Autophagy and Apoptosis Crosstalk
Exploring the regulatory relationships between autophagy and apoptosis utilizing genetic, genomic, molecular and proteomic approaches in Drosophila and mammalian model systems.
|Project Leaders||Sharon Gorski|
|Project Co-Investigators||Gregg Morin|
InCell Analyzer LC3 Drosophila
The study of autophagy in human health is a new research field that has recently generated tremendous attention due to the recognition that autophagy is involved in multiple developmental processes and various human diseases including cancer. Autophagy is an evolutionary conserved mechanism that functions as an adaptive survival response to nutrient deprivation and other cellular stresses, though in some settings it can lead alternatively to cell death. Apoptosis, a well-characterized form of cell death, is another cellular process activated in response to stress. Recent studies indicate that a complex relationship exists between autophagy and apoptosis, and that the interplay between these two processes determines whether a cell will live or die. Since both autophagy and apoptosis are important for normal development and human disease pathogenesis, it is crucial to understand how they interact to determine these opposing cell fates.
The overarching objective of this project is to elucidate regulatory relationships between autophagy and apoptosis at the molecular level. Current avenues of investigation include determining the molecular mechanisms of caspase-mediated autophagy, identifiying factors involved in promoting a cell death versus cell survival role for autophagy, and exploring evolutionary conservation of autophagy-apoptosis relationships.
Recent Publications by our Research Team:
- Armstrong LJ and Gorski SM. "Breast Cancer and Autophagy" Chapter II in Breast Cancer: Causes, Diagnosis and Treatment, Nova Publishers 2010.
- Chittaranjan S, McConechy M, Hou YC, Freeman JD, DeVorkin L and Gorski SM. Steroid hormone control of cell death and cell survival: molecular insights using RNAi. Plos Genetics. 2009, 5(2) e/000379.
- Hannigan AM, Gorski SM. Macroautophagy: The key ingredient to a healthy diet? Autophagy. 2009 Feb 3;5(2): 140-51.Abstract
- Hou YC, Hannigan AM, Gorski SM. An executioner caspase regulates autophagy. Autophagy. 2009, May;5(4):530-3.Abstract
- Hou YC, Chittaranjan S, Gonzalez S, McCall K and Gorski SM. Effector caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster oogenesis. The Journal of Cell Biology. 2008, Sept. 22;182(6):1127-39.
- Qadir M, Kwok B, Dragowska WH, To KH, Le D, Bally MB, and Gorski SM. Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization. Breast Cancer Research and Treatment. 2008 Dec;112(3):389-403.Abstract
- Klionsky DJ, Abeliovich H, Agostinis P, Agrawal D….....Gorski SM et al… Guidelines for Monitoring Autophagy in Higher Eukaryotes. Autophagy 2008 Feb;4(2): 151-175. (multi-author/institution review)
- Copeland JM, Bosdet I, Guo M, Freeman JD, Guo M, Gorski SM* and Hay BA. Echninus, required for interommatidial cell sorting and cell death in the Drosophila pupal retina, encodes a protein with homology to ubiquitin-specific proteases. BMC Developmental Biology. 2007 Jul 5;7(1):82- . *Co-corresponding author
- Akdemir F, Farkas R, Chen P, Juhasz G, Medvedova L, Sass M, Wang L, Wang X, Chittaranjan S, Gorski SM, Rodriguez A, Abrams JM. Autophagy occurs upstream of or parallel to the apoptosome during histolytic cell death. Development. 2006 Apr;133(8): 1457-1465.
For all project related inquires please contact us.
Stephanie McInnis, Project Manager
Genome Sciences Centre, BC Cancer Agency
Phone: 604-675-8000 x 7965