Young Charles JangEmory University | EU
Young Charles Jang
Ph.D.
About
108
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Introduction
Additional affiliations
September 2014 - present
November 2010 - July 2014
July 2004 - December 2008
Publications
Publications (108)
Severe tissue loss resulting from extremity trauma, such as volumetric muscle loss (VML), poses significant clinical challenges for both general and military populations. VML disrupts the endogenous tissue repair mechanisms, resulting in acute and unresolved chronic inflammation and immune cell presence, impaired muscle healing, scar tissue formati...
Volumetric muscle loss (VML) results in permanent functional deficits and remains a substantial regenerative medicine challenge. A coordinated immune response is crucial for timely myofiber regeneration, however the immune response following VML has yet to be fully characterized. Here, we leveraged dimensionality reduction and pseudo-time analysis...
Duchenne muscular dystrophy (DMD) causes patients to suffer from ambulatory disability and cardiorespiratory failure, the latter of which leads to premature death. Due to its role in respiration, the diaphragm is an important muscle for study. A common method for evaluating diaphragm function is ex vivo force testing, which only allows for an end p...
Skeletal muscle regeneration is an energy-demanding biological process that relies on mitochondria to generate ATP. While interfibrillar mitochondrial networks in healthy skeletal muscle fibers exhibit an organized architecture segregated into columns along the Z-line of the myofiber, regenerating fibers demonstrate altered mitochondrial networks t...
INTRODUCTION: Skeletal muscle homeostasis is maintained by resident stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, MuSC function is coordinated by the cellular and acellular components of their microenvironment, or niche. While the processes that couple neurotransmission and muscle contraction have been well c...
In this study, a reactive oxygen species (ROS)‐responsive hydrogel sensor (PD/MnO2 hydrogel) is developed that can efficiently detect senescent cells. Using immature murine articular chondrocytes with serial passages, the sensor can identify small interfering RNA (siRNA) knockdown of peroxisome proliferator‐activated receptor‐alpha (PPARα) based on...
Introduction:
Metabolic disorder promotes premature senescence and poses more severe cardiac dysfunction in females than males. While endurance exercise (EXE) has been known to confer cardioprotection against metabolic diseases, whether EXE-induced cardioprotection is associated with mitigating senescence in females remains unknown. Thus, the aim...
It is evident that both aged and diseased skeletal muscle exhibit interesting neuromuscular dynamics, characterized by changes in morphology and functionality of the synapse. Although they display a high regenerative capacity, skeletal muscles are still susceptible to nervous system perturbations and impacts of aging. Aged neuromuscular junctions (...
Significance
Skeletal muscle is one of the largest tissues in the body and can regenerate when damaged through a population of resident muscle stem cells. A type of muscle trauma called volumetric muscle loss overwhelms the regenerative capacity of muscle stem cells and engenders fibrotic supplantation. A comparison of muscle injuries resulting in...
Skeletal muscle has an innate regenerative capacity to restore their structure and function following acute damages and injuries. However, in congenital muscular dystrophies, large volumetric muscle loss, cachexia, or aging, the declined regenerative capacity of skeletal muscle results in muscle wasting and functional impairment. Recent studies ind...
Mesenchymal stem cells such as human adipose tissue‐derived stem cells (hADSCs) have been used as a representative therapeutic agent for tissue regeneration because of their high proliferation and paracrine factor‐secreting abilities. However, certain points regarding conventional ADSC delivery systems, such as low cell density, secreted cytokine l...
Both aging and neuromuscular diseases lead to significant changes in the morphology and functionality of the neuromuscular synapse. Skeletal muscles display a remarkable regenerative capacity, however, are still susceptible to diseases of aging and peripheral nerve perturbations. In this study, we assessed how neuromuscular synapses differ in aged...
Wireless Soft Scalp Electronics
The cover shows a wearable scalp electronic system with virtual reality for motor imagerybased brain-computer interfaces. The all-in-one, portable soft system includes an array of soft microneedles, stretchable interconnectors, and flexible circuits in a wearable platform. More details can be found in article number...
During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function impacting mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs), however, the relationship between MuSCs and innervation has not been established. He...
