A5088758848- Muscle Physiology and Disorders
- Nerve injury and regeneration
- Exercise and Physiological Responses
- Mesenchymal stem cell research
- Nutrition and Health in Aging
- Tissue Engineering and Regenerative Medicine
- Adipose Tissue and Metabolism
- Signaling Pathways in Disease
- Childhood Cancer Survivors' Quality of Life
- Muscle activation and electromyography studies
- Planarian Biology and Electrostimulation
- RNA Research and Splicing
- Muscle metabolism and nutrition
- Telomeres, Telomerase, and Senescence
- Genetics, Aging, and Longevity in Model Organisms
- GDF15 and Related Biomarkers
- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Extracellular vesicles in disease
- Effects of Radiation Exposure
- Pluripotent Stem Cells Research
- Fibroblast Growth Factor Research
- Cancer survivorship and care
- Frailty in Older Adults
Duke University
2022-2024
University of Rochester
2020-2024
University of Rochester Medical Center
2015-2023
Regenerative Medicine Institute
2015-2021
Cancer Institute (WIA)
2021
Roswell Park Comprehensive Cancer Center
2016
Cancer Genetics (United States)
2016
Harvard University
2010-2014
Massachusetts General Hospital
2012-2014
Ottawa Hospital
2003-2007
Neuromuscular junction degeneration is a prominent aspect of sarcopenia, the age-associated loss skeletal muscle integrity. Previously, we showed that stem cells activate and contribute to mouse neuromuscular regeneration in response denervation (Liu et al., 2015). Here, examined gene expression profiles integrity aged muscles, unexpectedly found limited despite high level degenerated junctions. Instead, junctions were associated with reduced contribution from cells. Indeed, cell depletion...
Across different niches, subsets of highly functional stem cells are maintained in a relatively dormant rather than proliferative state. Our understanding dynamics tissue-specific during conditions increased tissue turnover remains limited. Using TetO-H2B-GFP reporter history, we identify skeletal muscle cell, or satellite cells, that retain (LRC) lose (nonLRC) the H2B-GFP label. We show mice LRCs and nonLRCs formed at birth persist postnatal growth adult repair. Functionally, born...
Skeletal muscle maintenance depends on motor innervation at neuromuscular junctions (NMJs). Multiple mechanisms contribute to NMJ repair and maintenance; however stem cells (satellite cells, SCs), are deemed have little impact these processes. Therefore, the applicability of SC studies attenuate loss due deterioration as observed in diseases aging is ambiguous. We employed mice with an inducible Cre, conditionally expressed DTA deplete or GFP track SCs. found depletion exacerbated atrophy...
ABSTRACT The functional role of Pax7-expressing satellite cells (SCs) in postnatal skeletal muscle development beyond weaning remains obscure. Therefore, the relevance SCs during prepubertal growth, a period after but prior to onset puberty, has not been examined. Here, we have characterized mouse growth prepuberty and found significant increases myofiber cross-sectional area that correlated with SC-derived myonuclear number. Remarkably, genome-wide RNA-sequencing analysis established...
Mesenchymal progenitors of the lateral plate mesoderm give rise to various cell fates within limbs, including a heterogeneous group muscle-resident mesenchymal cells. Often described as fibro-adipogenic progenitors, these cells are key players in muscle development, disease, and regeneration. To further define this population(s), we perform lineage/reporter analysis, flow cytometry, single-cell RNA sequencing, immunofluorescent staining, differentiation assays on normal injured murine...
Utrophin has been studied extensively in recent years an effort to find a cure for Duchenne muscular dystrophy. In this context, we previously showed that mice expressing enhanced muscle calcineurin activity (CnA*) displayed elevated levels of utrophin around their sarcolemma. the present study, therefore crossed CnA* with mdx determine suitability elevating preventing dystrophic pathology. Muscles from mdx/CnA* increased nuclear localization NFATc1 and fiber type shift towards slower...
Mammalian limb and trunk skeletal muscles are composed of muscle fibers that differ in contractile molecular properties. They commonly divided into four categories according to the myosin heavy chain they express: I, IIA, IIX IIB, ranging from slowest fastest. Individual motor axons innervate tens fibers, nearly all which same type. The mechanisms accounting for this striking specificity, termed unit homogeneity, remain incompletely understood, part because there have been no markers...
A therapeutic strategy to treat Duchenne muscular dystrophy (DMD) involves identifying compounds that can elevate utrophin expression in muscle fibers of affected patients. The dystrophin homologue functionally substitute for when its levels are enhanced the mdx mouse model DMD. Utrophin skeletal is regulated by mechanisms promote slow myofiber program. Since activation peroxisome proliferator-activated receptor (PPAR) beta/delta promotes oxidative phenotype muscle, we initiated studies...
