A5076605314- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Cancer-related gene regulation
- RNA Research and Splicing
- Neuropeptides and Animal Physiology
- Cancer, Stress, Anesthesia, and Immune Response
- Algal biology and biofuel production
- RNA Interference and Gene Delivery
- Amino Acid Enzymes and Metabolism
- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- Ubiquitin and proteasome pathways
- Herpesvirus Infections and Treatments
- Cancer-related molecular mechanisms research
- Cellular transport and secretion
- Micro and Nano Robotics
- Cancer Cells and Metastasis
- Signaling Pathways in Disease
- Chemokine receptors and signaling
- interferon and immune responses
- Photoreceptor and optogenetics research
University of Guelph
2014-2024
Concordia University
2007-2018
University of Ottawa
2012-2014
The nucleolus is a plurifunctional organelle in which structure and function are intimately linked. Its structural plasticity has long been appreciated, particularly response to transcriptional inhibition other cellular stresses, although the mechanism physiological relevance of these phenomena unclear. Using MCF-7 mammalian cell lines, we describe functional adaptation nucleolus, triggered by heat shock or acidosis, that depends on expression ribosomal intergenic spacer noncoding RNA (IGS...
Abstract Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast NANOG , SNAIL NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), translation subset these stimulated under hypoxia. The accumulation the corresponding proteins induces plasticity “fate-switching” toward stem cell-like phenotypes....
Organelles are intracellular compartments which themselves compartmentalized. Biogenic and metabolic processes localized to specialized domains or microcompartments enhance their efficiency suppress deleterious side reactions. An example of intra-organellar compartmentalization is the pyrenoid in chloroplasts algae hornworts. This microcompartment enhances photosynthetic CO2-fixing activity Calvin-Benson cycle enzyme Rubisco, suppresses an energetically wasteful oxygenase mitigates limiting...
Abstract Many proteins of the photosynthesis complexes are encoded by genome chloroplast and synthesized bacterium-like ribosomes within this organelle. To determine where for de novo assembly repair photosystem II (PSII) in Chlamydomonas reinhardtii, we used fluorescence situ hybridization, immunofluorescence staining, confocal microscopy. These locations were defined as having colocalized mRNAs encoding PSII subunits translation machinery specifically under conditions subunit synthesis....
The compartmentalization of eukaryotic cells requires that newly synthesized proteins be targeted to the compartments in which they function. In chloroplasts, a few thousand function photosynthesis, expression chloroplast genome, and other processes. Most are cytoplasm, imported, then specific compartment. remainder encoded by within organelle, mechanisms only beginning elucidated. We used fluorescence confocal microscopy explore targeting several green alga Chlamydomonas. These include...
Human tumors display considerable diversity in their genetic makeup but share common physiologic attributes such as a hypoxic microenvironment that contribute to the malignant phenotype. Hypoxic cells switch from eukaryotic initiation factor 4E (eIF4E) eIF4E2 cap-dependent translation synthesize portion of proteins. Here, we show genetically distinct human cancer exploit eIF4E2-directed protein synthesis form cellular masses larger than approximately 0.15 mm, diffusion limit oxygen. Cancer...
Eukaryotic cells under stress repress translation and localize these messenger RNAs (mRNAs) to cytoplasmic RNA granules. We show that specific stimuli induce the assembly of granules in an organelle with bacterial ancestry, chloroplast Chlamydomonas reinhardtii. These (cpSGs) form during oxidative disassemble recovery from stress. Like mammalian granules, cpSGs contain poly(A)-binding protein small, but not large, ribosomal subunit. In addition, mRNAs are continuous flux between polysomes...
Significance DNA methyltransferase 3a (DNMT3a) mediates the de novo methylation of to regulate gene expression and maintain cellular homeostasis. Mutations in DNMT3a primary tumors suggest that epigenetic program is modified during early tumorigenesis. We show a major consequence defects deregulation unscheduled activation EPAS1 (hypoxia-inducible factor 2α) facilitates growth viability under conditions low oxygen availability. This represents critical step tumorigenesis, because cancer...
Ribosomes were once considered static in their composition because of essential role protein synthesis and kingdom-wide conservation. The existence tolerated mutations select ribosomal proteins (RPs), such as Diamond-Blackfan anemia, is evidence that not all ribosome components are essential. Heterogeneity the eukaryotic ribosomes an emerging concept with different pools exist transcript-specificity. Here, we show polysome association altered by low oxygen (hypoxia), a feature tumor...
