A5004316519- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Cell Image Analysis Techniques
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Genetics, Bioinformatics, and Biomedical Research
- Advanced biosensing and bioanalysis techniques
- Gut microbiota and health
- Cancer Cells and Metastasis
- SARS-CoV-2 detection and testing
- Renal and related cancers
- Cholesterol and Lipid Metabolism
- RNA Interference and Gene Delivery
- Dietary Effects on Health
- Ferroptosis and cancer prognosis
- Respiratory viral infections research
- Mathematical Biology Tumor Growth
California Institute of Technology
2022-2025
University of Pennsylvania
2017-2024
California University of Pennsylvania
2018-2022
University of California, Los Angeles
2013-2015
UCLA Health
2015
Genetics provides a potentially powerful approach to dissect host-gut microbiota interactions. Toward this end, we profiled gut using 16s rRNA gene sequencing in panel of 110 diverse inbred strains mice. This has previously been studied for wide range metabolic traits and can be used high-resolution association mapping. Using SNP-based with linear mixed model, estimated the heritability composition. We conclude that, controlled environment, genetic background accounts substantial fraction...
Abstract Gene expression states persist for varying lengths of time at the single-cell level, a phenomenon known as gene memory. When cells switch states, losing memory their prior state, this transition can occur in absence genetic changes. However, we lack robust methods to find regulators or track state switching. Here, develop lineage tracing-based technique quantify and identify that states. Applied melanoma without therapy, long-lived fluctuations are predictive later resistance...
The widespread coronavirus disease 2019 (COVID-19) is caused by infection with the novel SARS-CoV-2. Currently, we have limited understanding of which cells become infected SARS-CoV-2 in human tissues and where viral RNA localizes on subcellular level. Here, present a platform for preparing autopsy tissue visualizing using fluorescence situ hybridization (FISH) amplification chain reaction. We developed probe sets that target different regions (including ORF1a N), as well specifically...
The nucleus is highly organized such that factors involved in transcription and processing of distinct classes RNA are within specific nuclear bodies. One body the speckle, which defined by high concentrations protein non-coding regulators pre-mRNA splicing. What functional role, if any, speckles might play process mRNA splicing remains unknown. Here we show genes localized near display higher spliceosome concentrations, increased binding to their pre-mRNAs, co-transcriptional levels...
Abstract Even amongst genetically identical cancer cells, therapy resistance often only emerges from a very small subset of those cells. Much effort has gone into uncovering the molecular differences in rare individual cells initial population that may allow certain to become resistant; however, comparatively little is known about variability resistant outcomes themselves. Here, we develop and apply FateMap, framework combines DNA barcoding with single-cell RNA sequencing reveal fates...
Cardiac differentiation of human-induced pluripotent stem (hiPS) cells consistently produces a mixed population cardiomyocytes and non-cardiac cell types, even when using well-characterized protocols. We sought to determine whether different types might result from intrinsic differences in hiPS prior the onset differentiation.
Summary Many biological signaling pathways employ proteins that competitively dimerize in diverse combinations. These dimerization networks can perform biochemical computations, which the concentrations of monomers (inputs) determine dimers (outputs). Despite their prevalence, little is known about range input-output computations (their “expressivity”) and how it depends on network size connectivity. Using a systematic computational approach, we demonstrate even small (3-6 monomers) are...
Abstract Plasticity enables cells to change their gene expression state in the absence of a genetic change. At single-cell level, these states can persist for different lengths time which is quantitative measurement referred as memory. Because plasticity not encoded by changes, cell be reversible, and therefore, are amenable modulation disrupting However, we currently do have robust methods find regulators memory or track switching plastic populations. Here, developed lineage tracing-based...
Two different cell signals often affect transcription of the same gene. In such cases, it is natural to ask how combined transcriptional response compares individual responses. The most commonly used mechanistic models predict additive or multiplicative responses, but a systematic genome-wide evaluation these predictions not available. Here, we analyzed human MCF-7 cells retinoic acid and TGF-β, applied individually in combination. responses induced genes exhibited range behaviors, clearly...
Pluripotency can be induced in somatic cells by the expression of four "Yamanaka" factors OCT4, KLF4, SOX2, and MYC. However, even homogeneous conditions, usually only a rare subset admit reprogramming, molecular characteristics this remain unknown. Here, we apply retrospective clone tracing to identify characterize individual human fibroblast that are primed for reprogramming. These fibroblasts showed markers increased cell cycle speed decreased activation. Knockdown activation factor...
The goal of these studies was to determine the effect 5,6-epoxyisoprostane, EI, on human aortic endothelial cells (HAEC). EI can form as a phospholipase product 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine, PEIPC, proinflammatory molecule that accumulates in sites inflammation where phospholipases are also increased. To HAEC, we synthesized several stereoisomers using convergent approach from individual optically pure building blocks, epoxyaldehydes 5 and 6 bromoenones...
Abstract Non-genetic factors can cause individual cells to fluctuate substantially in gene expression levels over time. Yet it remains unclear whether these fluctuations persist for much longer than the time of one cell division. Current methods measuring single mostly rely on point measurements, making duration or cellular memory difficult measure. Here, we report a method combining Luria and Delbrück’s fluctuation analysis with population-based RNA sequencing (MemorySeq) identifying genes...
Abstract Cellular plasticity describes the ability of cells to transition from one set phenotypes another. In context cancer therapeutics, refers transient fluctuations in molecular state tumor cells, driving formation rare primed survive drug treatment and ultimately reprogram into a stably resistant fate. However, biological processes governing this cellular remain unknown. We used CRISPR/Cas9 genetic screens reveal genes that affect cell fate decisions by altering across range functional...