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Edmond Chan PhD
 Edmond Chan
Position(s)
Assistant Professor
Contact Info
Room 627 Botterell Hall
613 533 6946

Autophagy as a metabolic homeostasis mechanism

The metabolic status of a cell guides critical decisions such as growth, death or differentiation. We aim to understand the fundamental signalling mechanisms that allow mammalian cells to adapt following external stress, focussing on the autophagy pathway.

Autophagy is the main route for channelling cellular material to the lysosome for degradation and internal recycling.   By this route, autophagy serves a critical role for maintaining metabolic homeostasis and we are interested in 2 particular contexts: normal cellular aging and cancer cell survival. Cancer cells are distinct for their re-programmed metabolic profile that features high catabolism of glucose and amino acids. Therefore, we have long been interested in the mechanisms linking these cellular nutrients to autophagy in normal and cancer cells.. 

Sponsors:
We are currently supported by a Natural Sciences and Engineering Research Council of Canada (NSERC/CRSNG) Discovery grant.  

Publications

Edmond Chan: Google Scholar

Radhi, O. A., S. Davidson, F. Scott, R. X. Zeng, D. H. Jones, N. C. O. Tomkinson, J. Yu, and E. Y. W. Chan. (2019)  Inhibition of the Ulk1 Protein Complex Suppresses Staphylococcus-Induced Autophagy and Cell Death.  J Biol Chem. http://dx.doi.org/10.1074/jbc.RA119.008923.

Anwar, T., X. Liu, T. Suntio, A. Marjamaki, J. Biazik, E. Y. W. Chan, M. Varjosalo, and E. L. Eskelinen. (2019)  Er-Targeted Beclin 1 Supports Autophagosome Biogenesis in the Absence of Ulk1 and Ulk2 Kinases.  Cells 8. http://dx.doi.org/10.3390/cells8050475

Nwadike C., Williamson L.E., Gallagher L.E. , Guan J.-L., Chan E.Y.W. (2018) AMPK inhibits ULK1-dependent autophagosome formation and lysosomal acidification via distinct mechanisms. Mol Cell Biol.  38(10): e00023-18 https://mcb.asm.org/content/38/10/e00023-18.long

Gallagher, L. E., Radhi, O. A., Abdullah, M. O., McCluskey, A. G., Boyd, M. and Chan, E. Y. W. (2017). Lysosomotropism depends on glucose: a chloroquine resistance mechanism. Cell Death Dis, 8(8), e3014. doi:10.1038/cddis.2017.416.  

Mitchell, R., Hopcroft, L. E. M., Baquero, P., Allan, E. K., Hewit, K., James, D., Hamilton, G., Mukhopadhyay, A., O'Prey, J., Hair, A., Melo, J. V., Chan, E., Ryan, K. M., Maguer-Satta, V., Druker, B. J., Clark, R. E., Mitra, S., Herzyk, P., Nicolini, F. E., Salomoni, P. and Helgason, G. V. (2017). Targeting BCR-ABL-Independent TKI Resistance in Chronic Myeloid Leukemia by mTOR and Autophagy Inhibition. J Natl Cancer Inst. doi:10.1093/jnci/djx236.   pubmed/29165716

Gallagher, L., Williamson, L. and Chan, E. (2016). Advances in Autophagy Regulatory Mechanisms. Cells, 5(2), 24. doi:10.3390/cells5020024.   www.mdpi.com/2073-4409/5/2/24

Karvela, M., Baquero, P., Kuntz, E. M., Mukhopadhyay, A., Mitchell, R., Allan, E. K., Chan, E., Kranc, K. R., Calabretta, B., Salomoni, P., Gottlieb, E., Holyoake, T. L. and Helgason, G. V. (2016). ATG7 regulates energy metabolism, differentiation and survival of Philadelphia-chromosome-positive cells. Autophagy, 12(6), 936-948. doi:10.1080/15548627.2016.1162359.   pubmed/27168493

Klionsky, D. J., et al. (2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12(1), 1-222. doi:10.1080/15548627.2015.1100356.  

Gallagher, L. E. and Chan, E. Y. (2013). Early signalling events of autophagy. Essays Biochem, 55, 1-15. doi:10.1042/bse0550001.  

McAlpine, F., Williamson, L. E., Tooze, S. A. and Chan, E. Y. (2013). Regulation of nutrient-sensitive autophagy by uncoordinated 51-like kinases 1 and 2. Autophagy, 9(3), 361-373. doi:10.4161/auto.23066.   https://www.ncbi.nlm.nih.gov/pubmed/23291478

Mleczak, A., Millar, S., Tooze, S. A., Olson, M. F. and Chan, E. Y. (2013). Regulation of autophagosome formation by Rho kinase. Cell Signal, 25(1), 1-11. doi:10.1016/j.cellsig.2012.09.010.  

Tonelli, F., Alossaimi, M., Williamson, L., Tate, R. J., Watson, D. G., Chan, E., Bittman, R., Pyne, N. J. and Pyne, S. (2013). The sphingosine kinase inhibitor 2-(p-hyroxyanilino)-4-(p-chlorophenyl)thiazole reduces androgen receptor expression via an oxidative stress-dependent mechanism. Br J Pharmacol, 168(6), 1497-1505. doi:10.1111/bph.12035.  

Watson, D. G., Tonelli, F., Alossaimi, M., Williamson, L., Chan, E., Gorshkova, I., Berdyshev, E., Bittman, R., Pyne, N. J. and Pyne, S. (2013). The roles of sphingosine kinases 1 and 2 in regulating the Warburg effect in prostate cancer cells. Cell Signal, 25(4), 1011-1017. doi:10.1016/j.cellsig.2013.01.002.  

Chan, E. Y. (2012). Regulation and function of uncoordinated-51 like kinase proteins. Antioxid Redox Signal, 17(5), 775-785. doi:10.1089/ars.2011.4396.