A5078934880- Cellular Mechanics and Interactions
- Developmental Biology and Gene Regulation
- Cell Image Analysis Techniques
- Hippo pathway signaling and YAP/TAZ
- AI in cancer detection
- Medical Image Segmentation Techniques
- Microtubule and mitosis dynamics
- 3D Printing in Biomedical Research
- Neurobiology and Insect Physiology Research
- Wnt/β-catenin signaling in development and cancer
- Marine Biology and Environmental Chemistry
- Tendon Structure and Treatment
- Planarian Biology and Electrostimulation
- Silk-based biomaterials and applications
- Wound Healing and Treatments
- Cancer Cells and Metastasis
- Radiomics and Machine Learning in Medical Imaging
- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Biocrusts and Microbial Ecology
- Cardiomyopathy and Myosin Studies
- Pluripotent Stem Cells Research
- Advanced Fluorescence Microscopy Techniques
- Force Microscopy Techniques and Applications
- RNA Research and Splicing
University of Toronto
2016-2025
Ted Rogers Centre for Heart Research
2016-2025
Hospital for Sick Children
2015-2025
SickKids Foundation
2022-2023
Biologie du Développement et Cellules Souches
2015-2022
ORCID
2022
Laurentian University
2021
University of Alberta
2021
Western University
2021
Toronto Public Health
2015
Abstract In this article, we present a novel method for the automatic 3D reconstruction of thick tissue blocks from 2D histological sections. The algorithm completes high‐content (multiscale, multifeature) imaging system simultaneous morphological and molecular analysis samples. This computer‐based integrates image acquisition, annotation, registration, three‐dimensional reconstruction. We an experimental validation tool using both synthetic real data. particular, entire mouse mammary gland...
Contractile forces generated by the actomyosin cytoskeleton within individual cells collectively generate tissue-level force during epithelial morphogenesis. During Drosophila mesoderm invagination, pulsed meshwork contractions and a ratchet-like stabilization of cell shape drive apical constriction. Here, we investigate how contractile are integrated across tissue. Reducing adherens junction (AJ) levels or ablating meshworks causes tissue-wide tears, which release tension that is...
Fluctuations in the size of apical cell surface have been associated with constriction and tissue invagination. However, it is currently not known if oscillatory behaviors are a unique property constricting cells or they constitute universal feature force balance between multicellular tissues. Here, we set out to determine whether occur parallel intercalation during morphogenetic process axis elongation Drosophila embryo. We applied multi-color, time-lapse imaging living embryos SIESTA, an...
How position-dependent cell fate acquisition occurs during embryogenesis is a central question in developmental biology. To study this process, we developed defined, high-throughput assay to induce peri-gastrulation-associated patterning geometrically-confined human pluripotent stem (hPSC) colonies. We observed that, upon BMP4 treatment, phosphorylated SMAD1 (pSMAD1) activity the colonies organized into radial gradient. Reaction-Diffusion (RD) based computational model and that...
Axis elongation is a conserved process in which the head-to-tail or anterior-posterior (AP) axis of an embryo extends. In Drosophila, cellular rearrangements drive elongation. Cells exchange neighbours by converging into transient multicellular vertices resolve through assembly new cell interfaces parallel to AP axis. We found that elongate pulses correlated with periodic contractions surrounding cells. Inhibiting actomyosin contractility globally, specifically cells around vertices,...
α-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to actin cytoskeleton at adherens junctions (AJs). However, molecular mechanisms by which engages F-actin under tension remained elusive. Here we show α1-helix of actin-binding domain (αcat-ABD) mechanosensing motif regulates tension-dependent binding and bundling. αcat-ABD containing an α1-helix-unfolding mutation (H1) shows enhanced in vitro. Although...
Embryonic epithelia have a remarkable ability to rapidly repair wounds. A supracellular actomyosin cable around the wound coordinates cellular movements and promotes closure. Actomyosin formation is accompanied by junctional rearrangements at margin. We used in vivo time-lapse quantitative microscopy show that clathrin, dynamin, ADP-ribosylation factor 6, three components of endocytic machinery, accumulate wounds Drosophila melanogaster embryos process requires calcium signaling...
Epithelial–mesenchymal transitions play key roles in development and cancer entail the loss of epithelial polarity cell adhesion. In this study, we use quantitative live imaging ingressing neuroblasts (NBs) Drosophila melanogaster embryos to assess apical domain junctional disassembly. Ingression is independent Snail family transcriptional repressors down-regulation E-cadherin (DEcad) transcription. Instead, posttranscriptionally regulated decrease DEcad coincides with reduction contact...
Epithelial tissues are protective barriers that display a remarkable ability to repair wounds. Wound is often associated with an accumulation of actin and nonmuscle myosin II around the wound, forming purse string. The role actomyosin networks in generating mechanical force during wound not well understood. Here we investigate mechanisms generation epidermis early late Drosophila embryos. We find closure faster embryos, where, addition string at medial cortex wounded cells contribute rapid...
Tissue morphogenesis relies on the coordinated action of actin networks, cell-cell adhesions, and cell-extracellular matrix (ECM) adhesions. Such coordination can be achieved through cross-talk between cell-ECM Drosophila dorsal closure (DC), a morphogenetic process in which an extraembryonic tissue called amnioserosa contracts ingresses to close discontinuity epidermis embryo, requires both However, whether functions these two types adhesions are during DC is not known. Here we analyzed...
ABSTRACT Embryos repair epithelial wounds rapidly in a process driven by collective cell movements. Upon wounding, actin and the molecular motor non-muscle myosin II are redistributed cells adjacent to wound, forming supracellular purse string around lesion. Purse contraction coordinates movements drives rapid wound closure. By using fluorescence recovery after photobleaching Drosophila embryos, we found that turns over as contracts. Myosin turnover at was slower than other actomyosin...
α-catenin is a key protein of adherens junctions (AJs) with mechanosensory properties. It also acts as tumor suppressor that limits tissue growth. Here we analyzed the function Drosophila α-Catenin (α-Cat) in growth regulation wing epithelium. We found different α-Cat levels led to differential activation Hippo/Yorkie or JNK signaling causing overgrowth degeneration, respectively. can modulate Yorkie-dependent through recruitment Ajuba, negative regulator Hippo AJs but mechanism independent...
Embryos extend their anterior-posterior (AP) axis in a conserved process known as elongation. Drosophila elongation occurs an epithelial monolayer, the germband, and is driven by cell intercalation, shape changes, oriented divisions at posterior germband. Anterior germband cells also divide during We developed image analysis pattern-recognition methods to track dividing from confocal microscopy movies generally applicable approach. Mesectoderm cells, forming ventral midline, divided parallel...
Vascular calcification is a pathology characterized by arterial mineralization, which common late-term complication of atherosclerosis that independently increases the risk adverse cardiovascular events fourfold. A major source calcifying cells transdifferentiating vascular smooth muscle (VSMCs). Previous studies showed deletion collagen-binding receptor, DDR1 (discoidin domain receptor-1), attenuated VSMC calcification. Increased matrix stiffness drives osteogenesis, and has been implicated...
Abstract The sarco-endoplasmic reticulum (SR/ER) plays an important role in the development and progression of many heart diseases. However, aspects its structural organization remain largely unknown, particularly cells with a highly differentiated SR/ER network. Here, we report cardiac enriched, membrane protein, REEP5 that is centrally involved regulating cellular stress responses myocytes. In vitro depletion mouse myocytes results destabilization luminal vacuolization along decreased...