A5085060533- Molecular Biology Techniques and Applications
- Ion-surface interactions and analysis
- Single-cell and spatial transcriptomics
- Asthma and respiratory diseases
- Pluripotent Stem Cells Research
- X-ray Spectroscopy and Fluorescence Analysis
- Education Methods and Technologies
- Mass Spectrometry Techniques and Applications
- Sociology and Education Studies
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Advanced Proteomics Techniques and Applications
- Tuberculosis Research and Epidemiology
- Reproductive System and Pregnancy
- Advanced biosensing and bioanalysis techniques
- HIV Research and Treatment
- Linguistic Education and Pedagogy
- Pregnancy and preeclampsia studies
- Immune cells in cancer
- Eosinophilic Disorders and Syndromes
- Monoclonal and Polyclonal Antibodies Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Nuclear Physics and Applications
- Advanced X-ray and CT Imaging
- 3D Printing in Biomedical Research
Stanford University
2018-2025
Palo Alto University
2018
University of Duisburg-Essen
2016
McMaster University
2007-2009
Western University
2006
Université Laval
1994-2002
Institut Universitaire de Cardiologie et de Pneumologie de Québec
2001
Centre hospitalier de l'Université Laval
1999
Biotechnology Research Institute
1990-1992
Université de Montréal
1992
Understanding tissue structure and function requires tools that quantify the expression of multiple proteins while preserving spatial information. Here, we describe MIBI-TOF (multiplexed ion beam imaging by time flight), an instrument uses bright sources orthogonal time-of-flight mass spectrometry to image metal-tagged antibodies at subcellular resolution in clinical sections. We demonstrate quantitative, full periodic table coverage across a five-log dynamic range, 36 labeled simultaneously...
Abstract Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with maternal decidua promote a tissue microenvironment conducive artery remodelling (SAR) 1–3 . However, it remains matter of debate regarding which immune stromal cells participate these interactions this evolves respect gestational...
Abstract Immune checkpoint inhibition (ICI) has fundamentally changed cancer treatment. However, only a minority of patients with metastatic triple negative breast (TNBC) benefit from ICI, and the determinants response remain largely unknown. To better understand factors influencing patient outcome, we assembled longitudinal cohort tissue multiple timepoints, including primary tumor, pre-treatment on-treatment tumor 117 treated ICI (nivolumab) in phase II TONIC trial. We used highly...
Degradation of ubiquitinated proteins by 26 S proteasomes requires ATP hydrolysis, but it is unclear how the proteasomal ATPases are regulated and proteolysis, substrate deubiquitination, degradation, hydrolysis coordinated. Polyubiquitinated were shown to stimulate purified proteasomes, only if contain a loosely folded domain. If they not ubiquitinated, such did increase ATPase activity. However, so upon addition ubiquitin aldehyde, which mimics chain binds S-associated deubiquitinating...
Understanding the mechanisms of HIV tissue persistence necessitates ability to visualize microenvironments where infected cells reside; however, technological barriers limit our dissect cellular components these reservoirs. Here, we developed protein and nucleic acid in situ imaging (PANINI) simultaneously quantify DNA, RNA, levels within compartments. By coupling PANINI with multiplexed ion beam (MIBI), measured over 30 parameters across archival lymphoid tissues from healthy or simian...
SUMMARY Despite being heavily infiltrated by immune cells, tuberculosis (TB) granulomas often subvert the host response to Mycobacterium (Mtb) infection and support bacterial persistence. We previously discovered that human TB are enriched for immunosuppressive factors typically associated with tumor-immune evasion, raising intriguing possibility they promote tolerance infection. In this study, our goal was identify prime drivers establishing tolerogenic niche determine if magnitude of...
Escherichia coli isolates from septicemic or healthy chickens and turkeys Quebec were serotyped, examined genotypically by using DNA probes specific for the pil pap fimbrial systems aerobactin siderophore system, phenotypically lethality in day-old chicks, hemagglutination, serum resistance, production. Serogroups O78 O1 most common turkeys. pap+ associated with septicemia, chicks. Four of nine expressed P adhesin, whereas all negative adhesin. The pil+ genotype was septicemia resistance...
Asthma presents a variable clinical response to corticosteroids (CS). Because CS more likely act on inflammation than tissue remodeling, the presence of bronchial structural changes in certain asthmatics may explain their limited CS. Matrix metalloproteinase-9 (MMP-9) and its inhibitor, inhibitor metalloproteinase-1 (TIMP-1), are, respectively, involved inflammatory processes fibrogenic processes. Previous reports have suggested that MMP-9:TIMP-1 ratio reflect balance between these two...
Abstract Neurodegenerative disorders are characterized by phenotypic changes and hallmark proteopathies. Quantifying these in archival human brain tissues remains indispensable for validating animal models understanding disease mechanisms. We present a framework nanometer-scale, spatial proteomics with multiplex ion beam imaging (MIBI) capturing neuropathological features. MIBI facilitated simultaneous, quantitative of 36 proteins on hippocampus from individuals spanning cognitively normal...
Cellular organization and functions encompass multiple scales in vivo. Emerging high-plex imaging technologies are limited resolving subcellular biomolecular features. Expansion Microscopy (ExM) related techniques physically expand samples for enhanced spatial resolution, but challenging to be combined with enable integrative multiscaled tissue biology insights. Here, we introduce Expand comPRESS hydrOgels (ExPRESSO), an ExM framework that allows protein staining, physical expansion, removal...
Abstract The cellular mechanism and target cell affected by stromal microenvironments in augmenting hematopoietic specification from pluripotent human embryonic stem cells (hESCs) has yet to be evaluated. Here, contrast aorta-gonad-mesonephros-derived S62 cells, OP9 inhibit apoptosis also augment the proliferation of hemogenic precursors prospectively isolated embryoid bodies. In addition, stroma supported within primitive compartment inhibiting CD45+CD34+ committed lineage, but have no...
Approximately 5 million dengue virus-infected patients progress to a potentially life-threatening severe (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep profiling by mass cytometry of PBMCs collected longitudinally from progressors (SDp) uncomplicated (D) patients. While D is characterized early activation innate responses, in SDp there rapid expansion IgG-secreting plasma cells memory regulatory T cells....
Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) evolution, we applied spatial proteomics, transcriptomics, glycomics to 670 lesions from 310 adult pediatric patients. Single-cell analysis shows high B7H3+ cell prevalence in glioblastoma (GBM) pleomorphic xanthoastrocytoma (PXA), while gliomas, including cases, express targetable antigens less than 50% cells, potentially explaining trial...
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Microglia are implicated in aging, neurodegeneration, and Alzheimer's disease (AD). Traditional, low-plex, imaging methods fall short of capturing