour. These factors have to mature and fold in the endoplasmic reticulum prior to secretion. We aim to identify the mechanisms that support folding and maturation in hypoxia, and to target these mechanisms to mitigate hypoxia-induced protein secretion.

2) Regulation and reprogramming of tumour metabolism
Mutations in some cancer genes cause cells to alter their metabolism. We aim to understand how such genes alter metabolism, how this affects their response to hypoxia and how these changes can be exploited therapeutically. We also use pharmacological agents to reprogram cancer metabolism in ways that decreases tumour hypoxia and promotes the response to conventional cancer treatment.
 

Related Links

PLoS One. 2016;11(12):e0165214
Chowdhury S, Yung E, Pintilie M, Muaddi H, Chaib S, Yeung M, Fusciello M, Sykes J, Pitcher B, Hagenkort A, McKee T, Vellanki R, Chen E, Bristow RG, Wouters BG, Koritzinsky M
Adv Drug Deliv Rev. 2016 Oct 19;:
Rey S, Schito L, Koritzinsky M, Wouters BG
CBE Life Sci Educ. 2016;15(1):le1
Koritzinsky M, Koch CA, Riley B, Beauchemin N, Johnston G, Johnston M, Koropatnick J, Loiselle CG, Maslowska M, McCormick C, Miller WH, Mulligan L, Tsao MS
Semin Radiat Oncol. 2015 Oct;25(4):260-72
Hill RP, Bristow RG, Fyles A, Koritzinsky M, Milosevic M, Wouters BG
Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):454-64
Koritzinsky M
Cancer Res. 2015 Aug 21;
Hunter FW, Young RJ, Shalev Z, Vellanki RN, Wang J, Gu Y, Joshi N, Sreebhavan S, Weinreb I, Goldstein DP, Moffat J, Ketela T, Brown KR, Koritzinsky M, Solomon B, Rischin D, Wilson WR, Wouters BG
Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10774-9
Ravishankar B, Liu H, Shinde R, Chaudhary K, Xiao W, Bradley J, Koritzinsky M, Madaio MP, McGaha TL
Nat Commun. 2014;5:5203
van den Beucken T, Koch E, Chu K, Rupaimoole R, Prickaerts P, Adriaens M, Voncken JW, Harris AL, Buffa FM, Haider S, Starmans MH, Yao CQ, Ivan M, Ivan C, Pecot CV, Boutros PC, Sood AK, Koritzinsky M, Wouters BG
J Enzyme Inhib Med Chem. 2014 Oct 27;:1-33
Pettersen EO, Ebbesen P, Gieling RG, Williams KJ, Dubois L, Lambin P, Ward C, Meehan J, Kunkler IH, Langdon SP, Ree AH, Flatmark K, Lyng H, Calzada MJ, Peso LD, Landazuri MO, Görlach A, Flamm H, Kieninger J, Urban G, Weltin A, Singleton DC, Haider S,...
Mol Cancer Res. 2014 Oct;12(10):1407-15
Chan N, Ali M, McCallum GP, Kumareswaran R, Koritzinsky M, Wouters BG, Wells PG, Gallinger S, Bristow RG

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Assistant Professor, Department of Radiation Oncology, University of Toronto
Member, Institute of Medical Science, University of Toronto