A5005802142- Single-cell and spatial transcriptomics
- Bacteriophages and microbial interactions
- Adipose Tissue and Metabolism
- Plant Virus Research Studies
- Legume Nitrogen Fixing Symbiosis
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Gene expression and cancer classification
- Evolution and Genetic Dynamics
- SARS-CoV-2 and COVID-19 Research
- Gene Regulatory Network Analysis
- Muscle Physiology and Disorders
- Exercise and Physiological Responses
- COVID-19 Clinical Research Studies
- Genetics and Physical Performance
- Genomics and Chromatin Dynamics
- Viral gastroenteritis research and epidemiology
- Cell Image Analysis Techniques
- Congenital heart defects research
- Advanced Fluorescence Microscopy Techniques
- SARS-CoV-2 detection and testing
- COVID-19 epidemiological studies
- Molecular Biology Techniques and Applications
- Bioinformatics and Genomic Networks
- Genomics and Phylogenetic Studies
Icahn School of Medicine at Mount Sinai
2016-2024
Lakeland College
2020
University of Tasmania
2020
Carnegie Mellon University
2012-2016
Reckitt Benckiser (United States)
2010
Saint Mary's College of California
1999-2009
University of Oregon
2002
Abstract Skeletal muscle is a heterogeneous tissue comprised of fiber and mononuclear cell types that, in addition to movement, influences immunity, metabolism cognition. We investigated the gene expression patterns skeletal cells using RNA-seq subtype-pooled single human fibers from vastus lateralis, mouse quadriceps, diaphragm. identified 11 types, including two fibro-adipogenic progenitor (FAP) subtypes. The FBN1+ FAP subtype novel corresponding type was also found analysis mouse....
Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood
Significance Tissue-resident macrophages can arise from multiple origins during embryonic and adult hematopoiesis. They are important cells regulating a wide range of biological processes, such as tissue remodeling organogenesis, homeostasis in the steady state, repair following injury, immune response to pathogens. Although tissue-specific functions resident have been extensively studied many other tissues, they not well characterized skeletal muscle. Our study origins, gene expression,...
Early interactions of influenza A virus (IAV) with respiratory epithelium might determine the outcome infection. The study global cellular innate immune responses often masks multiple aspects mechanisms by which populations cells work as organized and heterogeneous systems to defeat infection, how counteracts these systems. In this study, we experimentally dissected dynamics IAV human epithelial cell interaction during early infection at single-cell level. We found that number viruses...
Abstract To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq snATACseq datasets individual animals highlight continuum between developmental epigenetically-encoded cell types transcriptionally-determined transient states. Co-accessibility analysis-based identification putative Fshb cis-regulatory domain...
Despite their importance in tissue homeostasis and renewal, human pituitary stem cells (PSCs) are incompletely characterized. We describe a single nucleus RNA-seq ATAC-seq resource from pediatric, adult, aged postmortem pituitaries (snpituitaryatlas.princeton.edu) characterize cell-type-specific gene expression chromatin accessibility programs for all major cell lineages. identify uncommitted PSCs, committing progenitor cells, sex differences. Pseudotime trajectory analysis indicates that...
Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, RNA-seq datasets from eight control endurance exercise-trained (EET) rats. Integration of baseline mapped gene location dependence epigenetic features identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks EET showed little overlap...
ABSTRACT The Rho-type GTPase, Cdc42, has been implicated in a variety of functions the yeast life cycle, including septin organization for cytokinesis, pheromone response, and haploid invasive growth. A group proteins called GTPase-activating (GAPs) catalyze hydrolysis GTP to GDP, thereby inactivating Cdc42. At time this study began, there was one known GAP, Bem3, putative Rga1, We identified another GAP Cdc42 named it Rga2 (Rho protein 2). confirmed by genetic biochemical criteria that...
The mRNA-1273 vaccine is effective against SARS-CoV-2 and was granted emergency use authorization by the FDA. Clinical studies, however, cannot provide controlled response to infection complex immunological insight that are only possible with preclinical studies. Hamsters model reliably exhibits severe disease similar in hospitalized patients, making them pertinent for evaluation. We demonstrate prime or prime-boost administration of hamsters elicited robust neutralizing antibodies,...
Virus capsid assembly has been widely studied as a biophysical system, both for its biological and medical significance an important model complex self-assembly processes. No current technology can monitor in detail what information we have on kinetics comes exclusively from vitro studies. There are many differences between the intracellular environment that of assay, however, might be expected to alter pathways. Here, explore one specific feature characteristic known large effects...
Chromatin accessibility is a key factor influencing gene expression. We optimized the Omni-ATAC-seq protocol and used it together with RNA-seq to investigate cis-regulatory elements in rat white adipose skeletal muscle, two tissues contrasting metabolic functions. While promoter correlated RNA expression, integration of datasets identified tissue-specific differentially accessible regions (DARs) that predominantly localized intergenic intron regions. DARs were mapped expressed (DE) genes...
