11 results on '"Victoria Wong"'
Search Results
2. Rates of event capture of home video EEG
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Ewan S. Nurse, Thilini Perera, Timothy Hannon, Victoria Wong, Kiran M. Fernandes, and Mark J. Cook
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Neurology ,Physiology (medical) ,Neurology (clinical) ,Sensory Systems - Published
- 2023
3. Comparing Bone Shape Models from Deep Learning Processing of MRI to CT-Based Models
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Victoria Wong, Francesco Caliva, Favian Su, Valentina Pedoia, and Drew Lansdown
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Orthopedics and Sports Medicine ,Surgery - Published
- 2023
4. modeling of GM1 gangliosidosis using iPSC-derived cellular and organoid CNS models
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Christopher E. Schmitt, Grace S. Lee, Ouma Onguka, Victoria Wong, Elizabeth Del Greco, Faezeh Sedighi, Charu Reddy, Swetha Santosh, Oluwayomi Akinkugbe, Jacob Artz, Nikki Kruse, Chinping Chng, William C. Hallows, Joseph C. Chen, Hassibullah Akeefe, Adam P. Silverman, and Gjalt Huisman
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Genetics ,Molecular Biology ,Biochemistry - Published
- 2023
5. An engineered β-galactosidase with improved stability and cross-correction for the potential treatment of GM1 Gangliosidosis via AAV gene therapy
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Charu Reddy, Ouma Onguka, Jacob Artz, Christopher Schmitt, Adam Grossman, Swetha Santosh, Oluwayomi Akinkugbe, Victoria Wong, Kahsay Gebretsadik, Faezeh Sedighi, Jinyan Tang, Elizabeth Del Greco, Grace S. Lee, Nikki Kruse, Chinping Chng, Da Duan, William C. Hallows, Joseph C. Chen, Hassibullah Akeefe, Adam P. Silverman, and Gjalt Huisman
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Endocrinology ,Endocrinology, Diabetes and Metabolism ,Genetics ,Molecular Biology ,Biochemistry - Published
- 2023
6. Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells
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Gennady Poda, Marko Jakopović, Levon Halabelian, Methvin Isaac, Nikolina Radulovich, Michael Prakesch, Caroline Huard, Ahmed Aman, Dhananjay Joshi, Zhong Yao, Manuel Chan, Wiebke Schormann, Richard Marcellus, Babu Joseph, Rima Al-awar, Luka Drecun, Mohammed Mohammed, Li Niu, Brigitte L. Thériault, María Sánchez-Osuna, David Uehling, Ahmed Mamai, Ming-Sound Tsao, Jasmin Coulombe-Huntington, Taira Kiyota, Evelyne Lima-Fernandes, Punit Saraon, Ankit Rai, Jamie Snider, David W. Andrews, Cheryl H. Arrowsmith, Farzaneh Aboualizadeh, Natasha B. Leighl, Miroslav Samaržija, Victoria Wong, Anna Lyakisheva, Mike Tyers, Ratheesh Subramanian, Adrian G. Sacher, Fengling Li, Masoud Vedadi, Igor Stagljar, and Shivanthy Pathmanathan
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Mutant ,Coatomer Protein ,Receptor tyrosine kinase ,Structural Biology ,Drug Discovery ,medicine ,Humans ,Epidermal growth factor receptor ,Lung cancer ,Protein Kinase Inhibitors ,Molecular Biology ,Secretory pathway ,coatomer protein complex beta 2 (COPB2) ,epidermal growth factor receptor (EGFR) ,lung cancer ,endoplasmic reticulum stress ,receptor tyrosine kinase ,Gene knockdown ,biology ,Chemistry ,Endoplasmic reticulum ,Receptor Protein-Tyrosine Kinases ,Endoplasmic Reticulum Stress ,medicine.disease ,COPB2 ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,Mutation ,Cancer research ,biology.protein ,Drug Screening Assays, Antitumor ,Protein Processing, Post-Translational ,Signal Transduction - Abstract
