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Lunenfeld-Tanenbaum Research Institute,
Sinai Health
600 University Avenue
Toronto Ontario
M5G 1X5
Tel.:416-586-8888
ext.4183
Dr. Diane L. Haakonsen
INVESTIGATOR
Dr. Diane Haakonsen is an Investigator at the Lunenfeld-Tanenbaum Research Institute, Sinai Health, and an Assistant Professor in the Department of Molecular Genetics at the University of Toronto.
Her research focuses on the regulation of cellular stress signaling pathways activated in response to harmful situations such as heat, toxins, pathogens—including viruses and bacteria—and nutrient shortages. These responses can become hijacked in disease to fuel its progression, as happens in cancer and neurodegenerative disorders. Understanding how stress responses are regulated in both healthy and diseased cells is key to identifying new pathways and drug targets for therapeutic strategies.
Dr. Haakonsen’s research has revealed that stress responses must be actively turned off when their job is done, and that failure to do so can be highly detrimental. While much work has been done to understand how the appropriate stress responses are activated when needed, the brakes that silence them at the right time are not known and represent an interesting new avenue towards more effective treatments. Her focus now is to identify the mechanisms that turn off stress responses and how a failure to do so can lead to disease, including neurodegeneration.
Dr. Haakonsen was most recently a Helen Hay Whitney Postdoctoral Fellow at the University of California at Berkeley under the supervision of Dr. Michael Rapé. She obtained her PhD in Microbiology from the Massachusetts Institute of Technology under the supervision of Dr. Michael Laub.
At a Glance
- Investigator at the Lunenfeld-Tanenbaum Research Institute.
- Applies a multidisciplinary approach, combining genetic screens, cellular biology, and biochemical and structural characterization to determine how stress responses are turned off in health and disease.
- Awarded the UC Berkeley Molecular and Cell Biology Outstanding Postdoc Award for academic achievements, leadership and service.
Major Research Activities
Dr. Haakonsen’s ongoing research aims to reveal the mechanisms involved in cellular stress response termination. In particular she is focusing on:
- Having identified the SIFI complex, a large ubiquitin ligase as a new regulator of the integrated stress response (ISR) activated by mitochondrial defects, we are now pursuing the structure-function analysis of SIFI to understand how it works at the molecular level.
- Our work on the SIFI complex and HRI has revealed that chronic activation of the ISR is detrimental. We are now investigating the mechanisms by which cells silence the ISR activated by other ISR kinases when the stress signal is no longer active.
We found that silencing of the ISR dramatically improved survival in cells experiencing mitochondrial stress, even when the stress signal is still present. This suggests that in addition to the stress itself, prolonged stress response activation may contribute to neurodegenerative diseases caused by mitochondrial stress, which we are now investigating in laboratory models.
