A5050734640- Muscle Physiology and Disorders
- Axon Guidance and Neuronal Signaling
- Cardiomyopathy and Myosin Studies
- Neurogenesis and neuroplasticity mechanisms
- Silk-based biomaterials and applications
- Exercise and Physiological Responses
- Neurogenetic and Muscular Disorders Research
- Cell Adhesion Molecules Research
- Tissue Engineering and Regenerative Medicine
- Muscle activation and electromyography studies
- RNA Research and Splicing
- Nerve injury and regeneration
- Developmental Biology and Gene Regulation
- Adipose Tissue and Metabolism
- Genomics and Rare Diseases
- Medical Imaging and Pathology Studies
- Genetics and Neurodevelopmental Disorders
- Occupational and environmental lung diseases
- TGF-β signaling in diseases
- RNA modifications and cancer
- Cellular Mechanics and Interactions
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Extracellular vesicles in disease
- Genetic Syndromes and Imprinting
Boston Children's Hospital
2020-2023
University of Nevada, Reno
2014-2022
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a dramatic neuromuscular disease in which crippling muscle weakness evident from birth. Here, we use the dyW mouse model for human MDC1A to trace onset of during development utero. We find that myotomal and primary myogenesis proceed normally homozygous dyW-/- embryos. Fetal muscles display same number myofibers as wildtype (WT) muscles, but by E18.5 are significantly smaller size not recovered post-natally. These results...
Oculomotor neurons develop initially like typical motor neurons, projecting axons out of the ventral midbrain to their ipsilateral targets, extraocular muscles. However, in all vertebrates, after oculomotor nerve (nIII) has reached muscle primordia, cell bodies that innervate superior rectus migrate join contralateral nucleus. This neuron migration represents a unique strategy form projection. Whether is guided by diffusible cues remains unknown. We examined role Slit chemorepellent signals...
Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In muscle, integrin plays an important role during muscle development has been described as modifier of diseases. The also highly expressed the heart, but its precise function unknown. Mutations α7 gene ( ITGA7 ) have reported children with congenital myopathy. Methods Results this study, we pathology Itga7 −/− mice 5 patients from 2 unrelated families mutations. Proband family 1 presented homozygous...
Duchenne muscular dystrophy (DMD) is a lethal, muscle degenerative disease causing premature death of affected children. DMD characterized by mutations in the dystrophin gene that result loss protein. Loss causes an associated reduction proteins glycoprotein complex, leading to contraction-induced sarcolemmal weakening, tearing, fibrotic infiltration and rounds degeneration failed regeneration affecting satellite cell populations. The α7β1 integrin has been implicated increasing myogenic...
Abstract Duchenne muscular dystrophy (DMD) is a devastating X-linked disease affecting ~1 in 5000 males. DMD patients exhibit progressive muscle degeneration and weakness, leading to loss of ambulation premature death from cardiopulmonary failure. We previously reported that mouse Laminin-111 (msLam-111) protein could reduce pathology improve function the mdx model for DMD. In this study, we examined ability msLam-111 prevent progression golden retriever (GRMD) dog The was injected into...
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...
Peptidyl-tRNA hydrolase 2 (PTRH2) regulates integrin-mediated pro-survival and apoptotic signaling. PTRH2 is critical in muscle development myogenic differentiation. In humans a biallelic mutation the gene causes infantile-onset multisystem disease with progressive weakness. We report here that Ptrh2 knockout mouse model recapitulates congenital pathology observed patients. null mice demonstrate multiple degenerating regenerating fibers, increased central nuclei, elevated creatine kinase...
Kabuki syndrome (KS) is a rare genetic disorder caused primarily by mutations in the histone modifier genes KMT2D and KDM6A. The have broad temporal spatial expression many organs, resulting complex phenotypes observed KS patients. Hypotonia one of clinical presentations associated with KS, yet detailed examination skeletal muscle samples from patients has not been reported. We studied consequences loss function both mouse human muscles. In mice, heterozygous Kmt2d resulted reduced...
Abstract Tetraspanins organize protein complexes at the cell membrane and are responsible for assembling diverse binding partners in changing cellular states. Tetraspanin CD82 is a useful surface marker prospective isolation of human myogenic progenitors its expression decreased Duchenne muscular dystrophy (DMD) lines. The function skeletal muscle remains elusive, partly because this tetraspanin cells have not been identified. CD82‐associated proteins sought to be identified myotubes via...
ABSTRACT Extracellular matrix (ECM) myopathies and muscular dystrophies are a group of genetic diseases caused by mutations in genes encoding proteins that provide critical links between muscle cells the extracellular matrix. These include structural ECM, cell receptors, enzymes, intracellular proteins. Loss adhesion within myomatrix results progressive weakness. For many ECM dystrophies, symptoms can occur any time after birth often result reduced life expectancy. There no cures for...