个人简介

Ph.D. (Doctor of Philosophy)

研究领域

Molecular Biology and Disease

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. The ER plays a vital role in many cellular processes, including calcium signaling lipid biosynthesis; and protein synthesis, folding, and post-translational modification. Most importantly, the ER can detect and integrate incoming signals, generate output signals in response to environmental changes, and can even modulate its own luminal dynamics. How the ER affects the balance between anti- versus pro-apoptotic signals, and therefore between adaptive and maladaptive cellular responses, remains a crucial question in pathophysiology and in cell biology. ER stress is associated with many severe human pathologies including heart disease, metabolic disorders, cancer and neuropathies. The multifunctional nature of the ER has enabled us to help identify the contribution of several ER associated proteins to the maintenance of ER homeostasis in health and disease. 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. Currently, the focus of our lab is on the role of ER associated molecular chaperones (calreticulin, calnexin and others) and ER stress in cardiac and nervous system physiology and pathophysiology. 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.

近期论文

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UBC9-dependent association between calnexin and protein tyrosine phosphatase 1B (PTP1B) at the endoplasmic reticulum. Lee D, Kraus A, Prins D, Groenendyk J, Aubry I, Liu WX, Li HD, Julien O, Touret N, Sykes BD, Tremblay ML, Michalak M. J Biol Chem. 2015 Feb 27;290(9):5725-38. doi: 10.1074/jbc.M114.635474. Epub 2015 Jan 13. Interplay between the oxidoreductase PDIA6 and microRNA-322 controls the response to disrupted endoplasmic reticulum calcium homeostasis. Groenendyk J, Peng Z, Dudek E, Fan X, Mizianty MJ, Dufey E, Urra H, Sepulveda D, Rojas-Rivera D, Lim Y, Kim do H, Baretta K, Srikanth S, Gwack Y, Ahnn J, Kaufman RJ, Lee SK, Hetz C, Kurgan L,Michalak M. Sci Signal. 2014 Jun 10;7(329):ra54. Disrupted WNT signaling in mouse embryonic stem cells in the absence of calreticulin. Groenendyk J, Michalak M. Stem Cell Rev. 2014 Apr;10(2):191-206. Calreticulin induces dilated cardiomyopathy. Lee D, Oka T, Hunter B, Robinson A, Papp S, Nakamura K, Srisakuldee W, Nickel BE, Light PE, Dyck JR, Lopaschuk GD, Kardami E, Opas M, Michalak M. PLoS One. 2013;8(2):e56387. doi: 10.1371/journal.pone.0056387. Epub 2013 Feb 20. Erratum in: PLoS One. 2013;8(11). Coping with endoplasmic reticulum stress in the cardiovascular system. Groenendyk J, Agellon LB, Michalak M. Annu Rev Physiol. 2013;75:49-67.