- Biotin and Related Studies
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Hippo pathway signaling and YAP/TAZ
- Pluripotent Stem Cells Research
- Click Chemistry and Applications
- Ubiquitin and proteasome pathways
- vaccines and immunoinformatics approaches
- COVID-19 Clinical Research Studies
- Bioinformatics and Genomic Networks
- SARS-CoV-2 detection and testing
- RNA and protein synthesis mechanisms
- Gene expression and cancer classification
- Cellular transport and secretion
- Wnt/β-catenin signaling in development and cancer
- Genomics and Chromatin Dynamics
- Cancer therapeutics and mechanisms
- Advanced Proteomics Techniques and Applications
- bioluminescence and chemiluminescence research
- TGF-β signaling in diseases
- Animal Virus Infections Studies
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Cell Image Analysis Techniques
- Genomics and Phylogenetic Studies
Mount Sinai Hospital
2012-2025
Lunenfeld-Tanenbaum Research Institute
2016-2025
University of Toronto
2007-2023
Sinai Health System
2019-2022
Harvard University
2012
Broad Institute
2012
Canada Research Chairs
2011
The Scarborough Hospital
2007
While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about saliva and its relationship systemic levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA IgM responses spike protein (full length trimer) receptor-binding domain (RBD) serum of acute convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared negative controls. Anti-SARS-CoV-2 were readily...
In most human cancers, only a few genes are mutated at high frequencies; low frequencies. The functional consequences of these recurrent but infrequent "long tail" mutations often unknown. We focused on 484 long tail in head and neck squamous cell carcinoma (HNSCC) used vivo CRISPR to screen for that, upon mutation, trigger tumor development mice. Of the 15 tumor-suppressor identified, ADAM10 AJUBA suppressed HNSCC haploinsufficient manner by promoting NOTCH receptor signaling. or...
Type II DNA topoisomerases (TOP2) regulate topology by generating transient double stranded breaks during replication and transcription. Topoisomerase beta (TOP2B) facilitates rapid gene expression functions at the later stages of development differentiation. To gain new insight into genome biology TOP2B, we used proteomics (BioID), chromatin immunoprecipitation, high-throughput chromosome conformation capture (Hi-C) to identify novel proximal TOP2B protein interactions characterize genomic...
Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to virus within few weeks infection, but duration this and how it correlates clinical outcomes has not been completely characterized. Of particular importance is identification infection that would support public health decision-making on treatment approaches, vaccination strategies, convalescent plasma therapy. While ELISA-based assays detect quantitate antibodies...
Abstract Viral replication is dependent on interactions between viral polypeptides and host proteins. Identifying virus-host protein can thus uncover unique opportunities for interfering with the virus life cycle via novel drug compounds or repurposing. Importantly, many viral-host take place at intracellular membranes poorly soluble organelles, which are difficult to profile using classical biochemical purification approaches. Applying proximity-dependent biotinylation (BioID) fast-acting...
Abstract The world is facing a global pandemic of COVID-19 caused by the SARS-CoV-2 coronavirus. Here we describe collection codon-optimized coding sequences for cloned into Gateway-compatible entry vectors, which enable rapid transfer variety expression and tagging vectors. freely available. We hope that widespread availability this resource will many subsequent molecular studies to better understand viral life cycle how block it.
Summary Key steps of viral replication take place at host cell membranes, but the detection membrane-associated protein-protein interactions using standard affinity-based approaches (e.g. immunoprecipitation coupled with mass spectrometry, IP-MS) is challenging. To learn more about SARS-CoV-2 - protein that we utilized a complementary technique, proximity-dependent biotin labeling (BioID). This approach uncovered virus-host topology network comprising 3566 proximity amongst 1010 proteins,...
Abstract While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about mucosal immune and its relationship systemic levels. Since initially replicates upper airway, oral cavity likely an important parameter that influences course of infection, but how it correlates serum not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA IgM responses spike protein (full length trimer) receptor binding domain (RBD) (n=496)...
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% TNBCs, but little known regarding the genetic drivers associated with this event. Here, we show somatic deletion region syntenic human 5q33.2–35.3 mouse model TNBC. Mechanistically, identify KIBRA as major factor contributing effects on tumor growth metastatic progression. Re-expression impairs metastasis vivo inhibits tumorsphere...
ABSTRACT Compartmentalization is a defining characteristic of eukaryotic cells, partitioning cellular processes into discrete subcellular locations. High throughput microscopy 1 and biochemical fractionation coupled with mass spectrometry 2–6 have helped to define the proteomes variety organelles macromolecular structures. However, many other intracellular compartments remained refractory such approaches, due for example difficulty in purifying non-membrane bound Proximity-dependent...
Abstract Phagocytosis is a complex sequence of events involving coordinated remodeling the plasma membrane with underlying cytoskeleton. Although role actin cytoskeleton becoming increasingly elucidated, microtubules (MTs) remains poorly understood. Here, we examine MTs during FcγR-mediated phagocytosis in RAW264.7 mouse macrophages. We observe that extend into phagosomal cups. The MT-depolymerizing agents, colchicine and nocodazole, cause sizeable reduction large particles cells. primed...
The Crumbs complex is an important determinant of epithelial apical-basal polarity that functions in regulation tight junctions, resistance to epithelial-to-mesenchymal transitions and as a tumour suppressor. Although the functional role being elucidated, its poorly understood. Here, we show suppression RNF146, E3 ubiquitin ligase recognizes ADP-ribosylated substrates, tankyrase, poly(ADP-ribose) polymerase, disrupts junctional disturbs function junctions. We RNF146 binds number...
Proximity-dependent biotinylation strategies have emerged as powerful tools to characterize the subcellular context of proteins in living cells. The popular BioID approach employs an abortive E. coli biotin ligase mutant (R118G; denoted BirA*), which when fused a bait protein eNAbles covalent endogenous proximal polypeptides. This has been mainly applied study proximity immortalized mammalian cell lines. To expand application space BioID, here we describe set lentiviral vectors that eNAble...
Abstract An accurate spatial representation of protein-protein interaction networks is needed to achieve a realistic and biologically relevant interactomes. Here, we leveraged the information included in Proximity-Dependent Biotin Identification (BioID) interactomes SARS-CoV-2 proteins calculate weighted distances model organization SARS-CoV-2-human interactome three dimensions (3D) within cell-like volume. Cell regions with viral occupancy were highlighted, along coordination exploiting...
Article11 August 2015Open Access Source Data Integrative genomics positions MKRN1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network Paul A Cassar Institute of Medical Science, University Toronto, ON, Canada Collaborative Program in Genome Biology and Bioinformatics, Search for more papers by this author Richard L Carpenedo Sprott Centre Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Payman Samavarchi-Tehrani Department Molecular Genetics,...