Motor imagery offers an excellent opportunity as a stimulus-free paradigm for brain–machine interfaces. Conventional electroencephalography (EEG) for motor imagery requires a hair cap with multiple wired electrodes and messy gels, causing motion artifacts. Here, a wireless scalp electronic system with virtual reality for real-time, continuous class...
Low cell engraftment is a major problem in tissue engineering. Although various methods related with cell sheets have been attempted to resolve the issue, low cell viability due to oxygen and nutrient depletion remains an obstacle toward advanced therapeutic applications. Cell therapy using fibroblasts is thought of as a good alternative due to the...
Volumetric muscle loss (VML) results in permanent functional deficits and remains a substantial regenerative medicine challenge. A coordinated immune response is crucial for timely myofiber regeneration, however the immune response following VML has yet to be fully characterized. Here, we leveraged dimensionality reduction and pseudo-time analysis...
Herein, a selective strain- and pressure-sensitive hydrogel-based wireless soft-electronic skin sensor with self-healing properties was designed for detection of cancer cells. The polydopamine-loaded glutathione-responsive polymer dot ([email protected]) selectivity towards CD44 receptor in hydrogel matrix was identified to play vital role in strai...
Volumetric muscle loss (VML) injuries after extremity trauma results in an important clinical challenge often associated with impaired healing, significant fibrosis, and long-term pain and functional deficits. While acute muscle injuries typically display a remarkable capacity for regeneration, critically sized VML defects present a dysregulated im...
The purpose of this study is to determine whether moderate aerobic exercise training improves high‐fat diet‐induced alterations in mitochondrial function and structure in the skeletal muscle. Male 4‐week‐old C57BL/6 mice were randomly divided into four groups: control (CON), control plus exercise (CON + EX), high‐fat diet (HFD), and high‐fat diet p...
Keratinocytes are frequently used for the biological and biomedical remodeling of damaged skin tissues. However, low cell viability, poor cell maintenance, and lack of paracrine factors hamper the therapeutic efficacy of keratinocytes for skin wound healing. Here, we report the fabrication of a 2D and 3D co-spatial compartmentalized patch (CSCP) fo...
Cell therapy based on human adipose derived stem cells (hADSCs) is a known potential therapeutic approach to induce angiogenesis in ischemic diseases. However, the therapeutic efficacy of direct hADSC injection is limited by a low cell viability and poor cell engraftment after administration. To improve the outcomes of this kind of approach, variou...
Cu/Zn Superoxide Dismutase (Sod1) catalyzes the disproportionation of cytotoxic superoxide radicals (O2-) into oxygen (O2) and hydrogen peroxide (H 2 O 2), a key signaling molecule. In Saccharomyces cer-evisiae, we previously discovered that Sod1 participates in an H2O2-mediated redox signaling circuit that links nutrient availability to the contro...
Exposure of a young systemic milieu reveals remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been reported, the exact underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the experimental challenges of using in vivo parabiosis. An in vitro parabiosis sys...
Recent advances in nanomaterials and nano-microfabrication have enabled the development of flexible wearable electronics. However, existing manufacturing methods still rely on a multi-step, error-prone complex process that requires a costly cleanroom facility. Here, we report a new class of additive nanomanufacturing of functional materials that en...
During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility and quality of life. The repair of skeletal muscle is regulated by tissue-resident stem cells called satellite cells (or muscle stem cells [MuSCs]), but in aging, MuSCs decrease in numbers and regenerative capacity. The transcriptional networks...
Regeneration of skeletal muscle after volumetric injury is thought to be impaired by a dysregulated immune microenvironment that hinders endogenous repair mechanisms. Such defects result in fatty infiltration, tissue scarring, chronic inflammation, and debilitating functional deficits. Here, we evaluated the key cellular processes driving dysregula...
Operant conditioning of Hoffmann's reflex (H-reflex) is a non-invasive and targeted therapeutic intervention for patients with movement disorders following spinal cord injury. The reflex-conditioning protocol uses electromyography (EMG) to measure reflexes from specific muscles elicited using transcutaneous electrical stimulation. Despite recent ad...
During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function in that impacts mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs), but the relationship between MuSCs and neural control has not been established...
