A5036836747- Liver physiology and pathology
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Pancreatic function and diabetes
- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Tissue Engineering and Regenerative Medicine
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Additive Manufacturing and 3D Printing Technologies
- Birth, Development, and Health
- Mathematical Biology Tumor Growth
- Cell Image Analysis Techniques
- Microtubule and mitosis dynamics
- Aerosol Filtration and Electrostatic Precipitation
- Carbon Nanotubes in Composites
- Polyamine Metabolism and Applications
- RNA Research and Splicing
- Pediatric Hepatobiliary Diseases and Treatments
- Neuroscience and Neuropharmacology Research
University of North Carolina Health Care
2021
National Institutes of Health
2018-2021
National Institute of Environmental Health Sciences
2016-2020
Research Triangle Park Foundation
2016
Duke University Hospital
2015
Duke Medical Center
2015
Orthopaedic Research Laboratories
2015
University of North Carolina at Chapel Hill
2011-2012
North Carolina State University
2011
UNC Lineberger Comprehensive Cancer Center
2011
Mitochondrial function affects many aspects of cellular physiology, and, most recently, its role in epigenetics has been reported. Mechanistically, how mitochondrial alters DNA methylation patterns the nucleus remains ill defined. Using a cell culture model induced (mtDNA) depletion, this study we show that progressive dysfunction leads to an early transcriptional and metabolic program centered on metabolism various amino acids, including those involved methionine cycle. We find also...
Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but compromised by inefficient engraftment, cell dispersal ectopic sites, and emboli formation. Grafting strategies have been devised of human hepatic stem cells (hHpSCs) embedded into a mix soluble signals extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in niches. The hHpSCs maintain stable phenotype under the graft conditions. grafts were transplanted livers...
The impact of mitochondrial dysfunction in epigenetics is emerging, but our understanding this relationship and its effect on gene expression remains incomplete. We previously showed that acute DNA (mtDNA) loss leads to histone hypoacetylation. It be defined if these changes are maintained when chronic they alter expression. To fill gaps knowledge, we here studied a progressive model mtDNA depletion using biochemical, pharmacological, genomics, genetic assays. show histones primarily...
Tobacco smoke exposure contributes to the global burden of communicable and chronic diseases. To identify immune cells affected by smoking, we use single-cell RNA sequencing on peripheral blood from smokers nonsmokers. Transcriptomes reveal a subpopulation FCGR3A (CD16)-expressing Natural Killer (NK)-like CD8 T lymphocytes that increase in smokers. Mass cytometry confirms elevated CD16+ Inferred as highly differentiated pseudotime analysis, NK-like express markers characteristic effector...
Mitochondrial-driven alterations of the epigenome have been reported, but whether they are relevant at organismal level remains unknown. The viable yellow agouti mouse (Avy) is a powerful epigenetic biosensor model that reports on DNA methylation status Avy locus, which established prior to three-germ-layer separation, through coat color animals. Here we show maternal exposure rotenone, potent mitochondrial complex I inhibitor, not only changes locus in skin broadly affects liver methylome...
Abstract The ability of cells to proliferate, differentiate, transduce extracellular signals and assemble tissues involves structural connections between nucleus cytoskeleton. Yet, how the mechanics these vary inside stem is not fully understood. To address those questions, we combined two-dimensional particle-tracking microrheology morphological measures using variable reduction techniques measure whether cytoplasmic allow for discrimination different human adherent cell types across...
Epithelial organs are almost universally secretory. The lung secretes mucus of extremely variable consistency. In the early prenatal period, secretions largely unknown composition, consistency, and flow rates. addition to net outflow from secretion, embryonic exhibits transient reversing flows peristalsis. Airway peristalsis (AP) begins as soon smooth muscle forms, persists until birth. Since is liquid-filled, action can transport fluid far immediately adjacent tissues. sensation internal...
Summary Maintenance of the mitochondrial inner membrane potential (ΔΨM) is critical for many aspects function, including protein import and ion homeostasis. While ΔΨM loss its consequences are well studied, little known about effects increased ΔΨM. In this study, we used cells deleted ATPIF1 , a natural inhibitor hydrolytic activity ATP synthase, as genetic model hyperpolarization. Our data show that chronic increase leads to nuclear DNA hypermethylation, regulating transcription...
