A5071097577- Bioinformatics and Genomic Networks
- Biotin and Related Studies
- Microbial Natural Products and Biosynthesis
- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Gut microbiota and health
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- RNA Research and Splicing
- Protein Structure and Dynamics
- RNA modifications and cancer
- Lipid metabolism and biosynthesis
- Genomics and Chromatin Dynamics
- Genomics and Phylogenetic Studies
- Cellular transport and secretion
- Cancer-related gene regulation
- Insect Resistance and Genetics
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neuropharmacology Research
- Machine Learning in Bioinformatics
- Artificial Intelligence in Healthcare
- Microbial Metabolic Engineering and Bioproduction
- Protein Degradation and Inhibitors
University of Ottawa
2017-2025
Scripps (United States)
2025
Torrey Pines Institute For Molecular Studies
2025
Scripps Institution of Oceanography
2025
Ottawa Institute of Systems Biology
2021-2024
Scripps Research Institute
2014-2019
McGill University
2008-2017
Bipar
2017
Macrophage autophagy is a highly anti-atherogenic process that promotes the catabolism of cytosolic lipid droplets (LDs) to maintain cellular homeostasis. Selective relies on tags such as ubiquitin and set selectivity factors including selective receptors (SARs) label specific cargo for degradation. Originally described in yeast cells, "lipophagy" refers degradation LDs by autophagy. Yet, how are targeted poorly defined. Here, we employed mass spectrometry identify lipophagy within...
Abstract A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A POLR3B . Here we report eight these carrying recessive POLR1C , a gene encoding shared POLR1 POLR3 subunit, also mutated some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics ChIP sequencing, demonstrate that leukodystrophy-causative mutations,...
Abstract Mutations in proteins like FUS which cause Amyotrophic Lateral Sclerosis (ALS) result the aberrant formation of stress granules while ALS-linked mutations other impede elimination granules. Repeat expansions C9ORF72, major ALS, reduce C9ORF72 levels but how this impacts is uncertain. Here, we demonstrate that associates with autophagy receptor p62 and controls by autophagy. This requires to associate via Tudor protein SMN proteins, including FUS, are symmetrically methylated on...
Methylation is a post-translational modification that can affect numerous features of proteins, notably cellular localization, turnover, activity, and molecular interactions. Recent genome-wide analyses have considerably extended the list human genes encoding putative methyltransferases. Studies on protein methyltransferases revealed regulatory function methylation not limited to epigenetics, with many non-histone substrates now being discovered. We present here our findings novel family...
Palmitoylation involves the reversible posttranslational addition of palmitate to cysteines and promotes membrane binding subcellular localization. Recent advancements in detection identification palmitoylated proteins have led multiple palmitoylation proteomics studies but these datasets are contained within large supplemental tables, making downstream analysis data mining time-consuming difficult. Consequently, we curated from 15 into one compendium containing 1,838 genes encoding...
Abstract Mitochondria share attributes of vesicular transport with their bacterial ancestors given ability to form mitochondrial‐derived vesicles (MDVs). MDVs are involved in mitochondrial quality control and formation is enhanced stress may, therefore, play a potential role mitochondrial‐cellular communication. However, MDV proteomic cargo has remained mostly undefined. In this study, we strategically used an vitro budding/reconstitution assay on cardiac mitochondria, followed by graded...
RNA polymerase II (RNAPII), the 12-subunit enzyme that synthesizes all mRNAs and several non-coding RNAs in eukaryotes, plays a central role cell function. Although multiple proteins are known to regulate activity of RNAPII during transcription, little is about machinery controls fate before or after transcription. We used systematic protein affinity purification coupled mass spectrometry (AP-MS) characterize high resolution network interactions soluble fraction human extracts. Our analysis...
Intact protein analysis via top-down mass spectrometry (MS) provides the unique capability of fully characterizing isoforms and combinatorial post-translational modifications (PTMs) compared to bottom-up MS approach. Front-end separation poses a challenge for analyzing complex mixtures intact proteins on proteomic scale. Here we applied capillary electrophoresis (CE) through sheathless electrophoresis-electrospray ionization (CESI) interface coupled an Orbitrap Elite spectrometer profile...
Amyloid beta (Aβ) peptides impair multiple cellular pathways and play a causative role in Alzheimer's disease (AD) pathology, but how the brain proteome is remodeled by this process unknown. To identify protein networks associated with AD-like we performed global quantitative proteomic analysis three mouse models at young old ages. Our revealed robust increase Apolipoprotein E (ApoE) levels nearly all regions increased Aβ levels. Taken together prior findings on ApoE driving accumulation,...
