Natasha Chang

McGill University | McGill · Department of Biochemistry

Autophagy is a fundamental cell survival mechanism that allows cells to adapt to metabolic stress through the degradation and recycling of intracellular components to generate macromolecular precursors and produce energy. The autophagy pathway is critical for development, maintaining cellular and tissue homeostasis, as well as immunity and preventi...

Asymmetrically dividing muscle stem cells in skeletal muscle give rise to committed cells, where the myogenic determination factor Myf5 is transcriptionally activated by Pax7. This activation is dependent on Carm1, which methylates Pax7 on multiple arginine residues, to recruit the ASH2L:MLL1/2:WDR5:RBBP5 histone methyltransferase complex to the pr...

Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells inc...

The outstanding regenerative capacity of skeletal muscle is attributed to the resident muscle stem cell termed satellite cell. Satellite cells are essential for skeletal muscle regeneration as they ultimately provide the myogenic precursors that rebuild damaged muscle tissue. Satellite cells characteristically are a heterogeneous population of stem...

Pax7 is a nodal transcription factor that is essential for regulating the maintenance, expansion, and myogenic identity of satellite cells during both neonatal and adult myogenesis. Deletion of Pax7 results in loss of satellite cells and impaired muscle regeneration. Here, we show that ectopic expression of the constitutively active intracellular d...

Muscle stem cells, also known as satellite cells, are responsible for the regenerative capacity of adult muscle tissue in response to stress and injury. Upon regenerative stimuli, satellite cells are activated and undergo myogenic commitment. Myogenic progenitors, which are termed myoblasts, undergo rapid proliferation, propagation, and differentia...

The intentional pharmacological manipulation of myogenesis is an important technique for understanding the underlying mechanisms of muscle differentiation and disease etiology. Using the pharmacological agent metformin as an example molecule, we present a systematic approach to examine the impact of pharmacological agents on the myogenic program. T...

Autophagy is a critical cellular program that is necessary for cellular survival and adaptation to nutrient and metabolic stress. In addition to homeostatic maintenance and adaptive response functions, autophagy also plays an active role during development and tissue regeneration. Within the neural system, autophagy is important for stem cell maint...

Fluorescence microscopy is a powerful tool enabling the visualization of protein localization within cells. In this article, we outline an automated and non‐biased way to detect and quantify subcellular particles using immunocytochemistry, fluorescence microscopy, and the program CellProfiler. We discuss the examination of two types of subcellular...

Duchenne muscular dystrophy (DMD) is a devastating and debilitating muscle degenerative disease affecting 1 in every 3,500 male births worldwide. DMD is progressive and fatal; accumulated weakening of the muscle tissue leads to an inability to walk and eventual loss of life due to respiratory and cardiac failure. Importantly, there remains no effec...

EGFRvIII-STAT3 signaling is important in glioblastoma pathogenesis. Here, we identified the cytokine receptor OSMR as a direct target gene of the transcription factor STAT3 in mouse astrocytes and human brain tumor stem cells (BTSCs). We found that OSMR functioned as an essential co-receptor for EGFRvIII. OSMR formed a physical complex with EGFRvII...

EGFRvIII/STAT3 signaling plays a significant role in glioblastoma pathogenesis. Here, we identify the cytokine receptor OSMR as a direct target gene of the transcription factor STAT3 in mouse astrocytes and human brain tumor stem cells (BTSCs). Strikingly, OSMR forms a receptor complex with EGFRvIII in human BTSCs and mouse astrocytes. Accordingly,...

Significance Satellite cells form the resident stem cell population in adult skeletal muscle, providing the foundation for postnatal growth and repair of this tissue. Satellite cell self-renewal is maintained by the paired-box transcription factor Pax7, suggesting that this protein is a key determinant in managing cell fate decisions for this niche...

Diminished regenerative capacity of skeletal muscle occurs during adulthood. We identified a reduction in the intrinsic capacity of mouse adult satellite cells to contribute to muscle regeneration and repopulation of the niche. Gene expression analysis identified higher expression of JAK-STAT signaling targets in 3-week-old relative to 18-month-old...

Muscle disorders are debilitating and their associated symptoms dramatically impact the quality of patients' lives. Characteristically, pathologies of the muscle tissue overwhelm the intrinsic capacity of muscles to regenerate, causing muscle wasting and the loss of muscle function. Thus, not only are myopathies diseases of the myofibers but they a...

Wnt signaling has essential roles during embryonic development and tissue homoeostasis. Wnt proteins are post-translationally modified and the attachment of a palmitate moiety at two conserved residues is believed to be a prerequisite for the secretion and function of Wnt proteins. Here we demonstrate that a mammalian Wnt protein can be fully funct...

The formation of skeletal muscle is a tightly regulated process that is critically modulated by Wnt signaling. Myogenesis is dependent on the precise and dynamic integration of multiple Wnt signals allowing self-renewal and progression of muscle precursors in the myogenic lineage. Dysregulation of Wnt signaling can lead to severe developmental defe...

CISD2, an ER BCL2-associated autophagy regulator also known as NAF-1, is responsible for the human degenerative disorder Wolfram Syndrome 2. In order to interrogate the physiological role of CISD2 we generated and characterized the Cisd2 gene deletion in mice. Cisd2 null mice manifest significant degeneration in skeletal muscle tissues, which is ac...

Nutrient-deprivation autophagy factor-1 (NAF-1) was identified as an endoplasmic reticulum (ER) BCL-2-interacting protein, which functions to mediate the ability of ER BCL-2 to antagonize Beclin 1-dependent autophagy and depress ER calcium stores. In humans, a point mutation in Naf-1 (synonyms: Cisd2, Eris, Miner1 and Noxp70) is responsible for the...

Dynamic structural and functional liaisons between mitochondria and the endoplasmic reticulum (ER) support a wide range of cell functions, including the ability of the cell to kill itself by apoptosis. A new study in this issue of The EMBO Journal sheds light on how these interactions regulate Bax/Bak-driven cell death within the complex milieu of...

In addition to mitochondria, BCL-2 is located at the endoplasmic reticulum (ER) where it is a constituent of several distinct complexes. Here, we identify the BCL-2-interacting protein at the ER, nutrient-deprivation autophagy factor-1 (NAF-1)-a bitopic integral membrane protein whose defective expression underlies the aetiology of the neurodegener...

Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well...

Autophagy and apoptosis are two major signaling pathways employed by the cell in response to various stress-induced signals in order to manage such stress and ultimately to determine cellular survival or death. Central to the regulation of both pathways is the BCL-2 protein family. At the endoplasmic reticulum (ER) the pro-survival BCL-2 protein ta...