A5002484166- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Cancer Cells and Metastasis
- Advanced Fluorescence Microscopy Techniques
- Cell Adhesion Molecules Research
- Cell Image Analysis Techniques
- bioluminescence and chemiluminescence research
- Cancer Genomics and Diagnostics
- Nuclear Structure and Function
- Hippo pathway signaling and YAP/TAZ
- RNA modifications and cancer
- Brain Metastases and Treatment
- Radiopharmaceutical Chemistry and Applications
- Wnt/β-catenin signaling in development and cancer
- Immune Response and Inflammation
- Force Microscopy Techniques and Applications
- Structural Analysis and Optimization
- Cancer Diagnosis and Treatment
- Microfluidic and Capillary Electrophoresis Applications
- Ubiquitin and proteasome pathways
- 3D Printing in Biomedical Research
- Ion channel regulation and function
- Microfluidic and Bio-sensing Technologies
- Adenosine and Purinergic Signaling
- Erythrocyte Function and Pathophysiology
Johns Hopkins University
2022-2024
National Institute of Dental and Craniofacial Research
2023-2024
National Institutes of Health
2023-2024
McGill University
2017-2023
McGill University Health Centre
2020
Abstract Cells respond to physical stimuli, such as stiffness 1 , fluid shear stress 2 and hydraulic pressure 3,4 . Extracellular viscosity is a key cue that varies under physiological pathological conditions, cancer 5 However, its influence on biology the mechanism by which cells sense changes in are unknown. Here we demonstrate elevated counterintuitively increases motility of various cell types two-dimensional surfaces confinement, dissemination from three-dimensional tumour spheroids....
Fluorescence illumination can cause phototoxicity that negatively affects living samples. This study demonstrates much of the and photobleaching experienced with live-cell fluorescence imaging occurs as a result 'illumination overhead' (IO). when sample is illuminated but emission not being captured by microscope camera. Several technological advancements have been developed, including fast-switching LED lamps transistor-transistor logic (TTL) circuits, to diminish caused IO. These are...
Abstract Cell migration regulates diverse (patho)physiological processes, including cancer metastasis. According to the Osmotic Engine Model, polarization of NHE1 at leading edge confined cells facilitates water uptake, cell protrusion and motility. The physiological relevance Model identity molecules mediating rear shrinkage remain elusive. Here, we demonstrate that SWELL1 preferentially polarize trailing edges, respectively, mediate volume regulation, dissemination from spheroids...
Cells tune adherens junction dynamics to regulate epithelial integrity in diverse (patho)physiological processes, including cancer metastasis. We hypothesized that the spatially confining architecture of peritumor stroma promotes metastatic cell dissemination by remodeling cell-cell adhesive interactions. By combining microfluidics with live-cell imaging, FLIM/FRET biosensors, and optogenetic tools, we show confinement induces leader dissociation from cohesive ensembles. Cell is triggered...
Abstract Background Compared to minimally invasive brain metastases (MI BrM), highly (HI) lesions form abundant contacts with cells in the peritumoral parenchyma and are associated poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether BrM invasion pattern is influenced pSTAT3+ RAs may serve predictive biomarker inhibition. Methods We used immunohistochemistry identify HI MI...
Cytoskeleton-mediated force transmission regulates nucleus morphology. How nuclei shaping occurs in fibrous vivo environments remains poorly understood. Here suspended nanofiber networks of precisely tunable (nm-µm) diameters are used to quantify plasticity mimicking the natural extracellular matrix. Contrary apical cap over cells on 2-dimensional surfaces, cytoskeleton fibers displays a uniform actin network caging nucleus. The role contractility-driven sculpting nuclear shapes is...
ABSTRACT The genetic alterations contributing to migration proficiency, a phenotypic hallmark of metastatic cells required for colonizing distant organs, remain poorly defined. Here, we used single-cell magneto-optical capture (scMOCa) isolate fast from heterogeneous human breast cancer cell populations, based on their migratory ability alone. We show that captured subpopulations retain higher speed and focal adhesion dynamics over many generations as result motility-related transcriptomic...
The p66ShcA redox protein is the longest isoform of Shc1 gene and variably expressed in breast cancers. In response to a variety stress stimuli, becomes phosphorylated on serine 36, which allows it translocate from cytoplasm mitochondria where stimulates formation reactive oxygen species (ROS). Conflicting studies suggest both pro- anti-tumorigenic functions for p66ShcA, prompted us examine contribution tumor cell-intrinsic during cancer metastasis.We tested whether impacts lung-metastatic...
Abstract Cells migrating in confinement experience mechanical challenges whose consequences on cell migration machinery remain only partially understood. Here, we demonstrate that a pool of the cytokinesis regulatory protein anillin is retained during interphase cytoplasm different types. Confinement induces recruitment cytoplasmic to plasma membrane at poles cells, which further enhanced upon nuclear envelope (NE) rupture(s). Rupture events also enable egress predominantly RhoGEF Ect2....
SHC adaptor protein (SHCA) and lipoma-preferred partner (LPP) mediate transforming growth factor β (TGFβ)-induced breast cancer cell migration invasion. Reduced expression of either diminishes lung metastasis, but the reason for this effect is unclear. Here, using total internal reflection fluorescence (TIRF) microscopy, we found that TGFβ enhanced assembly disassembly rates paxillin-containing adhesions in an SHCA-dependent manner through phosphorylation specific SHCA tyrosine residues...
Abstract:
Polysialic acid (polySia) is a post-translational modification of select group cell-surface proteins that guides cellular interactions. As the overall impact changes in expression this glycan on leukocytes during infection not known, we evaluate immune response polySia-deficient ST8SiaIV−/− mice infected with Streptococcus pneumoniae (Spn). Compared wild-type (WT) mice, are less susceptible to and clear Spn from airways faster, alveolar macrophages demonstrating greater viability phagocytic...
Abstract Introduction: Src homology and collagen A (ShcA) adaptor proteins are essential during breast cancer progression. However, the role of largest isoform, p66ShcA, is conflicting still poorly understood. Under high levels stress p66ShcA phosphorylated on serine36, within its CH2 domain, allowing it to translocate mitochondria induce formation reactive oxygen species (ROS) promote apoptosis. Previously, we provided first in vivo evidence that can influence both pro anti-tumorigenic...
Additional file 5: Figure S5. p66ShcA does not alter the mesenchymal properties of 4T1-derived triple negative breast cancers. (A) Immunoblot analysis whole cell lysates isolated from 4T1-537 parental, p66-CR (VC), (WT) and (S36A) mammary tumors (n = 18 each) using ShcA-, E-Cadherin, Vimentin Tubulin-specific antibodies. (B-D) Densitometric quantification shown in panel A for (B) p66ShcA/Tubulin, (C) p66ShcA/p52ShcA, (D) E-Cadherin/Tubulin (E) Vimentin/Tubulin ratios. The data is normalized...
ABSTRACT First Person is a series of interviews with the first authors selection papers published in Journal Cell Science, helping early-career researchers promote themselves alongside their papers. Alexander Kiepas author on ‘ Optimizing live-cell fluorescence imaging conditions to minimize phototoxicity’, JCS. PhD student lab Dr Claire Brown and Peter Siegel (co-supervised) at McGill University, Québec, Canada, investigating breast cancer metastasis biophysical tools.