Activating mutations in the epidermal growth factor receptor (EGFR) are common driver mutations in non-small cell lung cancer (NSCLC). First, second and third generation EGFR tyrosine kinase inhibitors (TKIs) are effective at inhibiting mutant EGFR NSCLC, however, acquired resistance is a major issue, leading to disease relapse. Here, we characterize a small molecule, EMI66, an analog of a small molecule which we previously identified to inhibit mutant EGFR signalling via a novel mechanism of action. We show that EMI66 attenuates receptor tyrosine kinase (RTK) expression and signalling and alters the electrophoretic mobility of Coatomer Protein Complex Beta 2 (COPB2) protein in mutant EGFR NSCLC cells. Moreover, we demonstrate that EMI66 can alter the subcellular localization of EGFR and COPB2 within the early secretory pathway. Furthermore, we find that COPB2 knockdown reduces the growth of mutant EGFR lung cancer cells, alters the post-translational processing of RTKs, and alters the endoplasmic reticulum (ER) stress response pathway. Lastly, we show that EMI66 treatment also alters the ER stress response pathway and inhibits the growth of mutant EGFR lung cancer cells and organoids. Our results demonstrate that targeting of COPB2 with EMI66 presents a viable approach to attenuate mutant EGFR signalling and growth in NSCLC.
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- 2021
7. A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome
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Annabel Villedieu, Katelyn D. Darowski, Hongbo Guo, Anne-Claude Gingras, Caterina Iorio, Nicole St-Denis, Igor Stagljar, Zhong Yao, Ramy H. Malty, Andrew Emili, Victoria Wong, Benjamin G. Neel, Hiroyuki Aoki, Max Kotlyar, Yang Xu, Shahreen Amin, Igor Jurisica, Fabian Offensperger, and Mohan Babu
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0301 basic medicine ,Phosphatase ,Protein tyrosine phosphatase ,Transfection ,Interactome ,Article ,Receptor tyrosine kinase ,PTPRB ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Two-Hybrid System Techniques ,Protein Interaction Mapping ,Animals ,Humans ,Protein Interaction Maps ,Phosphorylation ,Molecular Biology ,Epidermal Growth Factor ,biology ,Receptor-Like Protein Tyrosine Phosphatases, Class 4 ,Receptor-Like Protein Tyrosine Phosphatases, Class 3 ,Reproducibility of Results ,Cell Biology ,Enzyme Activation ,ErbB Receptors ,HEK293 Cells ,src-Family Kinases ,030104 developmental biology ,Biochemistry ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Signal transduction ,Signal Transduction ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Receptor tyrosine kinases (RTKs) and protein phosphatases comprise protein families that play crucial roles in cell signaling. We used two protein-protein interaction (PPI) approaches, the Membrane Yeast Two-Hybrid (MYTH) and the Mammalian Membrane Two-Hybrid (MaMTH), to map the PPIs between human RTKs and phosphatases. The resulting RTK-phosphatase interactome reveals a considerable number of previously unidentified interactions and suggests specific roles for different phosphatase families. Additionally, the differential PPIs of some protein tyrosine phosphatases (PTPs) and their mutants suggest diverse mechanisms of these PTPs in the regulation of RTK signaling. We further found that PTPRH and PTPRB directly dephosphorylate EGFR and repress its downstream signaling. By contrast, PTPRA plays a dual role in EGFR signaling: besides facilitating EGFR dephosphorylation, it enhances downstream ERK signaling by activating SRC. This comprehensive RTK-phosphatase interactome study provides a broad and deep view of RTK signaling.
