A5013000327- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Mesenchymal stem cell research
- Exercise and Physiological Responses
- Cancer Research and Treatments
- Fatty Acid Research and Health
- Extracellular vesicles in disease
- Medical Imaging Techniques and Applications
- RNA Research and Splicing
- Muscle metabolism and nutrition
- Genomics and Chromatin Dynamics
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Bone Tissue Engineering Materials
- Spaceflight effects on biology
- Wound Healing and Treatments
- Long-Term Effects of COVID-19
- Biomedical and Engineering Education
- Interdisciplinary Research and Collaboration
- Nerve injury and regeneration
- Nuclear Structure and Function
- Cell Adhesion Molecules Research
University of Michigan
2018-2025
BioSurfaces (United States)
2018-2023
Boehringer Ingelheim (United States)
2021
Australian Regenerative Medicine Institute
2018
Monash University
2018
The Wallace H. Coulter Department of Biomedical Engineering
2017
Georgia Institute of Technology
2017
Abstract Skeletal muscle possesses a remarkable capacity to regenerate when injured, but confronted with major traumatic injury resulting in volumetric loss (VML), the regenerative process consistently fails. The of tissue and function from VML has prompted development suite therapeutic approaches these strategies have proceeded without comprehensive understanding molecular landscape that drives response. Herein, we administered an established rodent model monitored evolution healing...
Volumetric muscle loss (VML) overwhelms the innate regenerative capacity of mammalian skeletal (SkM), leading to numerous disabilities and reduced quality life. Immune cells are critical responders injury guide tissue resident stem cell– progenitor-mediated myogenic repair. However, how immune cell infiltration intercellular communication networks with altered following VML drive pathological outcomes remains underexplored. Herein, we contrast cellular molecular mechanisms injuries that...
Fibronectin (Fn) is an extracellular matrix protein that orchestrates complex cell adhesion and signaling through surface integrin receptors during tissue development, remodeling, disease, such as fibrosis. Fn sensitive to mechanical forces in its tandem type III repeats, resulting extensive molecular enlongation. As such, it has long been hypothesized cell- tissue-derived may activate "integrin switch" within the critical integrin-binding ninth 10th repeats—conferring differential...
During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility quality life. The repair regulated by tissue-resident stem cells called satellite (or [MuSCs]), but MuSCs decrease numbers regenerative capacity. transcriptional networks epigenetic changes confer diminished as result natural aging are only partially understood. Herein, we use an integrative genomics approach to profile from young aged animals before after injury. Integration these...
Specialized proresolving mediators (SPMs) actively limit inflammation and expedite its resolution by modulating leukocyte recruitment function. Here we profiled intramuscular lipid via liquid chromatography-tandem mass spectrometry–based metabolipidomics following myofiber injury investigated the potential role of SPMs in skeletal muscle repair. Both proinflammatory eicosanoids increased damage induced either injection barium chloride or synergist ablation–induced functional overload. Daily...
Volumetric muscle loss (VML) is an acute trauma that results in persistent inflammation, supplantation of tissue with fibrotic scarring, and decreased function. The cell types, nature cellular communication, locations drive the aberrant VML response have remained elusive. Herein, we used spatial transcriptomics on a mouse model observed engenders unique profibrotic pattern driven by crosstalk between inflammatory macrophages mesenchymal-derived cells. dysregulated impinged stem cell-mediated...
Abstract Specialized pro‐resolving mediators actively limit inflammation and support tissue regeneration, but their role in age‐related muscle dysfunction has not been explored. We profiled the mediator lipidome of aging via liquid chromatography‐tandem mass spectrometry tested whether treatment with resolvin D1 (RvD1) could rejuvenate regenerative ability aged muscle. Aged mice displayed chronic this was associated a basal deficiency 8‐oxo‐RvD1, E3, maresin 1, as well many anti‐inflammatory...
