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

Cancer Res. 2019 Sep 26;:
Manem VS, Lambie M, Smith I, Smirnov P, Kofia V, Freeman M, Koritzinsky M, Abazeed ME, Haibe-Kains B, Bratman SV
Commun Biol. 2019;2:192
Shehata M, Kim H, Vellanki R, Waterhouse PD, Mahendralingam M, Casey AE, Koritzinsky M, Khokha R
Nat Commun. 2019 Jan 17;10(1):278
Guo H, Ci X, Ahmed M, Hua JT, Soares F, Lin D, Puca L, Vosoughi A, Xue H, Li E, Su P, Chen S, Nguyen T, Liang Y, Zhang Y, Xu X, Xu J, Sheahan AV, Ba-Alawi W, Zhang S, Mahamud O, Vellanki RN, Gleave M, Bristow RG, Haibe-Kains B, Poirier JT, Rudin CM,...
Mol Cancer Res. 2018 Feb 16;:
Ding M, van der Kwast TH, Vellanki RN, Foltz WD, McKee TD, Sonenberg N, Pandolfi PP, Koritzinsky M, Wouters BG
Int J Cancer. 2018 Feb 08;:
Lecavalier-Barsoum M, Chaudary N, Han K, Koritzinsky M, Hill R, Milosevic M
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

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