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- 2017
8. A Comprehensive Membrane Interactome Mapping of Sho1p Reveals Fps1p as a Novel Key Player in the Regulation of the HOG Pathway in S. cerevisiae
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Alan R. Davidson, Luka Drecun, Rachel R. Miller, Victoria Wong, Monique Rehal, Farzaneh Aboualizadeh, Jamie Snider, Mid Eum Lee, Matthew Jessulat, Meirui Li, Mohan Babu, Mandy H. Y. Lam, Viktor Deineko, Mehrab Ali, Hay-Oak Park, Olivia Wong, Bellal Jubran, and Igor Stagljar
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Glycerol ,Saccharomyces cerevisiae Proteins ,Saccharomyces cerevisiae ,Computational biology ,Interactome ,Article ,SH3 domain ,Protein–protein interaction ,src Homology Domains ,Bimolecular fluorescence complementation ,Structural Biology ,Protein Interaction Mapping ,Immunoprecipitation ,Interactor ,Phosphorylation ,Molecular Biology ,Integral membrane protein ,biology ,Cell Membrane ,Osmolar Concentration ,Membrane Proteins ,biology.organism_classification ,Membrane protein ,Biochemistry ,Mitogen-Activated Protein Kinases ,Signal Transduction - Abstract
Sho1p, an integral membrane protein, plays a vital role in the high-osmolarity glycerol (HOG) mitogen-activated protein kinase pathway in the yeast Saccharomyces cerevisiae. Activated under conditions of high osmotic stress, it interacts with other HOG pathway proteins to mediate cell signaling events, ensuring that yeast cells can adapt and remain viable. In an attempt to further understand how the function of Sho1p is regulated through its protein–protein interactions (PPIs), we identified 49 unique Sho1p PPIs through the use of membrane yeast two-hybrid (MYTH), an assay specifically suited to identify PPIs of full-length integral membrane proteins in their native membrane environment. Secondary validation by literature search, or two complementary PPI assays, confirmed 80% of these interactions, resulting in a high-quality Sho1p interactome. This set of putative PPIs included both previously characterized interactors, along with a large subset of interactors that have not been previously identified as binding to Sho1p. The SH3 domain of Sho1p was found to be important for binding to many of these interactors. One particular novel interactor of interest is the glycerol transporter Fps1p, which was shown to require the SH3 domain of Sho1p for binding via its N-terminal soluble regulatory domain. Furthermore, we found that Fps1p is involved in the positive regulation of Sho1p function and plays a role in the phosphorylation of the downstream kinase Hog1p. This study represents the largest membrane interactome analysis of Sho1p to date and complements past studies on the HOG pathway by increasing our understanding of Sho1p regulation.
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- 2015
9. Preferential enlargement of leukemia cells using cytoskeletal-directed agents and cell cycle growth control parameters to induce sensitivity to low frequency ultrasound
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Matthew Trendowski, Victoria Wong, Thomas P. Fondy, Lauren Gadeberg, Joseph N. Zoino, Michelle Sansky, and Timothy D. Christen
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Pathology ,medicine.medical_specialty ,Cancer Research ,Paclitaxel ,Cytochalasin B ,Ultrasonic Therapy ,Antineoplastic Agents ,Cell Growth Processes ,Biology ,Microtubules ,Culture Media, Serum-Free ,chemistry.chemical_compound ,Mice ,Cell-cycle synchronization ,Depsipeptides ,Ultrasound ,medicine ,Animals ,Humans ,Chemotherapy ,Cell synchronization ,Leukemia L1210 ,Cytoskeleton ,Ultrasonography ,Cytoskeletal-directed agents ,Leukemia ,Cell Death ,Cell growth ,Sonodynamic therapy ,Cell Cycle ,U937 Cells ,medicine.disease ,Cell biology ,chemistry ,Oncology ,Vincristine ,Monocytic leukemia ,Neoplastic cell ,Stem cell - Abstract
Sonodynamic therapy (SDT) is a form of ultrasound therapy that has been shown to preferentially damage malignant cells based on the relatively enlarged size and altered cytology of neoplastic cells in comparison to normal cells. This study sought to determine whether cytoskeletal-directed agents that either disrupt (cytochalasin B and vincristine) or rigidify (jasplakinolide and paclitaxel) microfilaments and microtubules, respectively, affect ultrasonic sensitivity. U937 human monocytic leukemia cell populations were treated with each cytoskeletal-directed agent alone, and then sonicated at 23.5 kHz under relatively low power and intensity (20–40 W; 10–20 W/cm 2 ), or at 20 kHz using moderate power and intensity (60 W; 80 W/cm 2 ). In addition, human leukemia lines U937, THP1, K562, and Molt-4, and the murine leukemia line L1210 were sonicated using pulsed 20 kHz ultrasound (80.6 W; 107.5 W/cm 2 ) both with and without the addition of cytoskeletal-directed agents to assess whether cytoskeletal-directed agents can potentiate ultrasonic sensitivity in different leukemia lines. Human hematopoietic stem cells (hHSCs) and leukocytes were sonicated with continuous 23.5 kHz ultrasound (20 W; 10 W/cm 2 ) to determine whether this approach elicited the preferential damage of neoplastic cells over normal blood components. To determine whether ultrasonic sensitivity is exclusively dependent on cell size, leukemia cells were also enlarged via alteration of cell growth parameters including serum deprivation and re-addition, and plateau-phase subculturing. Results indicated that cytochalasin B/ultrasound treatments had the highest rates of initial U937 cell damage. The cells enlarged and partially synchronized, either by serum deprivation and re-addition or by plateau-phase subculturing and synchronous release, were not comparably sensitive to ultrasonic destruction based solely on their cell size. In addition, cytochalasin B significantly potentiated the ultrasonic sensitivity of all neoplastic cell lines, but not in normal blood cells, suggesting that preferential damage is attainable with this treatment protocol. Therefore, it is likely that ultrasonic cell lysis depends not only on cell size and type, but also on the specific molecular mechanisms used to induce cell enlargement and their effects on cell integrity. This is supported by the fact that either the microfilament-or microtubule-disrupting agent produced a higher rate of lysis for cells of a given size than the corresponding stabilizing agents.
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- 2015
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10. CHIP-MYTH: A novel interactive proteomics method for the assessment of agonist-dependent interactions of the human β2-adrenergic receptor
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Julia Petschnigg, Jeffrey L. Wrana, Corey Nislow, Igor Stagljar, Max Kotlyar, Saranya Kittanakom, Anthony Arnoldo, Lawrence E. Heisler, Igor Jurisica, Victoria Wong, and Miriam Barrios-Rodiles
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Biophysics ,Cell Biology ,Computational biology ,Biology ,Proteomics ,Biochemistry ,Interactome ,Protein–protein interaction ,Drug development ,Heterotrimeric G protein ,Signal transduction ,Molecular Biology ,Integral membrane protein ,G protein-coupled receptor - Abstract
G-protein coupled receptors (GPCRs) are involved in a variety of disease processes and comprise major drug targets. However, the complexity of integral membrane proteins such as GPCRs makes the identification of their interacting partners and subsequent drug development challenging. A comprehensive understanding of GPCR protein interaction networks is needed to design effective therapeutic strategies to inhibit these drug targets. Here, we developed a novel split-ubiquitin membrane yeast two-hybrid (MYTH) technology called CHIP-MYTH, which allows the unbiased characterization of interaction partners of full-length GPCRs in a drug-dependent manner. This was achieved by coupling DNA microarray technology to the MYTH approach, which allows a quantitative evaluation of interacting partners of a given integral membrane protein in the presence or absence of drug. As a proof of principle, we applied the CHIP-MYTH approach to the human β2-adrenergic receptor (β2AR), a target of interest in the treatment of asthma, chronic obstructive pulmonary disease (COPD), neurological disease, cardiovascular disease, and obesity. A CHIP-MYTH screen was performed in the presence or absence of salmeterol, a long-acting β2AR-agonist. Our results suggest that β2AR activation with salmeterol can induce the dissociation of heterotrimeric G-proteins, Gαβγ, into Gα and Gβγ subunits, which in turn activates downstream signaling cascades. Using CHIP-MYTH, we confirmed previously known and identified novel β2AR interactors involved in GPCR-mediated signaling cascades. Several of these interactions were confirmed in mammalian cells using LUminescence-based Mammalian IntERactome (LUMIER) and co-immunoprecipitation assays. In summary, the CHIP-MYTH approach is ideal for conducting comprehensive protein-protein interactions (PPI) screenings of full-length GPCRs in the presence or absence of drugs, thus providing a valuable tool to further our understanding of GPCR-mediated signaling.