To life scientists, one important feature offered by RNAseq, a next-generation sequencing tool used to estimate changes in gene expression levels, lies its unprecedented resolution. It can score countable differences transcript numbers among thousands of genes and between experimental groups, all at once. However, high cost limits designs very small sample sizes, usually N = 3, which often results statistically underpowered analysis poor reproducibility. All these issues are compounded the...
Tobacco smoke exposure impacts immune response, leukocyte subtypes, DNA methylation, and gene expression. We performed single-cell RNA sequencing (scRNAseq) on >45,000 human peripheral blood cells from smokers nonsmokers. Transcriptomes revealed a subpopulation of FCGR3A (CD16)-expressing Natural Killer (NK)-like T lymphocytes that increased in smokers. Mass cytometry confirmed an increase the frequency CD16+ CD8 The majority were CD45RA positive, indicating effector memory re-expressing...
PGC1α is a transcriptional coactivator in peripheral tissues, but its function the brain remains poorly understood. Various brain-specific Pgc1α isoforms have been reported mice and humans, including two fusion transcripts (FTs) with non-coding repetitive sequences, their unknown. The FTs initiate at simple sequence repeat locus ∼570 Kb upstream from reference promoter; one also includes portion of short interspersed nuclear element (SINE). Using publicly available genomics data, here we...
Nanostructured materials and exploiting their properties in stereolithography (SL) may open new markets for unique rapidly manufactured functional devices. Controlled amounts of multiwalled carbon nanotubes (MWCNTs) were successfully dispersed SL epoxy-based resins complex three-dimensional (3D) parts fabricated by means a multi-material setup. The effect the nanosized filler was evaluated using mechanical testing. Small dispersions MWCNTs resulted significant effects on physical polymerized...
Abstract The impact of mitochondria in epigenetics is emerging but our understanding this relationship and its on gene expression remain incomplete. We previously showed that acute mitochondrial DNA (mtDNA) loss leads to histone hypoacetylation. It remains be defined if these changes are maintained when dysfunction chronic and, importantly, they sufficient alter expression. To fill gaps, we here studied both a progressive model mtDNA depletion using biochemical, pharmacological, genomics...
Abstract The peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1α) is known as a transcriptional in peripheral tissues but its function the brain remains poorly understood. Various brain-specific Pgc1α isoforms have been reported mice and humans, including transcripts derived from novel promoter about ∼580 Kb upstream reference gene. These incorporate repetitive sequences simple sequence repeat (SSR) short interspersed nuclear element (SINE) classes are predicted to...
Single-cell RNA sequencing (scRNA-seq) technologies have precipitated the development of bioinformatic tools to reconstruct cell lineage specification and differentiation processes with single-cell precision. However, current start-up costs recommended data volumes for statistical analysis remain prohibitively expensive, preventing scRNA-seq from becoming mainstream. Here, we introduce amalgamation by latent semantic (SALSA), a versatile workflow that combines measurement reliability metrics...
Abstract Single-cell RNA sequencing (scRNA-seq) technologies have precipitated the development of bioinformatic tools to reconstruct cell lineage specification and differentiation processes with single-cell precision. However, start-up costs data volumes currently required for statistically reproducible insight remain prohibitively expensive, preventing scRNA-seq from becoming mainstream. Here, we introduce amalgamation by latent semantic analysis (SALSA), a versatile workflow address those...
Abstract Mitochondrial-driven alterations of the epigenome have been reported but whether they are relevant at organismal level remain unknown. The viable yellow agouti mouse ( A vy ) is a powerful epigenetic biosensor model that reports on DNA methylation status locus through coat color animals. Here we show maternal exposure to rotenone, potent mitochondrial complex I inhibitor, changes and broadly affects liver methylome offspring. These effects were accompanied by altered gene expression...
SUMMARY Tobacco smoke exposure has been found to impact immune response, leukocyte subtypes, DNA methylation, and gene expression in human whole blood. Analysis with single cell technologies will resolve smoking associated (sub)population compositions, differences, identification of rare subtypes masked by bulk fraction data. To characterize smoking-related changes primary cells, we performed single-cell RNA sequencing (scRNAseq) on >45,000 peripheral blood mononuclear cells (PBMCs) from...