A5004984001- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Cancer Cells and Metastasis
- 3D Printing in Biomedical Research
- Force Microscopy Techniques and Applications
- Neonatal Respiratory Health Research
- Spaceflight effects on biology
- Advanced Fluorescence Microscopy Techniques
- Angiogenesis and VEGF in Cancer
- Wnt/β-catenin signaling in development and cancer
- Single-cell and spatial transcriptomics
- Biocrusts and Microbial Ecology
- Cancer Genomics and Diagnostics
- Infant Nutrition and Health
- Heat shock proteins research
- Autophagy in Disease and Therapy
- Genetics, Bioinformatics, and Biomedical Research
- Skin and Cellular Biology Research
- Microfluidic and Bio-sensing Technologies
- Advanced biosensing and bioanalysis techniques
- Teaching and Learning Programming
- Blood properties and coagulation
- Lipid Membrane Structure and Behavior
- Digestive system and related health
- Lattice Boltzmann Simulation Studies
University of California, San Francisco
2016-2025
Johns Hopkins Medicine
2012-2019
Johns Hopkins University
2012-2019
Tissue folds are structural motifs critical to organ function. In the intestine, bending of a flat epithelium into periodic pattern gives rise villi, finger-like protrusions that enable nutrient absorption. However, molecular and mechanical processes driving villus morphogenesis remain unclear. Here, we identify an active mechanism simultaneously patterns intestinal initiate formation. At cellular level, find PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces...
Myosin II is a central mechanoenzyme in wide range of cellular morphogenic processes. Its localization dependent not only on signal transduction pathways, but also mechanical stress. We suggest that this stress-dependent distribution the result both force-dependent binding to actin filaments and cooperative interactions between bound myosin heads. By assuming heads induces and/or stabilizes local conformational changes enhances locally, we successfully simulate observed experimentally. In...
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Cigarette smoke (CS) drives development progression. The epithelial barrier damaged by CS with increased monolayer permeability. However, the molecular changes that this disruption interaction between adhesion proteins cytoskeleton are not well defined. We hypothesized alters integrity increasing cell contractility decreasing in epithelia. Normal human airway cells primary COPD were exposed to air or...
The mechanical properties of cells change with their differentiation, chronological age, and malignant progression. Consequently, these may be useful label-free biomarkers various functional or clinically relevant cell states. Here, we demonstrate mechano-node-pore sensing (mechano-NPS), a multi-parametric single-cell-analysis method that utilizes four-terminal measurement the current across microfluidic channel to quantify simultaneously diameter, resistance compressive deformation,...
Abstract In breast cancer (BC), radial alignment of collagen fibers at the tumor-matrix interface facilitates collective invasion cells into surrounding stromal matrix, a critical step toward metastasis. Collagen remodeling is driven by proteases and cellular forces, mediated matrix mechanical plasticity, or irreversible deformation in response to force. However, specific mechanisms causing remain unclear. Here, we study BC tumor spheroids collagen-rich matrices. Increasing plasticity...
EPH/EPHRIN signaling is essential to many aspects of tissue self-organization and morphogenesis, but little known about how regulates cell mechanics during these processes. Here, we use a series approaches examine drives cellular self-organization. Contact angle measurements reveal that decreases the stability heterotypic cell:cell contacts through increased cortical actomyosin contractility. We find EPH/EPHRIN-driven segregation depends on contractility occurs independently directed...
Migrating cells can extend their leading edge by forming myosin-driven blebs and F-actin-driven pseudopods. When coerced to migrate in resistive environments, Dictyostelium switch from using predominately pseudopods blebs. Bleb formation has been shown be chemotactic influenced the direction of gradient. In this study, we determine blebbing responses developed discoideum cAMP gradients varying steepness produced microfluidic channels with different confining heights, ranging between 1.7 μm...
Aquaporin-5 (AQP5) is a water-specific channel located on the apical surface of airway epithelial cells. In addition to regulating transcellular water permeability, AQP5 can regulate paracellular though mechanisms by which this occurs have not been determined. Microtubules also permeability. Here, we report that promotes microtubule assembly and helps maintain assembled steady state levels with slower turnover dynamics in Specifically, reduced correlated lower microtubules decreased...