Abstract Muscle regeneration depends on a robust albeit transient inflammatory response. Persistent inflammation is feature of age-related regenerative deficits, yet the underlying mechanisms are poorly understood. Here, we find inflammatory-related CC-chemokine-receptor 2 (Ccr2) expression in non-hematopoietic myogenic progenitors (MPs) during regeneration. After injury, Ccr2 MPs corresponds to levels its ligands, chemokines Ccl2, 7, and 8. We stimulation Ccr2-activity inhibits MP fusion...
Utrophin levels have recently been shown to be more abundant in slow vs. fast muscles, but the nature of molecular events underlying this difference remains fully elucidated. Here, we determined whether is due expression utrophin A or B, and examined transcriptional regulatory mechanisms are also involved. Immunofluorescence experiments revealed that slower fibers contain significantly extrasynaptic regions as compared with fibers. Single-fiber RT-PCR analysis demonstrated transcripts...
Duchenne muscular dystrophy (DMD) is a progressive and ultimately fatal skeletal muscle disease. Currently, the most effective therapy administration of subclass glucocorticoids, notably deflazacort. Although deflazacort treatment can attenuate DMD progression, extend ambulation, maintain strength, mechanism its action remains unknown. Prior observations have shown that activation JNK1-mediated signal transduction cascade contributes to progression phenotype, in part by phosphorylation...
During aging, muscle mass decreases, leading to sarcopenia, associated with low-level chronic inflammation (inflammaging), which induces sarcopenia by promoting proteolysis of fibers and inhibiting their regeneration. Patients a variety pathologic conditions including rheumatoid arthritis (RA), have systemically elevated TNFα serum levels, transgenic mice overexpression (TNF-Tg mice, model RA) develop between adolescence adulthood before they age. However, if how contributes the pathogenesis...
In addition to showing differences in the levels of contractile proteins and metabolic enzymes, fast slow muscles also differ their expression profile structural synaptic proteins. Because utrophin is a protein expressed at neuromuscular junction, we hypothesize that its may be different between muscles. Western blots showed that, compared with extensor digitorum longus (EDL) muscles, soleus contain significantly more utrophin. Quantitative RT-PCR revealed this difference accompanied by...
We examined whether calcineurin-NFAT (nuclear factors of activated T cells) signaling plays a role in specifically directing the expression utrophin synaptic compartment muscle fibers. Immunofluorescence experiments revealed accumulation components cascade within postsynaptic membrane domain neuromuscular junction. RT-PCR analysis using vs. extrasynaptic regions fibers confirmed these findings by showing an calcineurin transcripts compartment. also effect on gene expression. Pharmacological...
We recently demonstrated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel blocker, in enhancing remyelination and recovery nerve conduction velocity motor function after sciatic crush injury mice. Although muscle atrophy occurs very rapidly injury, effect 4-AP on intrinsic contractile is largely unknown.Mice were assigned to no-injury groups followed for 3, 7, 14 days with/without or saline treatment. Morphological, functional, transcriptional properties skeletal...
In this study, we crossbred mdx mice with transgenic expressing a small peptide inhibitor for calmodulin (CaM), known as the CaM-binding protein (CaMBP), driven by slow fiber-specific troponin I promoter. This strategy allowed us to determine impact of interfering Ca2+/CaM-based signaling in dystrophin-deficient myofibers. Consistent impairments Ca2+/CaM-regulated enzymes calcineurin and Ca2+/CaM-dependent kinase, nuclear accumulation factor activated T-cell c1 myocyte enhancer 2C was...
Skeletal muscle regenerative potential declines with age, in part due to deficiencies resident stem cells (satellite cells, SCs) and derived myogenic progenitors (MPs); however, the factors responsible for this decline remain obscure. TGFβ superfamily signaling is an inhibitor of differentiation, elevated activity aged skeletal muscle. Surprisingly, we find reduced expression Smad4, downstream cofactor canonical signaling, target Id1 SCs MPs during regeneration. Specific deletion Smad4 adult...
Objective To examine and quantify the sexual dimorphism in pathologic features manifested musculoskeletal cardiopulmonary systems incidence of mortality tumor necrosis factor–transgenic ( TNF ‐Tg; Tg3647 strain) mouse model inflammatory erosive arthritis. Methods Kaplan‐Meier survival estimates were determined male female mice sex‐matched wild‐type WT ) littermate mice. Longitudinal cross‐sectional outcomes assessed via ultrasound, micro–computed tomography, grip strength measurements,...
During prepubertal development, muscle stem cells (satellite cells, SCs) actively contribute to myofiber growth. Because some SCs are active during this time, they may be particularly susceptible damage. Using a Small Animal Radiation Research Platform (SARRP), we investigated the effects of local fractionated radiation treatment on SCs. Immediately after regimen, there was reduction in SC number. Although surviving had deficiencies function, myogenic potential remained. Indeed, regenerative...