Virus capsid assembly has attracted considerable interest from the biophysical modeling community as a model system for complicated self-assembly processes. Simulation methods have proven valuable characterizing space of possible kinetics and mechanisms assembly, but they so far been able to say little about or pathways any specific virus. It is not directly measure detailed interaction rates needed parameterize model, there only limited amount experimental evidence available constrain...
Fibrosis is a prominent pathological feature of skeletal muscle in Duchenne muscular dystrophy (DMD). The commonly used disease mouse model, mdx5cv , displays progressive fibrosis the diaphragm but not limb muscles. We use single-cell RNA sequencing to determine cellular expression genes involved extracellular matrix (ECM) production and degradation quadriceps. find that fibro/adipogenic progenitors (FAPs) are only primary source ECM also predominant cells express important regulatory genes,...
OVERVIEW:Heightened expectations for growth from internal technology suggest a requirement to improve the productivity of "fuzzy front-end" innovation process. Its description as an organizational process should mesh with that product development, characterized by "stage-gate" concurrent engineering. With this in mind, "Front-End Innovation Process" (FEIP) was established, first at AlliedSignal and later Alcoa. Both processes were designed meet business objectives be able drive...
Abstract Regular exercise promotes whole-body health and prevents disease, yet the underlying molecular mechanisms throughout a whole organism are incompletely understood. Here, Molecular Transducers of Physical Activity Consortium (MoTrPAC) profiled temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome, immunome in blood, plasma, 18 solid tissues Rattus norvegicus over 8 weeks endurance training. The resulting data compendium...
Abstract Transcription factors (TFs) play a key role in regulating gene expression and responses to stimuli. We conducted an integrated analysis of chromatin accessibility, DNA methylation, RNA across eight rat tissues following endurance exercise training (EET) map epigenomic changes transcriptional determine TFs involved. uncovered tissue-specific TF motif enrichment all omic layers, differentially accessible regions (DARs), methylated (DMRs), expressed genes (DEGs). discovered distinct...
Immediate-early response genes (IEGs) are rapidly and transiently induced following an extracellular signal. Elucidating the IEG patterns in single cells (SCs) requires assaying large numbers of timed samples at high accuracy while minimizing handling effects. To achieve this, we developed validated RNA stabilization Buffer for Examination Single-cell Transcriptomes (RNA-Best), a versatile single-step cell tissue preservation protocol that stabilizes intact SCs without perturbing...
Background: Marine recruits training at Parris Island experienced an unexpectedly high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite preventive measures including a supervised, 2-week, pre-entry quarantine. We characterize SARS-CoV-2 transmission in this cohort. Methods: Between May and November 2020, we monitored 2,469 unvaccinated, mostly male, prospectively during basic training. If participants tested negative for by quantitative polymerase chain...
Abstract Biochemical correlates of stochastic single-cell fates have been elusive, even for the well-studied mammalian cell cycle. We monitored dynamics ERK and Akt pathways, critical cycle progression hubs anti-cancer drug targets, paired them to division events in same single cells using non-transformed MCF10A epithelial line. Following growth factor treatment, that divide both activities are significantly higher within S-G2 time window (~ 8.5–40 h). Such differences were much smaller...
ABSTRACT The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response infection and complex immunological insight that are only possible with preclinical studies. Hamsters model reliably exhibit more SARS-CoV-2 disease similar hospitalized patients, making them pertinent for evaluation. We demonstrate prime or prime-boost...
Abstract Networks underlie much of biology from subcellular to ecological scales. Yet, understanding what experimental data are needed and how use them for unambiguously identifying the structure even small networks remains a broad challenge. Here, we integrate dynamic least squares framework into established modular response analysis (DL-MRA), that specifies sufficient perturbation time course robustly infer arbitrary two three node networks. DL-MRA considers important network properties...
The environment of a living cell is vastly different from that an in vitro reaction system, issue presents great challenges to the use models, or computer simulations based on them, for understanding biochemistry vivo. Virus capsids make excellent model system such questions because they typically have few distinct components, making them amenable and modeling studies, yet their assembly can involve complex networks possible reactions cannot be resolved detail by any current experimental...
A main application for mRNA sequencing (mRNAseq) is determining lists of differentially-expressed genes (DEGs) between two or more conditions. Several software packages exist to produce DEGs from mRNAseq data, but they typically yield different DEGs, sometimes markedly so. The underlying probability model used describe data central deriving and not surprisingly most softwares use models assumptions analyze data. Here, we propose a mechanistic justification as binomial process, with technical...
Endurance exercise is an important health modifier. We studied cell-type specific adaptations of human skeletal muscle to acute endurance using single-nucleus (sn) multiome sequencing in vastus lateralis samples collected before and 3.5 hours after 40 min at 70% VO