Throughout life, skeletal muscle, the arbiter of voluntary movements, is maintained by a population of skeletal muscle-dedicated stem cells, called muscle satellite cells (MuSCs). Similar to other adult stem cells, the function of MuSCs is tightly coordinated by the cellular and acellular components of their microenvironment, or the niche. While th...
The maintenance of skeletal muscle mass depends on the overall balance between the rates of protein synthesis and degradation. Thus, age-related muscle atrophy and function, commonly known as sarcopenia, may result from decreased protein synthesis, increased proteolysis, or simultaneous changes in both processes governed by complex multifactorial m...
Mitochondrial dysfunction has been implicated in various pathologies, including muscular dystrophies. During muscle regeneration, resident stem cells, also known as muscle satellite cells (MuSCs), undergo myogenic differentiation to form de novo myofibers or fuse to existing syncytia. Leveraging this cell-cell fusion process, we postulated that mit...
The purpose of this study was to determine the effects of sarcopenic obesity (aging‐induced sarcopenia plus high fat diet‐induced obesity) and exercise training on insulin resistance, mitochondrial function (hydrogen peroxide (H 2 O 2 ) emission and calcium(Ca ²⁺ ) retention capacity) and mitochondrial dynamics (fusion; Opa1, Mfn1, Mfn2 and fission...
Muscle satellite cells (MuSCs) play an indispensable role in skeletal muscle regeneration after injury. However, their regenerative capacity declines with aging. Intriguingly, studies using parabiosis, a surgical technique that attaches two animals to share blood circulation, demonstrated that circulating factors from young animals can rejuvenate t...
Skeletal muscle regeneration is an energy‐demanding biological process that relies on mitochondria to generate ATP. While interfibrillar mitochondrial networks in healthy skeletal muscle fibers exhibit an organized architecture segregated into columns along the Z‐line of the myofiber, regenerating fibers demonstrate altered mitochondrial networks t...
Exposure of aged mice to a young systemic milieu revealed remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been identified, the exact identity and the underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the complexity of in vivo parabiosis. Here, we pre...
Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which has been recognized as a promising cancer therapeutic target. Small molecule pyrimethamine (PYM) is a known direct inhibitor of activated STAT3 and it is currently under clinical trial. Also, histone deacetylase (HDAC) inhibition has been shown to...
The extracellular matrix (ECM) serves as a microenvironmental niche providing both biophysical and biochemical signals in which cells reside and function within the body. Therefore, understanding the composition, structure, and functions of the native ECM is essential to engineering biomaterials for maintaining and/or directing cellular function fo...
Critical limb ischemia, the most severe form of peripheral artery disease, leads to extensive damage and alterations to skeletal muscle homeostasis. Although recent research has investigated the tissue-specific responses to ischemia, the role of the muscle stem cell in the regeneration of its niche components within skeletal muscle has been limited...
Skeletal muscle possesses efficient ability to regenerate upon minor injuries, but its capacity to regenerate is severely compromised with traumatic injuries and muscle-associated diseases. Recent evidence suggests that skeletal muscle regeneration can be enhanced by transplantation of muscle satellite cells (MuSCs) or treatment with pro-myogenic f...
Critical limb ischemia, the most severe form of peripheral artery disease, is a degenerative cardiovascular disease characterized by abnormal perfusion to the limbs due to occlusions of the blood vessels. Although recent developments toward revascularization therapies have been introduced, the myopathy and dysregulation of the skeletal muscle follo...
Skeletal muscle possesses a robust ability to regenerate following injury due to the presence of muscle satellite cells (MuSCs) but this capacity declines with aging. Recent in vivo studies using heterochronic parabiosis, in which two animals are surgically attached to share blood circulation, demonstrated that systemic factors in the blood of youn...
Introduction
Skeletal muscle has residential muscle stem cells, satellite cells (SC), which are indispensable for skeletal muscle regeneration and homeostasis. Previous studies highlighted the importance of SC microenvironment, or the niche, in controlling SC functions and fates. Among the SC niches, the neuronal inputs from motor neuron (MN) and n...
