A5038513453- Mitochondrial Function and Pathology
- Aquaculture disease management and microbiota
- ATP Synthase and ATPases Research
- Glycosylation and Glycoproteins Research
- Metabolism and Genetic Disorders
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Virus-based gene therapy research
- Parasite Biology and Host Interactions
- Nerve injury and regeneration
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Animal Virus Infections Studies
- Acute Kidney Injury Research
- Adipose Tissue and Metabolism
- Carcinogens and Genotoxicity Assessment
- Advanced biosensing and bioanalysis techniques
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Zebrafish Biomedical Research Applications
- Wnt/β-catenin signaling in development and cancer
- Neurofibromatosis and Schwannoma Cases
- Immune Response and Inflammation
- Genomics and Chromatin Dynamics
University of Calgary
2007-2022
Williams & Associates
2020
William & Mary
2019
Medical University of South Carolina
2011-2018
Friedrich-Loeffler-Institut
2015
The University of Texas MD Anderson Cancer Center
2008-2011
Hartford Hospital
2011
Heritage Medical Research Clinic
2008
University of Miami
2004-2007
University of Alberta
1997-2005
The invasive nature of cancers in general, and malignant gliomas particular, is a major clinical problem rendering tumors incurable by conventional therapies. Using novel glioma mouse model established serial vivo selection, we identified the p75 neurotrophin receptor (p75(NTR)) as critical regulator invasion. Through series functional, biochemical, studies, found that p75(NTR) dramatically enhanced migration invasion genetically distinct frequently exhibited robust expression highly...
Many debilitating conditions are linked to bioenergetic defects. Developing screens probe the genetic and/or chemical basis for such links has proved intractable. Furthermore, there is a need physiologically relevant assay of bioenergetics in whole organisms, especially early stages life where perturbations could increase disease susceptibility with aging. Thus, we asked whether screen and mitochondrial function developing zebrafish embryo. We present multiplexed method embryos from blastula...
Mitochondrial respiratory chain biogenesis is orchestrated by hundreds of assembly factors, many which are yet to be discovered. Using an integrative approach based on clues from evolutionary history, protein localization and human genetics, we have identified a conserved mitochondrial protein, C1orf31/COA6, shown its requirement for complex IV in yeast, zebrafish cells. A recent next-generation sequencing study reported potential pathogenic mutations within the evolutionarily Cx9CxnCx10C...
Abstract Spheroids are three-dimensional cellular models with widespread basic and translational application across academia industry. However, methodological transparency guidelines for spheroid research have not yet been established. The MISpheroID Consortium developed a crowdsourcing knowledgebase that assembles the experimental parameters of 3,058 published spheroid-related experiments. Interrogation this identified heterogeneity in setup spheroids. Empirical evaluation interlaboratory...
The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of kidney. Renal ischemia reperfusion injury (IRI) induces robust monocyte causes acute (AKI). inflammation AKI phenotype were attenuated in Dpep1-/- mice or pretreated with DPEP1 antagonists, including LSALT peptide, nonenzymatic inhibitor. deficiency inhibition...
Significance Inherited pathogenic mutations in genes required for copper delivery to cytochrome c oxidase (CcO) perturb mitochondrial energy metabolism and result fatal disease. A prior attempt treat human patients with these by direct supplementation was not successful, possibly because of inefficient the mitochondria. We performed a targeted search identify compounds that can efficiently transport across biological membranes identified elesclomol (ES), an investigational anticancer drug,...
Opa1 catalyzes fusion of inner mitochondrial membranes and formation the cristae. OPA1 mutations in humans lead to autosomal dominant optic atrophy. knockout mice lose viability around embryonic day 9 from unknown reasons, indicating that is essential for development. Zebrafish are an attractive model studying vertebrate development have been used many years describe developmental events difficult or impractical view mammalian models. In this study, was successfully depleted zebrafish...
Abstract Mitochondria are involved in key cellular functions including energy production, metabolic homeostasis and apoptosis. Normal mitochondrial function is preserved by several interrelated mechanisms. One mechanism – intramitochondrial quality control (IMQC) represented conserved proteases distributed across compartments. Many aspects physiological roles of IMQC components remain unclear. Here, we show that the protease Oma1 required for stability respiratory supercomplexes thus...
The invasive nature of glioblastoma renders them incurable by current therapeutic interventions. Using a novel human glioma model, we previously identified the neurotrophin receptor p75(NTR) (aka CD271) as mediator invasion. Herein, provide evidence that preventing phosphorylation on S303 pharmacological inhibition PKA, or mutational strategy (S303G), cripples p75(NTR)-mediated invasion resulting in serine within C-terminal PDZ-binding motif (SPV) p75(NTR). Consistent with this, deletion...
The MUC1 mucin is normally restricted to the apical surface of breast epithelial cells. In tumors, it frequently overexpressed and underglycosylated. peptide core mediates firm adhesion tumor cells adjacent via binding intercellular molecule-1 (ICAM-1). There increasing evidence that involved in signaling, with current reports focusing on phosphorylation cytoplasmic tail after indirect or artificial modes stimulation. ICAM-1 only known direct ligand extracellular domain. data presented...
The multifunctional signaling protein p75 neurotrophin receptor (p75(NTR)) is a central regulator and major contributor to the highly invasive nature of malignant gliomas. Here, we show that neurotrophin-dependent regulated intramembrane proteolysis (RIP) p75(NTR) required for p75(NTR)-mediated glioma invasion, identify previously unnamed process targeted therapy. Expression cleavage-resistant chimeras or treatment animals bearing p75(NTR)-positive intracranial tumors with clinically...
Abstract MUC1, a transmembrane glycoprotein of the mucin family, when aberrantly expressed on breast cancer cells is correlated with increased lymph node metastases. We have previously shown that MUC1 binds intercellular adhesion molecule-1 (ICAM-1) surrounding accessory and facilitates transendothelial migration MUC1-bearing cells. Nevertheless, underlying molecular mechanism still obscure. In present study, we used novel assay actin cytoskeletal reorganization to show by ligating ICAM-1,...
DNA polymerase gamma (POLG) is essential for replication and repair of mitochondrial (mtDNA). Mutations in POLG cause mtDNA instability a diverse range poorly understood human diseases. Here, we created unique Polg animal model, by modifying polg within the critical highly conserved domain zebrafish. polg+/− offspring were indistinguishable from WT siblings multiple phenotypic biochemical measures. However, polg−/− mutants developed severe depletion one week post-fertilization (wpf), slowly...
Despite extensive molecular characterization, human glioblastoma remains a fatal disease with survival rates measured in months. Little improvement is seen standard surgery, radiotherapy and chemotherapy. Clinical progress hampered by the inability to detect target reservoirs based on diffuse invasive pattern presence of phenotypic heterogeneity. The goal this study was stem-like cells that evade first-line treatments using agents capable delivering imaging enhancers or biotherapeutic cargo....
beta-L-(-)-2',3'-Dideoxy-3'-thiacytidine (3TC) is a cytosine nucleoside analog that potently inhibits the replication of human and duck hepatitis B viruses immunodeficiency virus through activity its 5'-triphosphate ester metabolite. The present study examined intracellular decay 3TC 5'-phosphates tested strategies for modulating cellular content those nucleotides in primary cultures hepatocytes hepatoma 2.2.15 cells CCRF-CEM T lymphoblasts. Inhibition by deoxycytidine 5'-phosphorylation...