A5082313949- Genomics and Chromatin Dynamics
- Cell Image Analysis Techniques
- Cellular Mechanics and Interactions
- T-cell and B-cell Immunology
- Gene expression and cancer classification
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Cytomegalovirus and herpesvirus research
- Image Processing Techniques and Applications
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- Advanced X-ray Imaging Techniques
- AI in cancer detection
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Gene Regulatory Network Analysis
- Microtubule and mitosis dynamics
- Spectroscopy Techniques in Biomedical and Chemical Research
- Healthcare Technology and Patient Monitoring
- Hearing, Cochlea, Tinnitus, Genetics
- Advanced biosensing and bioanalysis techniques
- Genetic Mapping and Diversity in Plants and Animals
- Chromosomal and Genetic Variations
University of Michigan–Ann Arbor
1998-2024
Ann Arbor Center for Independent Living
2015
Carnegie Mellon University
2002
Pittsburgh Supercomputing Center
2002
Extensive simulations of PAMAM dendrimer generation 2 were performed at several pH conditions with explicit water molecules, to obtain proper and validity for additional without water. Within the range validity, simulation greatly extends size duration practical simulations. We investigated effects long-range interaction parameters such as distance dielectric constant molecular dynamics water, concluding that charged distance-dependent but cutoff best mimics results. Structural variations...
Significance We explored the human genome as a dynamical system. Using data-guided mathematical framework and genome-wide assays, we interrogated relationship between architecture (structure) gene expression (function) its impact on phenotype, which defines 4D Nucleome. Structure function entrained with remarkable persistence in genes that underlie wound healing processes circadian rhythms. intragene intergene contact maps, identified networks high potential for coregulation colocalization,...
Chronic stress and elevated glucocorticoid hormone are associated with decreases in the intestinal epithelial tight junction protein claudin-1 (CLDN1). Human/rat CLDN1 promoters contain response elements (GREs) adjacent transcription repressor HES1 binding N-boxes. Notch signaling target expression was high receptor (NR3C1) low at crypt base pattern reversed apex. reduced overall rat colon NR3C1 that downregulation. Chromatin-immunoprecipitation experiments showed bind to promoter crypts....
Abstract Chromatin architecture, a key regulator of gene expression, can be inferred using chromatin contact data from chromosome conformation capture, or Hi-C. However, classical Hi-C does not preserve multi-way contacts. Here we use long sequencing reads to map genome-wide contacts and investigate higher order organization in the human genome. We hypergraph theory for representation analysis, quantify structures neonatal fibroblasts, biopsied adult B lymphocytes. By integrating with...
Abstract Quantitative analysis of morphological changes in a cell nucleus is important for the understanding nuclear architecture and its relationship with pathological conditions such as cancer. However, dimensionality imaging data, together great variability shapes, presents challenges 3D analysis. Thus, there compelling need robust morphometric techniques to carry out population-wide We propose new approach that combines modeling, analysis, interpretation characteristics nuclei nucleoli...
Cell deformation is regulated by complex underlying biological mechanisms associated with spatial and temporal morphological changes in the nucleus that are related to cell differentiation, development, proliferation, disease. Thus, quantitative analysis of size shape nuclear structures 3D microscopic images important not only for investigating organization, but also detecting treating pathological conditions such as cancer. While many efforts have been made develop characteristics 2D or...
The actin cytoskeleton of rabbit proximal tubules was assessed by deoxyribonuclease (DNase) binding, sedimentability detergent-insoluble actin, laser-scanning confocal microscopy, and ultrastructure during exposure to hypoxia, antimycin, or antimycin plus ionomycin. One-third total DNase reactive in control cells prior deliberate depolymerization, a similar proportion unsedimentable from detergent lysates 2.5 h at 100,000 g. Tubules injured hypoxia alone, without glycine, showed...
Morphology of the cell nucleus has been used as a key indicator disease state and prognosis, but typically without quantitative rigor. It is also not well understood how nuclear morphology varies with time across different genetic backgrounds in healthy cells. To help answer these questions we measured size shape nuclei cell-cycle-synchronized primary human fibroblasts from 6 individuals at 32 points over 75 hour period.The was modeled an ellipsoid its dynamics analyzed. Shape volume changed...