Organoids are powerful models of tissue physiology, yet their applications remain limited due to relatively simple morphology and high organoid-to-organoid structural variability. To address these limitations we developed a soft, composite yield-stress extracellular matrix that supports optimal organoid morphogenesis following freeform 3D bioprinting cell slurries at tissue-like densities. The material is designed with two temperature regimes: 4 °C it exhibits reversible behavior support...
The composite of the actin cytoskeleton and plasma membrane plays important roles in many biological events. Here, we employed emulsion method to synthesize artificial cells with biomimetic cortex vesicles characterized their mechanical properties. We demonstrated that provides flexibility adjust lipid composition protein concentrations achieve desired size distribution, internal microstructure, Moreover, comparison cortical elasticity measured for reconstituted real cells, including those...
Cellular contractility is governed by a control system of proteins that integrates internal and external cues to drive diverse shape change processes. This controller includes myosin II motors, actin crosslinkers protein scaffolds, which exhibit robust cooperative mechanoaccumulation. However, the biochemical interactions feedback mechanisms remain unknown. Here, we use proteomics approach identify direct interactors two key nodes in social amoeba Dictyostelium discoideum: crosslinker...
Internships are an effective way of connecting high school students in a meaningful manner to the sciences. Disadvantaged minorities have fewer opportunities participate internships, and underrepresented both science, technology, engineering, mathematics majors careers. We developed Summer Academic Research Experience (SARE) program that provides enriching academic internship youth. Our has shown successful for these disadvantaged youth, several issues need be addressed addition scientific...
ABSTRACT We describe MULTI-seq: A rapid, modular, and universal scRNA-seq sample m ultiplexing strategy u sing l ipid- t agged i ndices. MULTI-seq reagents can barcode any cell type from species with an accessible plasma membrane. The method is compatible enzymatic tissue dissociation, also preserves viability endogenous gene expression patterns. leverage these features to multiplex the analysis of multiple solid tissues comprising human mouse cells isolated patient-derived xenograft models....
Tissues comprise ordered arrangements of cells that can be surprisingly disordered in their details. How the properties single and microenvironment contribute to balance between order disorder at tissue-scale remains poorly understood. Here, we address this question using self-organization human mammary organoids as a model. We find behave like dynamic structural ensemble steady state. apply maximum entropy formalism derive distribution from three measurable parameters - degeneracy states,...
Tissue folding generates structural motifs critical to organ function. In the intestine, bending of a flat epithelium into periodic pattern folds gives rise villi, numerous finger-like protrusions that are essential for nutrient absorption. However, molecular and mechanical mechanisms driving initiation morphogenesis villi remain matter debate. Here, we identify an active mechanism simultaneously patterns intestinal villi. We find PDGFRA+ subepithelial mesenchymal cells generate myosin...
The construction of three-dimensional (3D) microvascular networks with defined structures remains challenging. Emerging bioprinting strategies provide a means patterning endothelial cells (ECs) into the geometry 3D networks, but microenvironmental cues necessary to promote their self-organization cohesive and perfusable microvessels are not well known. To this end, we reconstituted microvessel formation in vitro by thin lines closely packed ECs fully embedded within extracellular matrix...
Abstract The construction of three-dimensional (3D) microvascular networks with defined structures remains challenging. Emerging bioprinting strategies provide a means patterning endothelial cells (ECs) into the geometry 3D networks, but microenvironmental cues necessary to promote their self-organization cohesive and perfusable microvessels are unknown. To this end, we reconstituted microvessel formation in vitro by thin lines closely packed ECs fully embedded within extracellular matrix...
ABSTRACT BACKGROUND AND AIMS Methotrexate is an important tool in the arsenal of oncologists, gastroenterologists, and rheumatologists. At low doses it induces intestinal barrier dysfunction that may induce side effects such as gastrointestinal discomfort liver injury. Previous studies suggest lactoferrin can improve function a variety contexts. This study set out to determine mechanism methotrexate induced assess effect other components human breast milk on this dysfunction. METHODS Using...