The majority of large-scale proteomics quantification methods yield long lists quantified proteins that are often difficult to interpret and poorly reproduced. Computational approaches required analyze such intricate quantitative data sets. We propose a statistical approach computationally identify protein sets (e.g., Gene Ontology (GO) terms) significantly enriched with abundant reproducible measurements across set replicates. To this end, we developed PSEA-Quant, enrichment analysis...
Polyphosphates (polyPs) are long chains of inorganic phosphates linked by phosphoanhydride bonds. They found in all kingdoms life, playing roles cell growth, infection, and blood coagulation. Unlike bacteria lower eukaryotes, the mammalian enzymes responsible for polyP metabolism largely unexplored. We use RNA sequencing (RNA-seq) mass spectrometry to define a broad impact produced inside cells via ectopic expression E. coli synthetase PPK. find that multiple cellular compartments can...
The RNA polymerase II (RNAP II)-associated protein (RPAP) 2 has been discovered through its association with various subunits of RNAP in affinity purification coupled mass spectrometry experiments. Here, we show that RPAP2 is a mainly cytoplasmic shuttles between the cytoplasm and nucleus. shuttling tightly nuclear import II, as silencing provokes abnormal accumulation space. Most notably, RPAP4/GPN1 retention Our results support model which enters nucleus returns to GTPase GPN1/RPAP4....
Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of unesterified cholesterol in late endosomal/lysosomal compartments. Mutations NPC1 protein are implicated 95% patients with NPC disease. The most prevalent mutation missense I1061T that occurs ∼ 15-20% alleles. In our study, an isobaric labeling-based quantitative analysis proteome NPC1(I1061T) primary fibroblasts when compared wild-type cells identified 281 differentially expressed...
Identification of protein-protein interactions (PPI) by affinity purification (AP) coupled with tandem mass spectrometry (AP-MS/MS) produces large data sets high rates false positives. This is in part because contamination at the AP level (due to gel contamination, nonspecific binding TAP columns context purification, insufficient etc.). In this paper, we introduce a Bayesian approach identify false-positive PPIs involving contaminants AP-MS/MS experiments. Specifically, propose confidence...
Rett syndrome (RTT) is a pervasive developmental disorder caused by mutations in MECP2. Complete loss of MECP2 function males causes congenital encephalopathy, neurodevelopmental arrest, and early lethality. Induced pluripotent stem cell (iPSC) lines from male patients harboring MECP2, along with control their unaffected fathers, give us an opportunity to identify some the earliest cellular molecular changes associated loss-of-function (LOF). We differentiated iPSC-derived neural progenitor...
To understand the mechanism of action a drug and assess its clinical usefulness viability, it is imperative that affinity for putative targets determined. When coupled to mass spectrometry (MS), energetics-based protein separation (EBPS) techniques, such as thermal shift assay, have shown great potential identify on proteome scale. Nevertheless, computational analyses assessing confidence drug–target predictions made by these methods remained tightly tied protocol under which data were...
Niemann-Pick type C (NPC) disease is an inherited, progressive neurodegenerative disorder principally caused by mutations in the NPC1 gene. NPC characterized accumulation of unesterified cholesterol late endosomes (LE) and lysosomes (Ly) (LE/Ly). Vorinostat, a histone deacetylase inhibitor (HDACi), restores homeostasis fibroblasts derived from patients; however, exact mechanism which Vorinostat level not known yet. In this study, we performed comparative proteomic profiling response...
Immunoprecipitation coupled to tandem mass spectrometry (IP-MS/MS) methods are often used identify protein–protein interactions (PPIs). While these approaches prone false positive identifications through contamination and antibody nonspecific binding, their results can be filtered using negative controls computational modeling. However, such filtering does not effectively detect false-positive when IP-MS/MS is performed on human plasma samples. Therein, proteins cannot overexpressed or...
In many bacteria, polyphosphate kinase (PPK) enzymes use ATP to synthesize (polyP) in response cellular stress. These chains of inorganic phosphates are joined by high-energy bonds and can reach hundreds residues length. PolyP plays diverse functions helping bacteria adjust changing environmental conditions. However, the molecular mechanisms underlying these poorly understood. eukaryotic cells, polyacidic serine- lysine-rich (PASK) motifs proteins mediate binding polyP chains. Whereas PASK...
Affinity purification combined with tandem mass spectrometry (AP-MS/MS) is a well-established method used to discover interaction partners for given protein of interest. Because most AP-MS/MS approaches are performed using the soluble fraction whole cell extracts (WCE), information about cellular compartments where interactions occur lost. More importantly, classical often fails identify that take place in nonsoluble cell, example, on chromatin or membranes; consequently, complexes less...