Cells are often compared to miniature cities, each with its own infrastructure. The nucleus functions like city hall, mitochondria act as power plants and the endoplasmic reticulum (ER) serves as the industrial hub where proteins are produced and folded. When that system falters, the results can threaten cell survival.
Susan Logue, associate professor in the department of human anatomy and cell science at the U of M and Canada research chair in cell stress and inflammation, studies what happens when the ER comes under strain. Her lab focuses on a cellular emergency system called the unfolded protein response (UPR).
“The job of the unfolded protein response is to try and help reduce the level of unfolded proteins and to allow the endoplasmic reticulum to go back to normal,” Logue said. In healthy cells, this response switches on briefly to support ER function. However, in diseased cells, particularly cancer cells, the same process can be hijacked to promote the survival and growth of the cancer cells.
One area where this is especially relevant is triple negative breast cancer, an aggressive form of the disease that lacks targeted therapies. “Unlike many forms of breast cancer, there are few targeted therapies for triple negative breast cancer,” Logue explained. “So, it’s very important that we come up with new ways to help treat this disease.”
Her lab is investigating whether elements of the UPR could provide such a pathway. By studying the ER’s stress response in cancer cells, researchers hope to identify vulnerabilities that could be targeted with new drugs.
Much of the team’s work focuses on “three central receptors or ‘controllers’ called IRE1, PERK and ATF6.” These proteins act as control points, managing how cells respond when protein folding goes awry. “There’s been a lot of time and money spent on trying to come up with drugs to switch off IRE1, PERK and ATF6,” Logue said. One drug that inhibits IRE1 has already shown promise in preclinical models, especially when combined with chemotherapy.
Her lab recently asked what happens when one of these pathways is shut down. Their findings, published in Cell Death and Disease, revealed that inhibiting IRE1 also reduced PERK expression. This suggested that the pathways communicate more closely than previously thought, and that blocking one could weaken another. The group is now expanding this work. Early experiments suggest ATF6 also interacts with IRE1, deepening the picture of how these signalling systems cooperate under stress. Logue’s team is developing breast cancer cell lines that can switch parts of the UPR on or off, allowing them to study how these changes affect cancer cell growth, cell mobility and drug resistance.
While her lab does not design therapies directly, the goal is to provide the knowledge that others can build on.
She emphasized the importance of research as a team effort. Advances in medicine are often the result of many labs contributing different pieces of the puzzle over years of work.
“Aside from scientific findings, I also want my lab to be a productive and supportive training ground offering students the opportunity to gain research skills that they can take forward in their own careers,” she said.
For students considering research, Logue’s advice is straightforward — “The only real way to know if research is something for you is to get into a lab and try it out.”
Logue also highlighted the intricacy of cell biology. “What I really loved about cell signalling was [that] it’s like a game of chess. You make one move, the cell makes another move,” she said. The challenge, she noted, is part of what makes the work rewarding.
By decoding how cells respond to stress, Logue and her team are helping lay the groundwork for treatments that could one day improve outcomes for breast cancer patients.
