A5086029201- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Cellular Mechanics and Interactions
- Connexins and lens biology
- Genomics and Chromatin Dynamics
- melanin and skin pigmentation
- Wnt/β-catenin signaling in development and cancer
- Wound Healing and Treatments
- Skin and Cellular Biology Research
- Microtubule and mitosis dynamics
- Adenosine and Purinergic Signaling
- Hair Growth and Disorders
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Skin Protection and Aging
- Synthesis and Reactivity of Heterocycles
- Dermatologic Treatments and Research
- Hedgehog Signaling Pathway Studies
- Synthesis of heterocyclic compounds
- Silk-based biomaterials and applications
- Nonmelanoma Skin Cancer Studies
- Virus-based gene therapy research
- Heat shock proteins research
- RNA regulation and disease
Children’s Health Research Institute
2014-2025
Western University
2016-2025
Lawson Health Research Institute
2014-2025
London Health Sciences Centre
2025
Ottawa Hospital
1998-1999
University of Ottawa
1999
University of Alberta
1987-1998
University of Toronto
1997
Hospital for Sick Children
1997
SickKids Foundation
1997
In contrast to skeletal muscle, the mechanisms responsible for activation and maintenance of tissue-specific transcription in cardiac muscle remain poorly understood. A family hormone-encoding genes is expressed a highly specific manner but not myocytes. This includes A- B-type natriuretic peptide (ANP BNP) genes, which encode hormones with crucial roles regulation blood volume pressure. Since these are markers cells, we have used them probe muscle-specific transcription. Cloning functional...
Geoffrey J. Lindeman, Lina Dagnino, Stefan Gaubatz, Yuhui Xu, Roderick T. Bronson, Henry B. Warren, and David M. Livingston The Dana-Farber Cancer Institute/Harvard Medical School, Boston, Massachusetts 02115 USA; Ottawa General Hospital Research Institute, Ottawa, Ontario K1H 8L6 Canada; Tufts University School of Veterinary Medicine, 02111 Center for Animal Resources Comparative Medicine/Harvard USA
We have compared the expression of atrial natriuretic peptide (ANP) and brain (BNP) genes in various human tissues using a quantitative polymerase chain reaction technique. Tissues three subjects, obtained at autopsy, were analyzed. BNP transcripts could be detected central nervous system, lung, thyroid, adrenal, kidney, spleen, small intestine, ovary, uterus, striated muscle. ANP also demonstrated extracardiac including several endocrine organs. In all peripheral tissues, level both was...
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,...
Cardiac myocytes secrete a family of natriuretic and diuretic peptides, including atrial factor (ANF) brain peptide or the rat hormone isoANF. These peptides share structural functional similarities, but their respective physiological roles have yet to be elucidated. Differential expression genes may reflect distinct pathophysiological functions for these peptides. To test this hypothesis, we determined sites ANF isoANF in tissues using polymerase chain reaction amplification transcripts....
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...
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...
Arrestins and integrin-linked kinase (ILK) are important scaffold proteins that regulate myriad cell functions in metazoans. β-arrestins, first identified as critical components G-protein-coupled receptor (GPCR) signaling pathways, participate inflammatory, immunomodulatory tissue repair processes GPCR-dependent -independent manners. ILK is a central mediator of cascades elicited by activation integrins, regulating motility, proliferation, mechanotransduction. In the epidermis, essential for...
In contrast to skeletal muscle, the mechanisms responsible for activation and maintenance of tissue-specific transcription in cardiac muscle remain poorly understood. A family hormone-encoding genes is expressed a highly specific manner but not myocytes. This includes A- B-type natriuretic peptide (ANP BNP) genes, which encode hormones with crucial roles regulation blood volume pressure. Since these are markers cells, we have used them probe muscle-specific transcription. Cloning functional...
The epidermis consists of a squamous epithelium continuously replenished by committed stem cells, which can either self-renew or differentiate. We demonstrated previously that E2F genes are differentially expressed in developing (Dagnino, L., Fry, C. J., Bartley, S. M., Farnham, P., Gallie, B. and Phillips, R. A. (1997) Cell Growth Differ. 8, 553-563). Thus, we hypothesized various proteins likely play distinct growth regulatory roles the undifferentiated cells terminally differentiated...
Integrin-linked kinase (ILK) is key for cell survival, migration, and adhesion, but little known about its role in epidermal development homeostasis vivo. We generated mice with conditional inactivation of the Ilk gene squamous epithelia. These die perinatally exhibit skin blistering severe defects hair follicle morphogenesis, including greatly reduced numbers, failure to progress beyond very early developmental stages, pronounced follicular keratinocyte proliferation. ILK-deficient...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and calcium channel antagonist activity of dialkyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylatesLina Dagnino, Moy Cheong Li-Kwong-Ken, Michael W. Wolowyk, Hla Wynn, Christopher R. Triggle, Edward E. KnausCite this: J. Med. Chem. 1986, 29, 12, 2524–2529Publication Date (Print):December 1, 1986Publication History Published online1 May 2002Published inissue 1 December...
Staphylococcus aureus is a major component of the skin microbiota and causes large number serious infections. S. first interacts with epidermal keratinocytes to breach barrier through mechanisms not fully understood. By use primary from mice epidermis-restricted Ilk gene inactivation control integrin-linked kinase (ILK)-expressing litter-mates, we investigated role ILK in invasion. Heat-killed, but live, bacteria were internalized Rab5- Rab7-positive phagosomes, incubation keratinocyte...
E2F factors are involved in proliferation and apoptosis. To understand the role of E2F-1 epidermis, we screened wild type E2F-1<sup>−/−</sup> keratinocyte mRNA for genes differentially expressed two cell populations. We demonstrate reduced expression integrins α<sub>5</sub>, α<sub>6</sub>, β<sub>1</sub>, β<sub>4</sub> keratinocytes associated with activation Jun terminal kinase Erk upon integrin stimulation. As a consequence altered function, also show impaired migration, adhesion to...
The cardiac natriuretic peptide family includes atrial factor and brain or B-type peptide, also known as iso-atrial (isoANF). Although these peptides contribute to cardiovascular homeostasis, their respective roles remain unclear. To study regulation of isoANF gene expression during progression hypertension, we developed a quantitative polymerase chain reaction protocol measure transcript level in spontaneously hypertensive rat (SHR) hearts. At the onset transcripts 5-week-old SHR were 50%...
The sodium borohydride reduction of 3,5-disubstituted 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)pyridines 2 and 5 in the presence methyl, phenyl, or tert-butyl chloroformate afforded respective 4-(dihydropyridinyl)-1,4-dihydropyridines 4 6 good yield. Products comprised a mixture 1,2- 1,6-dihydropyridinyl regioisomers 4a 4b where was always predominant regioisomer. Compounds possessing 4-[dihydro-1-(phenoxycarbonyl)-3-pyridinyl] substituent, such as 26, were also two 26a 26b, each regioisomer...