A5044450315- DNA Repair Mechanisms
- Pluripotent Stem Cells Research
- Muscle Physiology and Disorders
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- Tissue Engineering and Regenerative Medicine
- Nuclear Structure and Function
- Renal and related cancers
- Mesenchymal stem cell research
- Health Systems, Economic Evaluations, Quality of Life
- Viral Infections and Immunology Research
- Spaceflight effects on biology
- RNA Research and Splicing
- Cellular Mechanics and Interactions
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Planarian Biology and Electrostimulation
- Neurogenetic and Muscular Disorders Research
- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- Heat shock proteins research
- Pharmaceutical Economics and Policy
- Virus-based gene therapy research
Children's Hospital of Philadelphia
2025
University of Pennsylvania
2016-2023
University of Connecticut
2017
University of Cincinnati Medical Center
2006-2013
University of Cincinnati
2006-2011
Sabin Vaccine Institute
2010-2011
Muscle stem cells (MuSCs) are essential for tissue homeostasis and regeneration, but the potential contribution of MuSC morphology to in vivo function remains unknown. Here, we demonstrate that quiescent MuSCs morphologically heterogeneous exhibit different patterns cellular protrusions. We classified into three functionally distinct cell states: responsive, intermediate, sensory. shift between states promotes regeneration is regulated by sensing protein Piezo1. Pharmacological activation...
Embryonic stem (ES) cells give rise to all cell types of an organism. Since mutations at this embryonic stage would affect and be detrimental the overall health organism, robust mechanisms must exist ensure that genomic integrity is maintained. To test proposition, we compared capacity murine ES repair DNA double-strand breaks with differentiated cells. Of 2 major pathways breaks, error-prone nonhomologous end joining (NHEJ) predominated in mouse fibroblasts, whereas high fidelity homologous...
Background Telomere defects are thought to play a role in cardiomyopathies, but the specific cell type affected by disease human hearts is not yet identified. The aim of this study was systematically evaluate specificity telomere shortening patients with heart failure relation their cardiac disease, age, and sex. Methods Results We studied tissues from utilizing quantitative fluorescence situ hybridization, highly sensitive method single‐cell resolution. In study, total 63 left ventricular...
The human DEK gene is frequently overexpressed and sometimes amplified in cancer. Consistent with oncogenic functions, Dek knockout mice are partially resistant to chemically induced papilloma formation. Additionally, knockdown vitro sensitizes cancer cells DNA damaging agents induces cell death via p53-dependent -independent mechanisms. Here we report that important for double-strand break repair. depletion lines xenografts was sufficient induce a damage response as assessed by detection of...
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease in which extraskeletal (heterotopic) bone forms within tissues such as skeletal muscles, often response to injury. Mutations the BMP type I receptor ACVR1/ALK2 cause FOP by increasing pathway signaling. In contrast growing understanding of inappropriate formation tissue muscle FOP, much still unknown about regenerative capacity adult diseased muscles. Utilizing an inducible ACVR1R206H knock-in mouse, we found that injured...
Resident macrophages exist in a variety of tissues, including tendon, and play context-specific roles their tissue residence. In this study, we define the spatiotemporal distribution phenotypic profile tendon resident crosstalk with neighboring fibroblasts extracellular matrix (ECM) during murine development, growth, homeostasis. Fluorescent imaging cryosections revealed that F4/80+ reside adjacent to Col1a1-CFP+ Scx-GFP+ within fascicle from embryonic development (E15.5) into adulthood...
Beckwith-Wiedemann Syndrome (BWS) is an epigenetic overgrowth syndrome caused by methylation changes in the human 11p15 chromosomal locus. Patients with BWS may exhibit hepatomegaly, as well increased risk of hepatoblastoma. To understand impact these liver, we performed a multiomic study [single nucleus RNA-sequencing (snRNA-seq) + single assay for transposable-accessible chromatin-sequencing (snATAC-seq)] both BWS-liver and nonBWS-liver tumor-adjacent tissue. Our approach uncovers...
Muscle stem cells (MuSCs) contribute to muscle regeneration following injury. In many disorders, the repeated cycles of damage and repair lead cell dysfunction. While telomere attrition may aberrant functions, methods accurately measure length in from skeletal muscles have not been demonstrated. Here, we optimized validated such a method, named MuQ-FISH, for analyzing MuSCs either mice or humans. Our analysis showed no differences between young aged uninjured wild-type mice, but isolated...
Skeletal muscle has remarkable regenerative ability after injury. Mesenchymal fibro-adipogenic progenitors (FAPs) are necessary, active participants during this repair process, but the molecular signatures of these cells and their functional relevance remain largely unexplored. Here, using a lineage tracing mouse model (Gli1-CreER Tomato), we demonstrate that Gli1 marks small subset muscle-resident FAPs with elevated Hedgehog (Hh) signaling. Upon notexin injury, preferentially rapidly...
During the repeated cycles of damage and repair in many muscle disorders, including Duchenne muscular dystrophy (DMD), stem cell (MuSC) pool becomes less efficient at responding to repairing damage. The underlying mechanism such dysfunction is not fully known. Here, we demonstrate that distinct early telomere shortening diseased MuSCs both mice young DMD patients associated with aberrant NF-κB activation. We find prolonged activation chronic injuries leads shortened telomeres Ku80...
Pax7 is a transcription factor involved in the specification and maintenance of muscle stem cells (MuSCs). Upon injury, MuSCs leave their quiescent state, downregulate differentiate, contributing to skeletal regeneration. In majority regeneration studies, are isolated by fluorescence-activated sorting (FACS), based on cell surface markers. It known that heterogeneous population only small percentage true able self-renew. A strong reporter line would be valuable study vivo behavior...
Abstract Astronauts are exposed to harsh conditions, including cosmic radiation and microgravity. Spaceflight elongates human telomeres in peripheral blood, which shorten upon return Earth approach baseline levels during postflight recovery. also encounter muscle atrophy, losing up 20% loss of mass on spaceflights. Telomere length changes cells astronauts remain unexplored. This study investigates telomere alterations grounded mice experiencing exposure via a hindlimb unloading spaceflight...
The mdx4cv mouse is a common model to study Duchenne muscular dystrophy. most used methodology identify the genotype of these mice Sanger DNA sequencing.Here, we provide simple, cost-effective alternative approach wild-type, heterozygous, or homozygous/hemizygous genotypes mice, using commonly available laboratory equipment and reagents.Our technique exploits restriction fragment length polymorphism that generated by point mutation found in exon 53 mice.This can benefit laboratories require...
Summary Whether cell forces or extracellular matrix (ECM) can impact genome integrity is largely unclear. Here, acute perturbations (~1hr) to actomyosin stress ECM elasticity cause rapid and reversible changes in lamin-A, DNA damage, cycle. Embryonic hearts, differentiated iPS-cells, various nonmuscle types all show that actomyosin-driven nuclear rupture causes cytoplasmic mis-localization of repair factors excess damage. Binucleation micronuclei increase as telomeres shorten, which favor...