A5053739317- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Neurogenetic and Muscular Disorders Research
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Congenital heart defects research
- Virus-based gene therapy research
- Genetic Neurodegenerative Diseases
- Lysosomal Storage Disorders Research
- Sphingolipid Metabolism and Signaling
- Zebrafish Biomedical Research Applications
- Ion channel regulation and function
- Histone Deacetylase Inhibitors Research
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Metabolism and Genetic Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Gout, Hyperuricemia, Uric Acid
- Spaceflight effects on biology
- Genetics and Neurodevelopmental Disorders
- Telomeres, Telomerase, and Senescence
- Myofascial pain diagnosis and treatment
- Pharmacological Receptor Mechanisms and Effects
- Viral Infectious Diseases and Gene Expression in Insects
- Hereditary Neurological Disorders
Sichuan University
2024-2025
West China Hospital of Sichuan University
2024-2025
Chinese Academy of Medical Sciences & Peking Union Medical College
2024-2025
Medical College of Wisconsin
2014-2024
First Hospital of Shanxi Medical University
2017
Shanxi Medical University
2017
Beijing University of Chinese Medicine
2017
Army Medical University
2009-2015
China Medical University
2011
Southwest Hospital
2009
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin, membrane-stabilizing protein encoded DMD gene. Although mouse models provide insight into potential corrective therapy, data from genetically homologous large animals, such as dystrophin-deficient golden retriever (GRMD) model, may more readily translate to humans. To evaluate clinical translatability an adeno-associated virus serotype 9 vector (AAV9)–microdystrophin (μDys5)...
X-linked myotubular myopathy (XLMTM) results from MTM1 gene mutations and myotubularin deficiency. Most XLMTM patients develop severe muscle weakness leading to respiratory failure death, typically within 2 years of age. Our objective was evaluate the efficacy safety systemic therapy in p.N155K canine model by performing a dose escalation study. A recombinant adeno-associated virus serotype 8 (rAAV8) vector expressing (cMTM1) under muscle-specific desmin promoter (rAAV8-cMTM1) administered...
No effective treatment exists for patients with X-linked myotubular myopathy (XLMTM), a fatal congenital muscle disease caused by deficiency of the lipid phosphatase, myotubularin. The Mtm1δ4 and Mtm1 p.R69C mice model severely moderately symptomatic XLMTM, respectively, due to differences in degree myotubularin deficiency. Contractile function intact extensor digitorum longus (EDL) soleus muscles from mice, which produce no myotubularin, is markedly impaired. forces generated chemically...
Skeletal muscle is a unique tissue because of its structure and function, which requires specific protocols for collection to obtain optimal results from functional, cellular, molecular, pathological evaluations. Due the subtlety some abnormalities seen in congenital disorders potential fixation interfere with recognition these features, evaluation frozen preferable fixed when evaluating skeletal disease. Additionally, produce severe freezing artifacts precautions histological examination...
Abstract Neural stem/progenitor cells (NSPCs) replacement therapies are the most attractive strategies to restore an injured brain. Key challenges of such enriching NSPCs and directing them differentiation into specific neural cell types. Here, three biomaterial substrates Poly-L-ornithine (PO), Poly-L-lysine (PLL) fibronectin (FN) were investigated for their effects on proliferation rat underlying mechanisms also explored. The results showed PO significantly increased induced preferred...
Nebulin—a giant sarcomeric protein—plays a pivotal role in skeletal muscle contractility by specifying thin filament length and function. Although mutations the gene encoding nebulin (NEB) are frequent cause of nemaline myopathy, most common non-dystrophic congenital mechanisms which NEB weakness remain largely unknown. To better understand these mechanisms, we have generated mouse model Neb exon 55 is deleted (NebΔExon55) to replicate founder mutation seen frequently patients with myopathy...
Nebulin is a giant filamentous protein that coextensive with the actin filaments of skeletal muscle sarcomere. mutations are main cause nemaline myopathy (NEM), typical adult patients having low expression nebulin, yet roles nebulin in remain poorly understood. To establish nebulin's functional muscle, we studied novel conditional KO (Neb cKO) mouse model which deletion was driven by creatine kinase (MCK) promotor. Neb cKO mice born high levels their muscles, but within weeks after birth...