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- 2014
11. Monitoring Protein-Protein Interactions between the Mammalian Integral Membrane Transporters and PDZ-interacting Partners Using a Modified Split-ubiquitin Membrane Yeast Two-hybrid System
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Mia Bertic, Randy A. Hall, Serge M. Gisler, Tamara Radanovic, Daniel Guido Fuster, Orson W. Moe, Saranya Kittanakom, Jürg Biber, Heini Murer, Igor Stagljar, Victoria Wong, Daniel Markovich, University of Zurich, and Stagljar, I
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1303 Biochemistry ,Xenopus ,Two-hybrid screening ,PDZ domain ,PDZ Domains ,610 Medicine & health ,Saccharomyces cerevisiae ,Models, Biological ,Biochemistry ,10052 Institute of Physiology ,Analytical Chemistry ,Protein–protein interaction ,Mice ,Two-Hybrid System Techniques ,1312 Molecular Biology ,Animals ,Humans ,Cloning, Molecular ,Lipid bilayer ,Molecular Biology ,Integral membrane protein ,Cells, Cultured ,Mammals ,1602 Analytical Chemistry ,biology ,Ubiquitin ,Membrane transport protein ,Research ,Peripheral membrane protein ,Membrane Proteins ,Membrane Transport Proteins ,Rats ,Cell biology ,Membrane protein ,10076 Center for Integrative Human Physiology ,Oocytes ,biology.protein ,570 Life sciences ,Female ,Plasmids ,Protein Binding - Abstract
PDZ-binding motifs are found in the C-terminal tails of numerous integral membrane proteins where they mediate specific protein-protein interactions by binding to PDZ-containing proteins. Conventional yeast two-hybrid screens have been used to probe protein-protein interactions of these soluble C termini. However, to date no in vivo technology has been available to study interactions between the full-length integral membrane proteins and their cognate PDZ-interacting partners. We previously developed a split-ubiquitin membrane yeast two-hybrid (MYTH) system to test interactions between such integral membrane proteins by using a transcriptional output based on cleavage of a transcription factor from the C terminus of membrane-inserted baits. Here we modified MYTH to permit detection of C-terminal PDZ domain interactions by redirecting the transcription factor moiety from the C to the N terminus of a given integral membrane protein thus liberating their native C termini. We successfully applied this “MYTH 2.0” system to five different mammalian full-length renal transporters and identified novel PDZ domain-containing partners of the phosphate (NaPi-IIa) and sulfate (NaS1) transporters that would have otherwise not been detectable. Furthermore this assay was applied to locate the PDZ-binding domain on the NaS1 protein. We showed that the PDZ-binding domain for PDZK1 on NaS1 is upstream of its C terminus, whereas the two interacting proteins, NHERF-1 and NHERF-2, bind at a location closer to the N terminus of NaS1. Moreover NHERF-1 and NHERF-2 increased functional sulfate uptake in Xenopus oocytes when co-expressed with NaS1. Finally we used MYTH 2.0 to demonstrate that the NaPi-IIa transporter homodimerizes via protein-protein interactions within the lipid bilayer. In summary, our study establishes the MYTH 2.0 system as a novel tool for interactive proteomics studies of membrane protein complexes.
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- 2008
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