A5086112491- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Cancer Research and Treatments
- CAR-T cell therapy research
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Neuroendocrine Tumor Research Advances
- Monoclonal and Polyclonal Antibodies Research
- Glioma Diagnosis and Treatment
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Nutrition, Genetics, and Disease
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Axon Guidance and Neuronal Signaling
- Cancer Cells and Metastasis
- Adenosine and Purinergic Signaling
- Histone Deacetylase Inhibitors Research
- Advanced biosensing and bioanalysis techniques
- Glycosylation and Glycoproteins Research
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- Genomics and Chromatin Dynamics
University of Toronto
2016-2025
Hospital for Sick Children
2014-2025
SickKids Foundation
2024
McMaster University
1948-2024
Canada Research Chairs
2009-2024
University of New Brunswick
1999-2024
Institute for Biomedical Engineering
2020-2024
Donnelly College
2018-2023
Queen's University
2023
Laboratory of Molecular Genetics
2023
Abstract Biologists can now prepare and image thousands of samples per day using automation, enabling chemical screens functional genomics (for example, RNA interference). Here we describe the first free, open-source system designed for flexible, high-throughput cell analysis, CellProfiler. CellProfiler address a variety biological questions quantitatively, including standard assays count, size, per-cell protein levels) complex morphological cell/organelle shape or subcellular patterns DNA staining).
Vanadate and pervanadate (the complexes of vanadate with hydrogen peroxide) are two commonly used general protein-tyrosine phosphatase (PTP) inhibitors. These compounds also have insulin-mimetic properties, an observation that has generated a great deal interest study. Since careful kinetic study the inhibitors been lacking, we sought to analyze their mechanisms inhibition. Our results show is competitive inhibitor for PTP1B, Ki 0.38 ±; 0.02 μM. EDTA, which known chelate vanadate, causes...
Abstract The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study human functional genomics. Pooled libraries CRISPR guide RNAs (gRNAs) targeting protein-coding genes and encoded in viral vectors have been used systematically create gene knockouts a variety cancer immortalized lines, an effort identify whether these cause cellular fitness defects. Previous work has shown that screens are more sensitive specific than pooled-library shRNA similar assays, but...
Many biological pathways were first uncovered by identifying mutants with visible phenotypes and scoring every sample in a screen via tedious subjective visual inspection. Now, automated image analysis can effectively score many phenotypes. In practical application, customizing an image-analysis algorithm or finding sufficient number of example cells to train machine learning be infeasible, particularly when positive control samples are not available the phenotype interest is rare. Here we...
Genomic analyses are yielding a host of new information on the multiple genetic abnormalities associated with specific types cancer. A comprehensive description cancer-associated can improve our ability to classify tumors into clinically relevant subgroups and, occasion, identify mutant genes that drive cancer phenotype ("drivers"). More often, though, functional significance mutations is difficult discern. Genome-wide pooled short hairpin RNA (shRNA) screens enable global identification...
The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination protein substrates. used massively diverse combinatorial libraries variants develop inhibitors four deubiquitinases (DUBs) and analyzed DUB-inhibitor complexes with crystallography. extended selection strategy conjugating (E2) ligase (E3) found can also enhance enzyme activity. Last, we showed bind selectively ubiquitin-binding domains....