Adult stem cells decline in number and function old age identifying factors that can delay or revert age-associated adult cell dysfunction are vital for maintaining healthy lifespan. Here we show Vitamin A, a micronutrient is derived from diet metabolized into retinoic acid, acts as an antioxidant transcriptional regulator muscle cells. We first obstruction of dietary A young animals drives mitochondrial cycle mimics age. Next, pharmacologically targeted acid signaling myoblasts aged ex vivo...
Age-related skeletal muscle atrophy or sarcopenia is a significant societal problem that becoming amplified as the world's population continues to increase. The regeneration of damaged mediated by stem cells, but in old age cells become functionally attenuated. molecular mechanisms govern cell aging encompass changes across multiple regulatory layers and are integrated three-dimensional organization genome. To quantitatively understand how hierarchical chromatin architecture during aging, we...
During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume function impacting mobility quality life. Muscle often associated with denervation resident stem cells (satellite or MuSCs); however, the relationship between MuSCs innervation has not been established. Herein, we administered severe trauma to transgenic murine model that permits MuSC lineage tracing. We show subset specifically engraft in position proximal junction (NMJ), synapse myofibers motor...
The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle (VML), is a devastating type injury that results in exacerbated and persistent inflammation followed by fibrosis. mechanisms mediate the magnitude duration inflammatory response ensuing fibrosis after VML remain understudied, such, development regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators immune injury, varied with injuries heal...
Abstract During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume function in that impacts mobility quality life. Muscle often associated with denervation resident stem cells (satellite or MuSCs), but the relationship between MuSCs neural control has not been established. Herein, using combination single-cell transcriptomic analysis, high-resolution immunofluorescence imaging transgenic young aged mice as well from degeneration (Sod1 -/- ), compensatory...
ABSTRACT Volumetric muscle loss (VML) is an acute trauma that results in persistent inflammation, supplantation of tissue with fibrotic scarring, and decreased function. The cell types, nature cellular communication locations drive the aberrant VML response have remained elusive. Herein, we used spatial transcriptomics integrated single-cell RNA sequencing on mouse canine models administered VML. We observed engenders a unique pro-fibrotic pattern driven by crosstalk between macrophages...
Abstract Somatic cell fate is an outcome set by the activities of specific transcription factors and chromatin landscape maintained gene silencing alternate fates through physical interactions with nuclear scaffold. Here, we evaluate role scaffold as a guardian in human fibroblasts comparing effects transient loss (knockdown) mutation (progeria) functional Lamin A/C, core component We observed that A/C deficiency or disrupts morphology, heterochromatin levels, increases access to DNA...
Abstract The acute traumatic or surgical loss of skeletal muscle, known as volumetric muscle (VML), is a devastating type injury that results in exacerbated and persistent inflammation followed by fibrosis. mechanisms mediate the magnitude duration inflammatory response ensuing fibrosis after VML remain understudied such, development regenerative therapies has been limited. To address this need, we profiled how lipid mediators, which are potent regulators immune injury, varied with injuries...
Abstract Chronic inflammation and deregulated acute immune cell responses to injury contribute age-associated skeletal muscle dysfunction. Specialized pro-resolving mediators (SPMs) control support myofiber regeneration in young mice, but their role aging remains unknown. Here we examined the effect of age on mediator lipidome via LC-MS based lipidomic profiling tested whether systemic administration SPM resolvin D1 (RvD1) could limit excessive improve regenerative capacity aged muscle. Aged...
During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility quality life. The repair regulated by tissue resident stem cells called satellite (MuSCs), but MuSCs decrease numbers regenerative capacity. transcriptional networks epigenetic changes confer diminished as result natural aging are partially understood. Herein, an integrative genomics approach was utilized to profile from young aged animals before after injury. Integration these datasets...
ABSTRACT Volumetric muscle loss (VML) overwhelms the innate regenerative capacity of mammalian skeletal (SkM), leading to numerous disabilities and reduced quality life. Immune cells are critical responders injury guide tissue resident stem cell progenitor mediated myogenic repair. However, how immune infiltration inter-cellular communication networks with altered following VML drive pathological outcomes remains underexplored. Herein, we contrast cellular molecular mechanisms injuries that...