Logue Lab

Research Focus

Cell stress responses are highly conserved signaling pathways triggered when cells encounter stressful conditions such as low oxygen or nutrient deprivation. One such pathway – the Unfolded Protein Response (UPR) – is activated upon the accumulation of unfolded proteins within the Endoplasmic Reticulum (ER). The UPR is controlled by three transmembrane receptors anchored on the ER – IRE1, PERK and ATF6. In nonstressed cells each receptor is maintained in an “off” state by binding to Grp78 (an ER chaperone protein). Upon accumulation of unfolded proteins (ER stress) Grp78 dissociates from IRE1, PERK and ATF6 permitting their activation and triggering downstream signaling pathways which work in concert to lower levels of unfolded proteins and restore ER homeostasis.


Schematic representation of the Unfolded Protein Response (Madden E, Logue SE, Healy SJ, Maine S and Samali A. Biology of the Cell, 2019)

Our current understanding of UPR activation and its influence on cellular signaling networks is consigned to within a cell. Recent evidence indicates, in addition to influencing internal signaling networks (so called intrinsic effects), UPR activation can also impact on a cell’s surrounding microenvironment. The finding that internal UPR signaling can be associated with extrinsic effects is a new area of UPR research. Currently, it is not understood how cell extrinsic UPR effects are communicated to surrounding cells, nor is the outcome of it on cellular signaling networks/biological responses within recipient cells.


The objectives of my research program are:

1. Identify how internal UPR signaling pathways promote extrinsic UPR effects

2. Understand how extrinsic UPR effects are communicated to surrounding cells

3. Identify the biological impact of extrinsic UPR effects on the surrounding microenvironment


Interested in our research?

We are always on the look out for enthusiastic, motivated grad students and postdocs with an interest in cell stress responses. Positions are currently available please email susan.logue@umanitoba.ca for further information.


Selected Publications

Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances response to chemotherapy.
Logue SE, McGrath EP, Cleary P, Greene S, Mnich K, Almanza A, Chevet E, Dwyer RM, Oommen A, Legembre P, Godey F, Madden EC, Leuzzi B, Obacz J, Zeng Q, Patterson JB, Jäger R, Gorman AM, Samali A.
Nature Communications. 2018 Aug 15;9(1):3267

RIP2 enhances cell survival by activation of NF-ĸB in triple negative breast cancer cells. Jaafar R, Mnich K, Dolan S, Hillis J, Almanza A, Logue SE, Samali A, Gorman AM. Biochem Biophys Res Commun. 2018 Feb 26;497

Saveljeva S, Cleary P, Mnich K, Ayo A, Pakos-Zebruka K, Patterson J, Logue SE*, Samali A*. Endoplasmic Reticulum Stress-mediated Induction of Sestrin 2 potentiates cell survival.
Oncotarget. 2016. 15;7(11):12254-66. *Joint Corresponding author

Chonghaile TN, Gupta S, Mohan, J, Szegezdi S, Logue SE*, Samali A*. BCL-2 modulates the unfolded protein response by enhancing splicing of X-box binding protein-1. BBRC. 2015 *Joint Corresponding author

Deegan S*, Saveljeva S*, Logue SE*, Pakos-Zebrucka K, Gupta S, Vandenabeele P, Bertrand MJ, Samali A. Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under ER stress conditions.
Autophagy. 2014;10(11):1921-36. *Joint First Author

Cullen SP, Henry CM, Kearney CJ, Logue SE, Feoktistova M, Tynan GA, Lavelle EC, Leverkus M, Martin SJ. Fas/CD95-Induced Chemokines can Serve as ‘Find-Me’ Signals for Apoptotic Cells.
Molecular Cell. 2013 Mar 28;49(6):1034-48

For a full publication list please click here