A5011542293- Connexins and lens biology
- Heat shock proteins research
- Thermoregulation and physiological responses
- Ultrasound and Hyperthermia Applications
- Adipose Tissue and Metabolism
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Nicotinic Acetylcholine Receptors Study
- Wnt/β-catenin signaling in development and cancer
- RNA regulation and disease
- Bacterial Genetics and Biotechnology
- Cancer-related molecular mechanisms research
- Cardiovascular Disease and Adiposity
- Photoacoustic and Ultrasonic Imaging
- Epigenetics and DNA Methylation
- Skin Protection and Aging
- RNA Research and Splicing
- Ultrasound Imaging and Elastography
- Hippo pathway signaling and YAP/TAZ
- Biochemical effects in animals
- Electrospun Nanofibers in Biomedical Applications
- RNA modifications and cancer
- Tissue Engineering and Regenerative Medicine
- Acute Myeloid Leukemia Research
- Dermatologic Treatments and Research
Western University
2006-2025
Daemen College
2024
Stem Cell Network
2022
Epizyme (United States)
2011-2019
Stanford University
2012-2015
Duquesne University
2003-2006
Robarts Clinical Trials
2005-2006
Saint Vincent College
2002
A survey of the human genome was performed to understand constituency protein methyltransferases (both arginine and lysine methyltransferases) relatedness their catalytic domains. We identified 51 methyltransferase proteins based on similarity canonical Drosophila Su(var)3-9, enhancer zeste (E(z)), trithorax (trx) domain. Disruptor telomeric silencing-1-like, a known methyltransferase, did not fit within family, but group with methyltransferases, along 44 other proteins, including METTL...
EPZ-5676 [(2<i>R</i>,3<i>R</i>,4<i>S</i>,5<i>R</i>)-2-(6-amino-9<i>H</i>-purin-9-yl)-5-((((1<i>r</i>,3<i>S</i>)-3-(2-(5-(<i>tert</i>-butyl)-1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol], a small-molecule inhibitor of the protein methyltransferase DOT1L, is currently under clinical investigation for acute leukemias bearing <i>MLL</i>-rearrangements (<i>MLL</i>-r). In this study, we evaluated in combination with standard care (SOC)...
Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow passage of ions and molecules up to kDa, ATP other metabolites. In this study, we show that highly human melanoma tumors at all stages disease progression, as well patient-derived cells established cell lines. Reducing protein levels using shRNA or inhibiting channel function with blockers, carbenoxolone (CBX) probenecid (PBN), significantly decreased growth migration,...
In this study, we explored the intricate relationship between Pannexin 1 (PANX1) and Hippo signaling pathway effector, Yes‐associated protein (YAP). Analysis of The Cancer Genome Atlas (TCGA) data revealed a significant positive correlation PANX1 mRNA core components, [YAP], Transcriptional coactivator with PDZ‐binding motif [TAZ], scaffold, Ras GTPase‐activating‐like IQGAP1 [IQGAP1], in invasive cutaneous melanoma breast carcinoma. Furthermore, demonstrated that expression is upregulated...
Melanoma is the most aggressive skin malignancy with increasing incidence worldwide. Pannexin1 (PANX1), a member of pannexin family channel-forming glycoproteins, regulates cellular processes in melanoma cells including proliferation, migration, and invasion/metastasis. However, mechanisms responsible for coordinating regulating PANX1 function remain unclear. Here, we demonstrated direct interaction between C-terminal region N-terminal portion β-catenin, key transcription factor Wnt pathway....
Immunotherapies for malignant melanoma seek to boost the anti‐tumoral response of CD8 + T cells, but have a limited patient rate, in part due tumoral immune cell infiltration. Genetic or pharmacological inhibition pannexin 1 (PANX1) channel‐forming protein is known decrease tumorigenic properties vitro and ex vivo . Here, we crossed Panx1 knockout ( −/− ) mice with inducible model Braf CA , Pten loxP Tyr::CreER T2 (BPC). We found that deleting gene does not reduce BRAF(V600E)/Pten‐driven...
Here we characterize seven Cx30.3 gene variants (R22H, S26Y, P61R, C86S, E99K, T130M and M190L) clinically associated with the rare skin disorder erythrokeratodermia variabilis et progressiva (EKVP) in tissue-relevant differentiation-competent rat epidermal keratinocytes (REKs). We found that all variants, when expressed alone or together wildtype (WT) Cx30.3, had capacity to traffic form gap junctions an efficiency like WT Cx30.3. was have a slower relative turnover than Cx43. However, more...
