Canada Research Chair in Neurodegeneration and Stem Cell Regeneration
PH.D. University of Ottawa
B.Sc. Cornell University
Office: Robarts Research Institute, Room 3244
p. 519.663.5777 x. 24134
Visit: Dr.Cregan at Robarts Research Institute
See Publications by Sean Cregan on PubMed
Apoptosis is known to play a critical role in the normal development of the nervous system. However, its inappropriate activation in mature neurons has been implicated as a major contributing factor in the neurological dysfunction associated with a number of neurodegenerative diseases as well as following brain or spinal cord injury. The laboratory of Dr. Cregan is investigating the molecular mechanisms that regulate apoptotic cell death in the affected nervous system. Dr. Cregan has demonstrated that both caspases and caspase-independent death effectors such as Apoptosis Inducing Factor (AIF) contribute to the neuronal cell death response. Furthermore, he has determined that activation of both of these pathways is regulated by the pro-apoptotic Bcl-2 family protein Bax. The laboratory is currently examining the role of P53 and other injury inducible factors in the regulation of Bax activation using in vitro and in vivo models of neuronal injury.
Dr. Cregan's laboratory is also studying the molecular signaling pathways involved in the regulation of apoptosis in neural stem cells. The discovery of stem cells within the brain has lead to much excitement as it is believed that these cells have the potential to regenerate damaged or diseased nervous tissue. However, the propensity of activated neural stem cells to undergo apoptosis has posed a major impediment to the success of such cell replacement therapies. Dr. Cregan's laboratory has developed a trophic factor deprivation model to study apoptosis in neural precursor cells. This research will lead to the identification of critical components of the apoptotic pathway in neural precursor cells which they will exploit to facilitate regeneration in the injured and diseased nervous system.
Guadagno J, Xu K, Karajgikar M, Brown A, and Cregan SP (2013), Microglia derived TNF-alpha induces apoptosis in neural precursor cells via transcriptional activation of the Bcl-2 family member Puma. Cell Death & Disease Mar 14;4
Galehdar Z, Swan P, Fuerth B, Callaghan S, Park DS and Cregan SP (2010), Neuronal apoptosis induced by ER stress is regulated by ATF4-CHOP mediated induction of the BH3-only member PUMA.
J Neurosci 30(50):16938-48.
Steckley D, Karajgikar M, Dale LB, Fuerth B, Swan P, Drummond-Main C, Poulter MO, Ferguson SS, Strasser A, and Cregan SP (2007), PUMA is a dominant regulator of oxidative stress induced Bax activation and neuronal apoptosis. J. Neurosci. 27(47):12989-12999.
SP Cregan, N Arbour, JG MacLaurin, SM Callaghan, A Fortin, ECC Cheung, AE Mackenzie, DS Park, and RS Slack (2004), P53 activation domain 1 is essential for PUMA upregulation and p53-mediated neuronal cell death. J Neurosci. 24(44), 10003-10012.