Dr. Mireille Khacho
Dr. Mireille Khacho
Assistant Professor, Department of Biochemistry, Microbiology and Immunology
Room: Roger Guindon Hall, Room 4171 (office), 4107 (lab)
Office: 613-562-5800 ext. 8278
Work E-mail: email@example.com
Unravel the mechanisms by which mitochondria regulate stem cell function and longevity in order to develop therapeutic strategies that enhance tissue regeneration during aging and degenerative diseases.
Mitochondria are essential organelles with a fundamental role in cellular metabolism. These dynamic organelles undergo constant fission and fusion events that dictate their overall morphology and bioenergetic status. Dysregulation of mitochondrial dynamics is an important pathogenic factor in many degenerative diseases and during aging, however, little is known regarding the effect this has on stem cell function and tissue regeneration. Our recent studies have uncovered a novel role for mitochondrial dynamics and function in the regulation of stem cell metabolism and fate decisions. These studies revealed that mitochondria orchestrate a nuclear transcriptional program through ROS-mediated retrograde signaling that regulates the self-renewal versus differentiation decisions of stem cells. Consequently, disruption of mitochondrial dynamics alters the metabolic and redox profile of stem cells and impairs their self-renewal and regenerative capacity. Based on these findings we propose that 1) mitochondria are a key regulatory point for the life-long maintenance and function of stem cells; and that 2) impaired mitochondrial function is an underlying factor in the functional and regenerative decline of muscle stem cells in muscle-related degenerative diseases and aging.
Our future studies will aim at elucidating the mechanisms by which mitochondrial dynamics and function control the metabolic profile, fate decisions and maintenance of muscle stem cells, during physiological and disease states, using metabolomic, transcriptomic and proteomic approaches. The long-term goal of this research program is to establish therapeutic strategies to modify mitochondrial dynamics and function in stems cells in order to restore the regenerative potential of tissues within the context of degenerative diseases and aging.
Students and Postdoctoral fellows interested in joining our dynamic lab and advancing in this exciting new research field are encouraged to contact Dr. Mireille Khacho
- Khacho M., Clark A., Svoboda, S.A., MacLaurin J.G., Lagace D.C., Park P.S. and Slack R.S. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. Human Molecular Genetics (2017). DOI: 10.1093/hmg/ddx217.
- Khacho M. & Slack R.S. Mitochondrial and ROS signaling coordinate stem cell fate decisions and life-long maintenance. Antioxidant and Redox Signaling (2017). DOI:10.1089/ars.2017.7228.
- Khacho M., Clark A., Svoboda, S.A., Azzi J., MacLaurin J.G., Meghaizel C., Sesaki H., Lagace D.C., Germain M., Harper M.E., Park P.S. and Slack R.S. Mitochondrial dynamics impact stem cell identity and fate decisions by regulating a nuclear transcriptional program. Cell Stem Cell 19(2):232-247 (2016).
- Audas T., Audas D.E., Jacob M.D., Ho D.J., Khacho M., Wang M., Perera J., Gardiner C., Bennett C., Head T., Kryvenko O.N., Jorda, M. Daunert S., Malhortra A., Trinkle-Mulcahy L., Gonzalgo M.L. and Lee S. Adaptation to stressors by systemic protein amyloidogenesis. Developmental Cell 39(2): 155-168 (2016).
- Khacho M., Tarabay M., Patten D., Khacho P., MacLaurin J., Guadagno J., Bergeron R., Cregan S.P., Harper M.E., Park D., Slack R.S. Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival. Nature Communications (2014) DOI.10.1038/ncomms4550.
- Patten D., Wong J., Khacho M., Soubannier V., Mailloux R.J., Pilon-Larose K., MacLaurin J.G., Park D.S., McBride H.M., Trinkle-Mulcahy L., Harper M.E., Germain M., Slack R.S. OPA1 senses metabolic changes through SLC25 family proteins to regulate mitochondrial function. EMBO J 33(22):2676-2691 (2014).