Abstract Background The regulation and function of mammalian RNAs has been increasingly appreciated to operate via RNA-protein interactions. With the recent discovery thousands novel human RNA molecules by high-throughput sequencing, efficient methods uncover interactions are urgently required. Existing study proteins associated with a given laborious require substantial amounts cell-derived starting material. To overcome these limitations, we have developed rapid large-scale approach...
Pannexin 1 (Panx1) is a channel-forming glycoprotein important in paracrine signaling and cellular development. In this study, we discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass reduced lean compared to wild type (WT) under normal diet. Despite having higher content, KO on high diet exhibited no differences weight gain blood markers of obesity as WT controls, except for an increase glucose insulin levels. However, metabolic cage data revealed these...
Pannexin 1 (PANX1) is a glycoprotein that forms large pore channels capable of passing ions and metabolites such as ATP for cellular communication. PANX1 has been implicated in many diseases including breast cancer melanoma, where inhibition or deletion reduced the tumorigenic metastatic properties cells. We interrogated effect single amino acid changes various domains using naturally occurring variants reported patient tumors. found previously variant (Q5H) present cells, but was not...
Epidermal keratinocytes are enriched with at least nine connexins that key regulators of epidermal homeostasis. The role Cx30.3 in and health became evident when fourteen autosomal dominant mutations the Cx30.3-encoding GJB4 gene were linked to a rare incurable skin disorder called erythrokeratodermia variabilis et progressiva (EKVP). While these variants EKVP, they remain largely uncharacterized hindering therapeutic options. In this study, we characterize expression functional status three...
ABSTRACT Connexins are channel-forming proteins that function to facilitate gap junctional intercellular communication. Here, we use dual cell voltage clamp and dye transfer studies corroborate past findings showing Cx31.1 (encoded by GJB5) is defective in junction channel formation, illustrating alone does not form functional channels connexin-deficient mammalian cells. Rather transiently localizes the secretory pathway with a subpopulation reaching surface, which rarely seen puncta...
Abstract Pannexin (PANX) channels are present in skin and facilitate the movement of signalling molecules during cellular communication. PANX1 PANX3 function homeostasis keratinocyte differentiation but were previously reduced a small cohort human cutaneous squamous cell carcinoma (cSCC) tumours compared to normal epidermis. In our study, we used SCC-13 cells, limited publicly available RNA-seq data larger cSCC patient-matched samples analyze expression determine association between their...
Abstract Pannexin (PANX) channels are present in skin and facilitate the movement of signalling molecules during cellular communication. PANX1 PANX3 function homeostasis keratinocyte differentiation but were previously reduced a small cohort human cutaneous squamous cell carcinoma (cSCC) tumours compared to normal epidermis. In our study we used SCC‐13 cells, limited publicly available RNA‐seq data larger cSCC patient‐matched samples analyse expression determine association between their...
Pannexins (Panx1, 2, 3) are channel-forming glycoproteins expressed in mammalian tissues. We previously reported that N-glycosylation acts as a regulator of the localization and intermixing Panx1 Panx3, but its effects on Panx2 currently unknown. can regulate channel properties, both pannexins have been implicated neuronal cell death after ischemia. Our objectives were to validate predicted site study glycosylation capacity interact with Panx1. used site-directed mutagenesis, enzymatic...
Melanoma is one of the most aggressive types tumors and exhibits high metastatic potential. Fes-related (FER) kinase a non-receptor tyrosine that has been implicated in growth metastasis various epithelial tumors. In this study, we have examined role FER plays melanoma at molecular level. FER-depleted cells exhibit impaired Wnt/β-catenin pathway activity, as well multiple proteomic changes, which include decreased abundance L1-cell adhesion molecule (L1-CAM). Consistent with pro-metastatic...
Abstract Small intestinal submucosa (SIS) is a naturally occurring, acellular biomaterial that has been used extensively as soft tissue replacement, scaffold for engineering, and substrate the study of cells in 3D culture. The aim this to define culture parameters promote neotissue formation with use dermal fibroblasts SIS. SIS sheets were seeded cultured 4 weeks. resultant cell‐scaffold composites (CSCs) media alone, supplemented ascorbic acid, or fibronectin‐pretreated acid. CSCs analyzed...
The CspE protein from Escherichia coli K12 is a single-stranded nucleic acid-binding that plays role in chromosome condensation vivo. We report here binds to DNA containing 6 or more contiguous dT residues with high affinity (KD < 30 nm). interactions are predominantly through base-specific contacts. When an oligonucleotide contains fewer than residues, the primarily electrostatic. minimal length of which salt-resistant manner eight nucleotides. also show exists as dimer solution. present...