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Marek Michalak

Michalak.jpg
Distinguished University Professor
Ph.D., Nencki Institute
M.Sc. University of Warsaw
 
 
Department of Biochemistry
Faculty of Medicine & Dentistry
University of Alberta
355 Medical Sciences Building
Edmonton, Alberta, Canada  T6G 2H7
 
Tel: 780.492.2256
Lab Tel: 780.492.3481
Fax:  780.492.0886
 
Research:
Our lab studies the structure and function of endoplasmic reticulum (ER) membranes and the role of this membrane system in the control of intracellular signalling, communication with other intracellular organelles, regulation
Our lab studies the structure and function of endoplasmic reticulum (ER) membranes and the role of this membrane system in the control of intracellular signalling, communication with other intracellular organelles, regulation of protein synthesis and folding, modulation of gene expression and calcium homeostasis. We discovered that ER resident chaperones play critical roles in cardiac development and pathophysiology of the mature heart. The proteins are also key in specific neuropathies. Our long-term goal is to understand ER stress and ER signaling events responsible for the activation and maintenance of intracellular pathways affecting cardiac or neuronal physiology and pathology, and to use this information to devise pharmacological and genetic therapies for the treatment of human disease.
 
Here are a few examples of research projects currently being pursued in our lab:
 
Modulators of ER stress
We have identified several cellular proteins that regulate ER stress responses and the unfolded protein response (UPR), including ER luminal resident chaperones and folding enzymes. We are pursuing a variety of strategies to use this information to manipulate ER stress pathways and to uncover additional regulators of ER stress.
 
Calreticulin, ER resident proteins and cardiac physiology.
We apply gene knockout and transgenic techniques to understand the role of ER proteins and the ER luminal environment in embryogenesis and congenital pathologies. We are investigating the contribution of calreticulin and other ER resident proteins to cardiac pathology including cardiac hypertrophy and heart failure.
 
ER calcium homeostasis
Intracellular Ca2+ is an important second messenger. Ca2+ is released from the ER into the cytoplasm and the loss of ER Ca2+ stores necessitates refilling via a process known as store-operated Ca2+ entry (SOCE). We are interested in understanding the role of ER luminal environment in regulation of ER-dependent Ca2+ signaling and its role in human pathology.
 
ER chaperones and energy metabolism
Disrupted ER homeostasis due to loss of ER chaperones may lead to dysregulation of energy metabolism. We are interested in the mechanisms responsible for ER-dependent modulation of energy metabolism with a special emphasis on the role of ER associated molecular chaperones.
 
Deciphering a role of ER chaperones in neuropathies
We discovered that calnexin-deficient mice develop a specific neuropathy, dysmyelination and impaired motor function. We are interested in understanding the role of calnexin and ER stress in the pathology of the nervous system with a special emphasis on human neuropathies such as Multiple Sclerosis, amyotrophic lateral sclerosis (ALS) and myelin diseases.
 
Lab Members:
Monika Dabrowska, Technical
Elzbieta Dudek, Postdoctoral Fellow
Jody Groenendyk, Research Associate
Joanna Jung, Postdoctoral Fellow
Daniel Prins, Graduate Student
Alison Robinson, Technical
Wen-An (Jennifer) Wang, Graduate Student
Qian Wang, Graduate Student
 
 
Selected Publications:
Groenendyk, J., Peng, Z., Dudek, E., Fan, X., Mizianty, M.J., Dufey, E., Urra, H., Sepulveda, D., Rojas-Rivera, D., Yunki, L., Kim, D.H., Baretta, K., Srikanth, S., Gwack, G., Ahnn, J., Kaufman, R.J., Lee, S-K., Hetz, C., Kurgan, L. and Michalak M. 2014. Interplay between PDIA6 and miR-322 controls adaptive response to disrupted endoplasmic reticulum calcium homeostasis. Science Signaling(329): ra54
 
Lee, D., Oka, T., Hunter, B., Robinson, A., Papp, S., Nakamura, K., Srisakuldee, W., Nicke, B.E., Light, P.E., Dyck, J.R.B., Lopaschuk, G.L., Kardami, E., Opas, M. and Michalak, M. 2013. Calreticulin induces dilated cardiomyopathy. PLoS ONE,8:e56387
 
Groenendyk, J., Agellon, L.B. and Michalak, M. 2013. Coping with endoplasmic reticulum stress in the cardiovascular system. Annu. Rev. Physiol75: 49-67
 
Millott, R., Dudek, E. and Michalak, M. 2012. The endoplasmic reticulum in cardiovascular health and disease. Can. J. Physiol. Pharmacol90: 1209-1217
 
Li H-D, Liu W-X and Michalak M. 2011. Enhanced clathrin-dependent endocytosis in the absence of calnexin. PLoS ONE 6:e21678
 
Groenendyk J and Michalak M. 2011. A Genome-wide siRNA screen identifies novel phospho-enzymes affecting Wnt/?-catenin signaling in mouse embryonic stem cells. Stem Cell Rev. Rep. 7:910-926
 
Jung J, Coe H and Michalak M. 2011. Specialization of endoplasmic reticulum chaperones for the folding and function of myelin glycoproteins P0 and PMP22.FASEB J. 25:3929-3937
 
Prins D, Groenendyk J, Touret N and Michalak M. 2011. Endoplasmic reticulum luminal environment-dependent regulation of STIM1 and capacitative Ca2+ entry. EMBO Rep. 12:1182-1188