A5006680498- Muscle Physiology and Disorders
- Nuclear Structure and Function
- Cardiomyopathy and Myosin Studies
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Cellular transport and secretion
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Trace Elements in Health
- RNA modifications and cancer
- Cell Adhesion Molecules Research
- Selenium in Biological Systems
- Heavy Metal Exposure and Toxicity
- Glycogen Storage Diseases and Myoclonus
- Inflammatory Myopathies and Dermatomyositis
- Cardiovascular Effects of Exercise
- Biochemical and Molecular Research
- Congenital heart defects research
- Metabolism, Diabetes, and Cancer
- Silk-based biomaterials and applications
- Ubiquitin and proteasome pathways
- Knee injuries and reconstruction techniques
- Signaling Pathways in Disease
- Erythrocyte Function and Pathophysiology
- Cardiac Fibrosis and Remodeling
Harvard University
2007-2025
Boston Children's Hospital
2013-2025
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2009-2025
University of Massachusetts Boston
2023
Boston Children's Museum
2019
John Wiley & Sons (United States)
2018
Hudson Institute
2018
University of Virginia
2018
University of Copenhagen
2002-2003
Institut de Myologie
2001-2002
Replacing or editing disease-causing mutations holds great promise for treating many human diseases. Yet, delivering therapeutic genetic modifiers to specific cells in vivo has been challenging, particularly large, anatomically distributed tissues such as skeletal muscle. Here, we establish an strategy evolve and stringently select capsid variants of adeno-associated viruses (AAVs) that enable potent delivery desired tissues. Using this method, identify a class RGD motif-containing capsids...
Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression ADAM12, disintegrin and metalloprotease, dramatically affects morphology preadipocytes, changing them from flattened, fibroblastic appearance to more rounded shape. We showed highest levels ADAM12 mRNA were detected preadipocytes at critical stage when become permissive for adipogenic Furthermore, as assessed by immunostaining, was transiently expressed surface concomitant with...
Congenital and inherited myopathies in dogs are faithful models of human muscle diseases being recognized with increasing frequency. In fact, canine dystrophin deficient muscular dystrophy X-linked myotubular myopathy tremendous value the translation new promising therapies for treatment these diseases. We have recently identified a family Australian Rottweilers which male puppies were clinically affected severe weakness atrophy that resulted early euthanasia or death. was suspected based on...
Significance Mature cardiomyocytes are highly adapted to pump efficiently over billions of cycles. The mechanisms that regulate and coordinate the acquisition specialized features mature in postnatal period not well understood. This knowledge gap hinders studies disease pathogenesis maturation stem cell–derived for cardiac regenerative medicine. Here, we studied roles sarcomeres, contractile machinery cardiomyocytes, regulating cardiomyocyte maturation. Using an vivo genetic mosaic approach...
Congenital fiber type disproportion (CFTD) is a rare congenital myopathy characterized by hypotonia and generalized muscle weakness. Pathologic diagnosis of CFTD based on the presence 1 hypotrophy at least 12% in absence other notable pathological findings. Mutations ACTA1 SEPN1 genes have been identified small percentage cases. The tropomyosin 3 gene, TPM3, mutated cases nemaline that typically exhibit with rods, recently mutations TPM3 gene were also found to cause CFTD. We screened...
Cardiac sodium channel Nav1.5 plays a critical role in heart excitability and conduction. The molecular mechanism that underlies the expression of at cell membrane is poorly understood. Previous studies demonstrated cytoskeleton proteins can be involved regulation surface localization several ion channels. We performed yeast two-hybrid screen to identify Nav1.5-associated may function expression. identified α-actinin-2 as an interacting partner cytoplasmic loop connecting domains III IV...
Abstract Inclusion body myositis (IBM) is an inflammatory disease of skeletal muscle unknown cause. To further understand the nature tissue injury in this disease, we developed methods for large‐scale detection and quantitation proteins biopsy samples analyzed proteomic data produced by these together with histochemical, immunohistochemical, microarray data. Twenty from patients myopathies ( n = 17) or elderly subjects without neuromuscular 3) were profiled studies using liquid...
Mutations in the human SEPN1 gene, encoding selenoprotein N (SepN), cause SEPN1-related myopathy (SEPN1-RM) characterized by muscle weakness, spinal rigidity, and respiratory insufficiency. As with other members of family, incorporates selenium form selenocysteine (Sec). Most selenoproteins that have been functionally are involved oxidation-reduction (redox) reactions, Sec residue located at their catalytic site. To model SEPN1-RM, we generated a Sepn1-knockout (Sepn1–/–) mouse line....
SELENON-Congenital Myopathy (SELENON-CM) is a rare congenital myopathy caused by mutations of the SELENON gene characterized axial muscle weakness and progressive respiratory insufficiency. Muscle histopathology may be non-specific, but commonly includes multiminicores or dystrophic pattern. The encodes selenoprotein N (SelN), selenocysteine-containing redox enzyme located in endo/sarcoplasmic reticulum membrane where it colocalizes with mitochondria-associated membranes. However, molecular...
Mouse models for genetic diseases are among the most powerful tools available developing and testing new treatment strategies. ADAM12 is a disintegrin metalloprotease, previously demonstrated to significantly alleviate pathology of mdx mice, model Duchenne muscular dystrophy in humans. More specifically appeared prevent muscle cell necrosis mice as evidenced by morphological analysis reduced levels serum creatine kinase. In present study we that may compensate dystrophin deficiency...
A 45-year-old man with severe proximal muscle weakness had findings diagnostic of adult-onset nemaline myopathy. He also a monoclonal gammopathy. This is the fifth report myopathy in patient gammopathy, suggesting that occurrence these entities may be more than chance association. Myocyte-bound immunoglobulin or light chains were not detected and immunotherapy was effective this patient. Other causes ruled out, including most common mutations sarcomeric thin filament genes.
Adenylosuccinic acid (ASA) is an orphan drug that was once investigated for clinical application in Duchenne muscular dystrophy (DMD). Endogenous ASA participates purine recycling and energy homeostasis but might also be crucial averting inflammation other forms of cellular stress during intense demand maintaining tissue biomass glucose disposal. This article documents the known biological functions explores its potential treatment neuromuscular chronic diseases.
The inaugural Clinical and Scientific Conference on Adenylosuccinate Synthetase 1 (ADSS1) myopathy was held June 3, 2024, at the National Institutes of Health (NIH) Center for Advancing Translational Sciences (NCATS) in Rockville, Maryland, USA. ADSS1 is an ultra-rare, inherited neuromuscular disease. Features geographical patient clusters South Korea, Japan, India United States America were characterised discussed. Pre-clinical animal cell-based models discussed, providing unique insight...
Abstract We describe a second large Italian kindred with autosomal dominant vacuolar myopathy characterized by variable severity, adult‐onset weakness of distal limb muscles, and no cardiac involvement. At least 19 individuals over four generations are affected. Histopathological immunochemical features the vacuoles, present in many fibers, indicate protein degradation abnormalities dysregulation lysosomal pathway activation ubiquitin‐proteasomal pathway. Linkage analysis localized defect to...