X-linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of protein myotubularin, results from mutations in MTM1 gene. While there is no cure for XLMTM, we previously reported effects gene therapy using adeno-associated virus (AAV) vector on muscle weakness and pathology MTM1-mutant dogs. Here, followed 2 AAV-infused dogs over 4 years.We evaluated gait, strength, respiration, neurological function, pathology, AAV copy number (VCN), transgene expression.Four...
Friedreich's ataxia (FRDA) is an autosomal-recessive disorder primarily attributed to biallelic GAA repeat expansions that reduce expression of the mitochondrial protein frataxin (FXN). FRDA characterized by progressive neurodegeneration, with many patients developing cardiomyopathy progresses heart failure and death. The potential reverse or prevent progression cardiac phenotype was investigated in a mouse model FRDA, using adeno-associated viral vector (AAV8) containing coding sequence FXN...
X-linked myotubular myopathy is a severe congenital caused by deficiency of the lipid phosphatase, myotubularin. Recent studies human tissue and animal models have discovered structural physiological abnormalities in myotubularin-deficient muscle, but impact myotubularin on myogenic stem cells within muscles unclear. In present study, we evaluated viability, proliferative capacity, vivo engraftment obtained from severely symptomatic (Mtm1δ4) mice. Mtm1δ4 muscle contains fewer than wild-type...
X-linked myotubular myopathy is a congenital caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy 2b myofibers and modest increases strength life span in the severely myopathic Mtm1δ4 mouse model myopathy. have now performed similar study less symptomatic Mtm1 p.R69C hopes finding greater...
Nemaline myopathy (NM) is a heterogeneous congenital skeletal muscle disease with cytoplasmic rod-like structures (nemaline bodies) in tissue. While weakness NM related to contractile abnormalities, myofiber smallness an additional abnormality that may be treatable. We evaluated the effects of mRK35 (a myostatin inhibitor developed by Pfizer) treatment TgACTA1D286G mouse model NM. induced growth led significant increases animal bodyweight, forelimb grip strength and fiber force, although it...
Abstract Loss of GABAergic inhibition in pain pathways has been considered to be a key component the development chronic pain. In present study, we intended examine whether miR-92b–mediated posttranscriptional dysregulation spinal potassium chloride cotransporter (KCC2) and vesicular γ-aminobutyric acid transporter (VGAT) plays major role maintenance long-term visceral hyperalgesia neonatal zymosan–treated rats. Neonatal cystitis was induced by transurethral zymosan administration from...
Abstract The sigma‐1 receptor (σ1R) is a stress‐activated chaperone protein that has emerged as significant therapeutic target for neurodegenerative disorders. Developing effective positron emission tomography (PET) imaging probes targeting σ1R crucial visualizing its distribution and function in the brain, well facilitating related drug development. In this study, two novel 11 C‐labeled PET based on structure of potent ligand Lan‐0101 are designed synthesized. studies mice reveal [ C]CNY‐01...
Abstract Sphingosine‐1‐phosphate (S1P) binds to G protein–coupled receptors and can regulate a wide range of cellular functions. In previous study, we isolated two key enzymes in the S1P pathway that were expressed migrating neural crest cells. To determine if are present cells or peripheral nervous system, examine expression patterns ( S1pr1‐5 ) mouse, s1pr1 s1pr3 chick embryos. Here, comprehensive analysis these using situ hybridizations, which provide spatiotemporal information. We showed...
Lysophospholipids such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are important signaling molecules that can regulate a wide range of cellular responses. We discovered Sphingosine kinase 1 (Sphk1), key enzyme converts sphingosine to S1P, is expressed in neurons progenitor cells nascent trigeminal dorsal root ganglia during mouse embryogenesis.Sphk1 null embryos do not display overt deficits owing compensation by Sphk2. Thus, we analyzed deficient both Sphk1 Sphk2 (which...
X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital characterized by profound skeletal muscle weakness, respiratory distress, and motor dysfunction. However, pathology not limited to can be associated with hepatic peliosis. Hepatobiliary disease has been reported in up 17% of XLMTM patients but extensively characterized. We report on five who experienced intrahepatic cholestasis their natural history, illustrating the need further investigate these manifestations....
Tetraspanins are a family of proteins known to assemble protein complexes at the cell membrane. They thought play diverse cellular functions in tissues by modifying protein-binding partners, thus bringing complexity and diversity their regulatory networks. Previously, we identified tetraspanin KAI/CD82 as prospective marker for human muscle stem cells. CD82 expression appeared decreased Duchenne muscular dystrophy (DMD) muscle, suggesting functional link dystrophy, yet whether this decrease...