A5068892924- Connexins and lens biology
- Cancer-related molecular mechanisms research
- Heat shock proteins research
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Congenital Diaphragmatic Hernia Studies
- RNA modifications and cancer
- Congenital Anomalies and Fetal Surgery
- Esophageal and GI Pathology
- Sarcoma Diagnosis and Treatment
- Virus-based gene therapy research
- Muscle Physiology and Disorders
- Neuroblastoma Research and Treatments
- Pulmonary Hypertension Research and Treatments
- Yersinia bacterium, plague, ectoparasites research
- Wnt/β-catenin signaling in development and cancer
- Erythrocyte Function and Pathophysiology
- Spaceflight effects on biology
- Cell death mechanisms and regulation
- Ion channel regulation and function
- Ion Channels and Receptors
- Nicotinic Acetylcholine Receptors Study
- Metastasis and carcinoma case studies
- Genetic and Kidney Cyst Diseases
- Surgical site infection prevention
Children's Hospital of Eastern Ontario
2012-2024
University of Ottawa
2013-2024
Western University
2006-2010
University of British Columbia
2010
Children's Hospital of Western Ontario
2009
Institute of Cell Biology and Neurobiology
2007
Victoria Hospital
2006
University of Toronto
1999-2005
Hospital for Sick Children
1999-2005
SickKids Foundation
2000-2005
Pannexins are mammalian orthologs of the invertebrate gap junction proteins innexins and thus have been proposed to play a role in junctional intercellular communication. Localization exogenously expressed pannexin 1 (Panx1) 3 (Panx3), together with pharmacological studies, revealed cell surface distribution profile life cycle dynamics that were distinct from connexin 43 (Cx43, encoded by Gja1). Furthermore, N-glycosidase treatment showed both Panx1 (∼41-48 kD species) Panx3 (∼43 kD)...
Increased expression of the glycoprotein tenascin-C (TN) is associated with progression clinical and experimental pulmonary hypertension. In cultured smooth muscle cells (SMCs) TN induced by matrix metalloproteinases (MMPs) amplifies proliferative response to growth factors. Conversely, suppression leads SMC apoptosis. We now report that hypertrophied rat arteries in organ culture, which progressively thicken association cell proliferation accumulation, can be made regress inhibiting either...
Connexin43 (Cx43) has been reported to interact with caveolin (Cav)-1, but the role of this association and whether other members family bind Cx43 had yet be established. In study, we show that coimmunoprecipitates colocalizes Cav-1 Cav-2 in rat epidermal keratinocytes. The colocalization was confirmed keratinocytes from human epidermis vivo. Our mutation Far Western analyses revealed C-terminal tail is required for its Cavs Cx43/Cav-1 interaction direct. results indicate newly synthesized...
Pannexin (Panx) 1 and Panx3 are integral membrane proteins that share some sequence homology with the innexin family of invertebrate gap junctions. They expressed in mammalian skin. Pannexins have been reported to form functional mechanosensitive single-membrane channels, but their importance regulating cellular function is poorly understood. In this study, Panx1 were detected epidermis 13.5 day embryonic mice. Compared newborn mice, there was less expression both thin thick murine skin,...
Abstract —Increased elastase activity and deposition of the matrix glycoprotein tenascin-C (TN), codistributing with proliferating smooth muscle cells (SMCs), are features pulmonary vascular disease. In artery (PA) SMC cultures, TN is regulated by metalloproteinases (MMPs) mechanical stress. On attached collagen gels, MMPs upregulate TN, leading to proliferation, whereas on floating collagen, reduced suppress induce apoptosis. We now investigate response SMCs in whole vessel comparing...
Connexin43 (Cx43) is known to have tumor-suppressive effects, but the underlying mechanisms are still poorly understood. In keratinocytes, we previously showed that COOH-terminal domain of Cx43 directly interacts with tumor suppressor Cav-1. We now show rat epidermal keratinocytes (REK) reduced in present features epithelial-to-mesenchymal transition and more invasive than their control counterparts, whereas overexpression inhibited 12-O-tetradecanoyl-phorbol-13-acetate (TPA)- growth factor...
Having shown that Panx1 and Panx3 are expressed in the epidermis, we investigated their distribution human skin adnexal structures cancer. Both proteins were found hair follicles, sebaceous eccrine glands, as well blood vessels. was detected punctate or diffuse intracellular labeling, while only observed staining, suggesting different functions. We also identified immunoreactive ∼70 kD species modulated during keratinocyte differentiation Panx3. Since our data indicate pannexins regulated...
Induction of smooth muscle cell apoptosis is critical to the reversal severe structural remodeling in hypertensive pulmonary arteries during disease regression. This process involves coordinated resorption pathologically deposited extracellular matrix, including elastin, and occurs presence serine elastase matrix metalloproteinase inhibitors. Here, we show that apoptotic cells exhibit extensive degradation elastin coincident with surface immunolocalization release caspases. We further...
Residual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. Translational control of mRNA is an important feature immunity, yet the identity translationally regulated mRNAs functioning host defense remains ill-defined. We report translatomes resistant murine "4T1" breast infected three most clinically advanced viruses: herpes simplex virus 1, reovirus, and vaccinia virus. Common among all infections are de-repressed mRNAs, including Inpp5e, encoding...
Abstract Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is an aggressive cancer with a poor prognosis. Despite current management, 5-year survival rate for patients metastatic RMS ∼30%; underscoring need to develop better treatment strategies. We have recently reported that pannexin 1 (PANX1) levels are downregulated and restoring its expression inhibits progression. Here, we surveyed characterized molecular changes induced by PANX1 re-expression RMS. cataloged...
Abstract Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise muscle beds, express key myogenic regulatory factors. However, their developmental program remains blocked proliferative phase with cells unable to exit cell cycle fuse into myotubes. Recently, we uncovered a role for RNA-binding protein Staufen1 during differentiation through regulation of c-myc translation. Given known...
Pannexin 1 (Panx1) and 3 (Panx3) are single membrane channels recently implicated in myogenic commitment, as well myoblast proliferation differentiation vitro. However, their expression patterns during skeletal muscle development regeneration had yet to be investigated. Here, we show that Panx1 levels increase becoming highly expressed together with Panx3 adult muscle. In mice, were differentially fast‐ slow‐twitch muscles. We also report Panx1/PANX1 Panx3/PANX3 co‐expressed mouse human...
Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma of childhood thought to arise from impaired differentiation skeletal muscle progenitors. We have recently identified Pannexin 1 (PANX1) channels as a novel regulator myogenesis. In the present study, we determined that PANX1 transcript and protein levels are down-regulated in embryonal (eRMS) alveolar RMS (aRMS) patient-derived cell lines primary tumor specimens compared differentiated myoblasts tissue, respectively. While not...
Abstract Background Duchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive weakness, damage, and wasting. While the cause of DMD an X-linked loss function mutation in gene encoding dystrophin, exact mechanisms that perpetuate disease progression are unknown. Our laboratory has demonstrated pannexin 1 (Panx1 rodents; PANX1 humans) critical for development, strength, regeneration male skeletal muscle. In normal muscle, Panx1 part a multiprotein complex...
Rhabdomyosarcoma (RMS) is a deadly cancer of skeletal muscle origin. Pannexin 1 (PANX1) down-regulated in RMS and increasing its levels drastically inhibits progression. PANX1 upregulation thus represents prospective new treatment strategy for this malignancy. However, the mechanisms regulating expression, other contexts, remain largely unknown. Here we show that both normal express comparable amount mRNAs, but surprisingly canonical 5' untranslated region (5' UTR) or leader transcript...