Skeletal muscle possesses efficient ability to regenerate upon minor injuries, but its capacity to regenerate is severely compromised with traumatic injuries and muscle-associated diseases. Recent evidence suggests that skeletal muscle regeneration can be accelerated by transplantation of muscle satellite cells (MuSCs) or treatment with pro-myogeni...
Impact statement:
The goal of this study was to determine the threshold for a critically sized, nonhealing muscle defect by characterizing key components in the balance between fibrosis and regeneration as a function of injury size in the mouse quadriceps. There is currently limited understanding of what leads to a critically sized muscle defect a...
Expanded View Figures PDF
A finely tuned balance of self-renewal, differentiation, proliferation, and survival governs the pool size and regenerative capacity of blood-forming hematopoietic stem and progenitor cells (HSPCs). Here, we report that protein kinase C delta (PKCδ) is a critical regulator of adult HSPC number and function that couples the proliferative and metabol...
The mitochondrial Ca2+ uniporter (MCU) complex mediates acute mitochondrial Ca2+ influx. In skeletal muscle, MCU links Ca2+ signaling to energy production by directly enhancing the activity of key metabolic enzymes in the mitochondria. Here, we examined the role of MCU in skeletal muscle development and metabolic function by generating mouse models...
Significance
Nanoparticle-mediated delivery of siRNA to hepatocytes has treated disease in humans. However, systemically delivering RNA drugs to nonliver tissues remains an important challenge. To increase the number of nanoparticles that could be studied in vivo, we designed a high-throughput method to measure how >100 nanoparticles delivered mRNA...
Critical limb ischemia, the most severe form of peripheral artery disease, leads to extensive damage and alterations in skeletal muscle homeostasis. Although recent developments towards revascularization therapies have been introduced, there has been limited research into treatments for ischemic myopathy. To elucidate the regenerative mechanism of...
Muscle satellite cells (MuSCs) play a central role in muscle regeneration, but their quantity and function decline with comorbidity of trauma, aging, and muscle diseases. Although transplantation of MuSCs in traumatically injured muscle in the comorbid context of aging or pathology is a strategy to boost muscle regeneration, an effective cell deliv...
Skeletal muscle has a remarkable regenerative capacity; however, after volumetric muscle loss (VML) due to traumatic injury or surgery this regenerative response is significantly diminished, causing chronic functional deficits. The critical defect size at which the muscle will not functionally recover has not yet been established and subsequently,...
High-density lipoprotein (HDL) is a key regulator of lipid homeostasis through its native roles like reverse cholesterol transport. The reconstitution of this natural nanoparticle (NP) has become a nexus between nanomedicine and multi-disease therapies, for which a major portion of HDL functionality is attributed to its primary scaffolding protein,...
Elevation of anabolism and concurrent suppression of catabolism are critical metabolic adaptations for muscular hypertrophy in response to resistance exercise (RE). Here, we investigated if RE-induced muscular hypertrophy is acquired by modulating a critical catabolic process autophagy. Male Wistar Hannover rats (14 weeks old) were randomly assigne...
Following injury, adult skeletal muscle undergoes a well-coordinated sequence of molecular and physiological events to promote repair and regeneration. However, a thorough understanding of the in vivo epigenomic and transcriptional mechanisms that control these reparative events is lacking. To address this, we monitored the in vivo dynamics of thre...
Regeneration of traumatically injured skeletal muscles is severely limited. Moreover, the regenerative capacity of skeletal muscle declines with aging, further exacerbating the problem. Recent evidence support that delivery of muscle satellite cells to the injured muscles enhances muscle regeneration and reverses features of aging, including reduct...
Genetic ablation of CuZn-superoxide dismutase (Sod1) in mice (Sod1−/− mice) leads to shortened lifespan with a dramatic increase in hepatocellular carcinoma and accelerated aging phenotypes, including early onset sarcopenia. To study the tissue specific effects of oxidative stress in the Sod1−/− mice, we generated mice that only express the human S...
Normal repair of skeletal muscle requires local expansion of a special population of Foxp3+CD4+ regulatory T (Treg) cells. Such cells failed to accumulate in acutely injured muscle of old mice, known to undergo ineffectual repair. This defect reflected reduced recruitment of Treg cells to injured muscle, as well as less proliferation and retention...