The oxidation of biological molecules by reactive oxygen species can render them inactive or toxic. This includes the RNA, which appears to underlie detrimental effects oxidative stress, aging, and certain neurodegenerative diseases. Here we investigate management oxidized RNA in chloroplast green alga Chlamydomonas reinhardtii. Our results immunofluorescence microscopy reveal (with 8-hydroxyguanine) localized pyrenoid, a microcompartment where CO2 is assimilated Calvin cycle enzyme Rubisco....
Abstract Background Neuropeptide Y (NPY) is an abundant neurohormone in human breast carcinomas that acts on a class of G-protein coupled receptors, which NPY1R and NPY5R are the most highly expressed. This abundance exploited for cancer imaging, but there interest pharmacological inhibition NPYRs to interrogate their functional relevance cancer. We previously reported mRNA increased by hypoxia inducible factors, sensitizes these receptors NPY stimulation leading enhanced migration...
Translation initiation is a focal point of translational control and requires the binding eIF4E to 5′ cap mRNA. Under conditions extreme oxygen depletion (hypoxia), human cells repress switch an alternative cap-dependent translation mediated by homolog eIF4E, eIF4E2. This forms complex with oxygen-regulated hypoxia-inducible factor 2α can escape repression. mediates under cell culture 1% (to mimic tumor microenvironments), whereas at 21% (ambient air). However, emerging evidence suggests...
Multicellular organisms balance oxygen delivery and toxicity by having pass through several barriers before cellular delivery. In human cell culture, these physiologic are removed, exposing cells to higher levels. Human cultured in ambient air may appear normal, but this is difficult assess without a comparison at oxygen. Here, we examined the effects of culturing throughout spectrum availability on oxidative damage macromolecules, viability, proliferation, antioxidant DNA responses,...
Tumor cell invasion involves targeted localization of proteins required for interactions with the extracellular matrix and proteolysis. The many during these cell–extracellular relies on membrane trafficking mediated in part by SNAREs. SNARE protein syntaxin4 (Stx4) is involved formation invasive structures called invadopodia; however, it unclear how Stx4 function regulated tumor invasion. Munc18c known to regulate activity, here we show that Stx4-mediated invadopodium Biochemical...
Neuropeptide Y (NPY) is an abundant neurohormone in the central and peripheral nervous system involved feeding behavior, energy balance, nociception, anxiety. Several NPY receptor (NPYR) subtypes display elevated expression many cancers including breast tumors where it exploited for imaging diagnosis. Here, we address how hypoxia, a common feature of tumor microenvironment, influences NPYRs. We show that NPY1R NPY5R mRNA abundance induced by hypoxia inducible factor (HIF)-dependent manner...
Hypoxia is a deficiency in oxygen delivery to tissues and connected physiological pathophysiological processes such as embryonic development cancer. The master regulators of homeostasis mammalian cells are the heterodimeric hypoxia-inducible transcription factors 1 2 (HIF-1 HIF-2, respectively). oxygen-labile HIF-2α subunit has been implicated not only but also regulator eukaryotic initiation factor 4E2 (eIF4E2)-directed hypoxic translation. Here, we have identified DEAD box protein family...
Cells remodel splicing and translation machineries to mount specialized gene expression responses stress. Here, we show that hypoxic human cells in 2D 3D culture models increase the relative abundance of a longer mRNA variant ribosomal protein S24 (RPS24L) compared shorter (RPS24S) by favoring inclusion 22 bp cassette exon. Mechanistically, RPS24L RPS24S are induced repressed, respectively, distinct pathways hypoxia: is an autophagy‐dependent manner, while reduced mTORC1 repression...
Abstract Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast NANOG , SNAIL NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), translation subset these stimulated under hypoxia. This leads to accumulation corresponding proteins which induce plasticity “fate-switching” toward stem-cell like phenotypes....
Translational control is a focal point of gene regulation, especially during periods cellular stress. Cap-dependent translation via the eIF4F complex by far most common pathway to initiate protein synthesis in eukaryotic cells, but stress-specific variations this are now emerging. Purifying cap-binding proteins with an affinity resin composed Agarose-linked m7GTP (a 5' mRNA cap analog) useful tool identify factors involved regulation initiation. Hypoxia (low oxygen) stress encountered fetal...