A5039596172- Microfluidic and Bio-sensing Technologies
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Cancer, Hypoxia, and Metabolism
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
- 3D Printing in Biomedical Research
- Microfluidic and Capillary Electrophoresis Applications
- Metabolism, Diabetes, and Cancer
- Cancer Genomics and Diagnostics
- Cellular Mechanics and Interactions
- thermodynamics and calorimetric analyses
- Neuroscience and Neural Engineering
- Light effects on plants
- Genetic Associations and Epidemiology
- Immune cells in cancer
- Ion channel regulation and function
- Blood properties and coagulation
- Immune Response and Inflammation
- Immunotoxicology and immune responses
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Effects of Environmental Stressors on Livestock
- Advanced Fluorescence Microscopy Techniques
- Autophagy in Disease and Therapy
Broad Institute
2020-2023
Q-State Biosciences (United States)
2017-2020
Massachusetts Institute of Technology
2013-2017
Koch Institute for Integrative Cancer Research At MIT
2016
University of California, Los Angeles
2012
Metastasis requires the penetration of cancer cells through tight spaces, which is mediated by physical properties as well their interactions with confined environment. Various microfluidic approaches have been devised to mimic traversal in vitro measuring time required for pass a constriction. Although cell's passage expected depend on its deformability, measurements from existing are confounded size and frictional channel wall. Here, we introduce device that enables precise measurement (i)...
Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on single haploid reference genome. Here, we present the EN-TEx resource 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating catalog >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes less conserved...
Cell size, measured as either volume or mass, is a fundamental indicator of cell state. Far more tightly regulated than size density, the ratio between mass and volume, which can be used to distinguish populations even when appear remain constant. Here we expand upon previous method for measuring density involving suspended microchannel resonator (SMR). We introduce new device, dual SMR, high-precision instrument single-cell using two resonators connected by serpentine fluidic channel. The...
We present a method for direct non-optical quantification of dry mass, density and water mass single living cells in suspension. Dry are obtained simultaneously by measuring cell’s buoyant sequentially an H2O-based fluid D2O-based fluid. Rapid exchange intracellular H2O D2O renders the content neutrally both measurements, thus paired measurements yield material alone. Utilizing this same property rapid exchange, we also demonstrate mass. In population E. coli, these to estimate percent...
Abstract The potential for circulating tumor cells (CTCs) to elucidate the process of cancer metastasis and inform clinical decision-making has made their isolation great importance. However, CTCs are rare in blood universal properties with which identify them remain elusive. As technological advancements have single-cell deformability measurements increasingly routine, assessment physical distinctions between may provide insight into feasibility deformability-based methods identifying...
Research in the last few years have focused on use of three-dimensional (3D) fibrin construct to deliver growth factors and cells. Three-dimensional permeability porosity are important aspects for proper nutrient uptake, gas exchange, waste removal-factors that critical cell survival. We previously reported mechanical strength (stiffness) 3D constructs is dependent fibrinogen thrombin concentration. In this study, we established two new vitro models examine how composition affects final pore...
Cellular physical properties are important indicators of specific cell states. Although changes in individual biophysical parameters, such as size, density, and deformability, during cellular processes have been investigated great detail, relatively little is known about how they related. Here, we use a suspended microchannel resonator (SMR) to measure single-cell volume, passage time through narrow constriction populations cells subjected variety environmental stresses. Osmotic stress...
Cytokine regulation of lymphocyte growth and proliferation is essential for matching nutrient consumption with cell state. Here, we examine how cellular biophysical changes that occur immediately after factor depletion promote adaptation to reduced uptake. After withdrawal, uptake decreases, leading apoptosis. Bcl-xL expression prevents death, autophagy facilitating long-term survival. However, induction slow relative the reduction uptake, suggesting cells must engage additional adaptive...
The physical characteristics of the T cell receptor (TCR)–peptide-major histocompatibility complex (pMHC) interaction are known to play a central role in determining function initial stages adaptive immune response. State-of-the-art assays can probe kinetics this with single-molecular-bond resolution, but precision typically comes at cost low throughput, since complexity these measurements largely precludes “scaling up.” Here, we explore feasibility detecting specific TCR–pMHC interactions...
We present a method for direct non-optical quantification of dry mass, density and water mass single living cells in suspension.Dry are obtained simultaneously by measuring cell's buoyant sequentially an H 2 O-based fluid D fluid.Rapid exchange intracellular O renders the content neutrally both measurements, thus paired measurements yield material alone.Utilizing this same property rapid exchange, we also demonstrate mass.In population E. coli, these to estimate percent weight volume.We then...
ABSTRACT Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on single haploid reference genome. Here, we present the EN-TEx resource personal epigenomes, for ∼25 tissues and >10 assays in four donors (>1500 open-access genomic proteomic datasets, total). Each dataset mapped to matched, diploid genome, which has long-read phasing structural variants. The mappings enable us identify >1 million loci with...
The voltage-gated sodium channel Nav1.7 is a genetically validated target for pain; pharmacological blockers are promising as new class of nonaddictive therapeutics. search subtype selective inhibitors requires reliable, scalable, and sensitive assay. Previously, we developed an all-optical electrophysiology (Optopatch) Spiking HEK platform to study activity-dependent modulation in format compatible with high-throughput screening. In this study, benchmarked the Optopatch assay existing...
Abstract To facilitate growth and division, proliferating cells must duplicate their mass over the cell cycle. Glucose glutamine are most consumed nutrients by mammalian cells, but extent to which these other contribute directly has not been investigated. Using isotope labeled nutrients, we quantified fraction of derived from different fuels find that surprisingly neither glucose nor provide majority carbon present in cells. Instead, amino acids, at substantially lower rates, together...
Histone ChIP-seq is one of the primary methods for charting cellular epigenomic landscape, components which play a critical regulatory role in gene expression. Analyzing activity elements across datasets and cell types can be challenging due to shifting peak positions normalization artifacts resulting from, example, differing read depths, ChIP efficiencies, target sizes. Moreover, broad regions enrichment seen repressive histone marks often evade detection by commonly used callers. Here, we...