Histone deacetylase inhibitors, such as valproic acid (VPA), have important clinical therapeutic and cellular reprogramming applications. They induce chromatin reorganization that is associated with altered morphology. However, there a lack of comprehensive characterization VPA-induced changes nuclear size shape. Here, we quantify 3D morphology primary human astrocyte cells treated VPA over time (hence, 4D). We compared volumetric surface-based representations identified seven features...
The waltzing guinea pig displays severe inner ear dysfunction that involves both an auditory and a vestibular manifestation. aim of this study was to characterize pathological tail-like extension the hair cells, cytocaud. Our data suggest nearly all type I cells in have cytocauds, which appear as membrane-bound tails containing mitochondria cytoplasm proceed basal direction toward basement membrane. extensions either attach membrane or penetrate it, further into extracellular matrix. A core...
Abstract Quantitative analysis of morphological changes in a cell nucleus is important for the understanding nuclear architecture and its relationship with pathological conditions such as cancer. However, dimensionality imaging data, together great variability shapes, presents challenges 3D analysis. Thus, there compelling need robust morphometric techniques to carry out population-wide We propose new approach that combines modeling, analysis, interpretation characteristics nuclei nucleoli...
SUMMARY Genome architecture is important in transcriptional regulation and study of its features a critical part fully understanding cell identity. Altering identity possible through overexpression transcription factors (TFs); for example, fibroblasts can be reprogrammed into muscle cells by introducing MYOD1. How TFs dynamically orchestrate genome as adopts new during reprogramming not well understood. Here we show that MYOD1-mediated human the myogenic lineage undergoes transition, which...
Abstract Cell deformation is regulated by complex underlying biological mechanisms associated with spatial and temporal morphological changes in the nucleus that are related to cell differentiation, development, proliferation, disease. Thus, quantitative analysis of size shape nuclear structures 3D microscopic images important not only for investigating organization, but also detecting treating pathological conditions such as cancer. While many efforts have been made develop characteristics...
Abstract Colon crypts are recognized as a mechanical and biochemical Turing patterning model. epithelial Caco‐2 cell monolayer demonstrated 2D patterns via force analysis of apical tight junction live imaging which illuminated actomyosin meshwork linking the network individual cells. Actomyosin forces act in mechanobiological manner that alters cell/nucleus/tissue morphology. We observed rotational motion nucleus cells appears to be driven by during formation differentiated confluent...
Abstract Recent reports suggest that actomyosin meshwork act in a mechanobiological manner alter cell/nucleus/tissue morphology, including human colon epithelial Caco-2 cancer cells form polarized 2D epithelium or 3D sphere/tube when placed different culture conditions. We observed the rotational motion of nucleus vitro appears to be driven by network prior formation differentiated confluent epithelium. cell monolayer preparations demonstrated patterns consistent with Allan Turing’s “gene...
Abstract Direct reprogramming of human fibroblasts into hematopoietic stem cells (HSCs) shows promise for generating autologous treatment blood and immune-related diseases. However, low conversion efficiency existing protocols points to gaps in our understanding opportunities identification optimal transcription factor (TF) combinations, which is a major bottleneck HSC generation. In this study, we tested novel algorithmically-predicted TF recipe (GATA2, GFIB1, FOS, REL, STAT5A) inducing...
The advent of advanced robotic platforms and workflow automation tools has revolutionized the landscape biological research, offering unprecedented levels precision, reproducibility, versatility in experimental design. In this work, we present an automated modular for exploring cell behavior two-dimensional culture systems. By integrating BioAssemblyBot® (BAB) platform BioApps™ automater with live-cell fluorescence microscopy, our facilitates execution analysis vitro migration proliferation...
Abstract Restoring the epidermal barrier after injury requires spatial and temporal orchestration of migration, proliferation, signaling across many cell types. The mechanisms that coordinate this complex process are incompletely understood. In vitro wound assays common model systems for examining these in healing. scratch assay, a cell-free gap is created by mechanical removal cells from monolayer, followed monitoring migration into over time. While simple low-cost, manual limited low...
Abstract Histone deacetylase inhibitors, such as valproic acid (VPA), have important clinical therapeutic and cellular reprogramming applications. They induce chromatin re-organization that is associated with altered morphology. However, there a lack of comprehensive characterization VPA-induced changes nuclear size shape. Here, we quantify 3D morphology primary human astrocyte cells treated VPA over time (hence, 4D). We compared volumetric surface-based representations identified seven...