Prominent publications by Michele Hadhazy

KOL Index score: 11592

In the vasculature, ATP-sensitive potassium channels (KATP) channels regulate vascular tone. Mice with targeted gene disruptions of KATP subunits expressed in vascular smooth muscle develop spontaneous coronary vascular spasm and sudden death. From these models, it was hypothesized that the loss of KATP channel activity in arterial vascular smooth muscle was responsible for coronary artery spasm. We now tested this hypothesis using a transgenic strategy where the full-length sulfonylurea ...

Also Ranks for: Coronary Vasospasm |  mutant mice |  smooth muscle |  katp channels |  sulfonylurea receptor
KOL Index score: 10429

Muscle growth occurs during embryonic development and continues in adult life as regeneration. During embryonic muscle growth and regeneration in mature muscle, singly nucleated myoblasts fuse to each other to form myotubes. In muscle growth, singly nucleated myoblasts can also fuse to existing large, syncytial myofibers as a mechanism of increasing muscle mass without increasing myofiber number. Myoblast fusion requires the alignment and fusion of two apposed lipid bilayers. The repair ...

Also Ranks for: Fusion Myoblasts |  muscle growth |  embryonic development |  protein dysferlin |  null mice
KOL Index score: 9984

Most single-gene diseases, including muscular dystrophy, display a nonuniform phenotype. Phenotypic variability arises, in part, due to the presence of genetic modifiers that enhance or suppress the disease process. We employed an unbiased mapping approach to search for genes that modify muscular dystrophy in mice. In a genome-wide scan, we identified a single strong locus on chromosome 7 that influenced two pathological features of muscular dystrophy, muscle membrane permeability and ...

Also Ranks for: Muscular Dystrophy |  latent tgf |  knockout mice |  binding protein |  muscle fibrosis
KOL Index score: 9924

Sarcoglycan is a multimeric, integral membrane glycoprotein complex that associates with dystrophin. Mutations in individual sarcoglycan subunits have been identified in inherited forms of muscular dystrophy. To evaluate the contributions of sarcoglycan and dystrophin to muscle membrane stability and muscular dystrophy, we compared muscle lacking specific sarcoglycans or dystrophin. Here we report that mice lacking (delta)-sarcoglycan developed muscular dystrophy and cardiomyopathy ...

Also Ranks for: Glycoprotein Complex |  knockout models |  mdx mice |  muscle membrane |  muscular dystrophy
KOL Index score: 9706

Latent TGFβ binding proteins (LTBPs) regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying ...

Also Ranks for: Muscular Dystrophy |  latent tgfβ |  binding protein |  muscle mass |  mdx mice
KOL Index score: 9427

Dysferlin is a membrane-associated protein implicated in muscular dystrophy and vesicle movement and function in muscles. The precise role of dysferlin has been debated, partly because of the mild phenotype in dysferlin-null mice (Dysf). We bred Dysf mice to mice lacking myoferlin (MKO) to generate mice lacking both myoferlin and dysferlin (FER). FER animals displayed progressive muscle damage with myofiber necrosis, internalized nuclei, and, at older ages, chronic remodeling and ...

Also Ranks for: Dysferlin Myoferlin |  muscular dystrophy |  dysf mice |  transverse tubule |  sarcoplasmic reticulum
KOL Index score: 9195

Mutations in the gene encoding the inner nuclear membrane proteins lamins A and C produce cardiac and skeletal muscle dysfunction referred to as Emery Dreifuss muscular dystrophy. Lamins A and C participate in the LINC complex that, along with the nesprin and SUN proteins, LInk the Nucleoskeleton with the Cytoskeleton. Nesprins 1 and 2 are giant spectrin-repeat containing proteins that have large and small forms. The nesprins contain a transmembrane anchor that tethers to the nuclear ...

Also Ranks for: Muscular Dystrophy |  emery dreifuss |  linc complex |  nuclear membrane |  inbred c57bl mice
KOL Index score: 8902

Glucocorticoid steroids such as prednisone are prescribed for chronic muscle conditions such as Duchenne muscular dystrophy, where their use is associated with prolonged ambulation. The positive effects of chronic steroid treatment in muscular dystrophy are paradoxical because these steroids are also known to trigger muscle atrophy. Chronic steroid use usually involves once-daily dosing, although weekly dosing in children has been suggested for its reduced side effects on behavior. In ...

Also Ranks for: Muscle Atrophy |  steroid dosing |  muscular dystrophy |  inbred dba mice |  intermittent glucocorticoid
KOL Index score: 8041

The sarcoglycan complex is found normally at the plasma membrane of muscle. Disruption of the sarcoglycan complex, through primary gene mutations in dystrophin or sarcoglycan subunits, produces membrane instability and muscular dystrophy. Restoration of the sarcoglycan complex at the plasma membrane requires reintroduction of the mutant sarcoglycan subunit in a manner that will permit normal assembly of the entire sarcoglycan complex. To study sarcoglycan gene replacement, we introduced ...

Also Ranks for: Muscular Dystrophy |  sarcoglycan complex |  plasma membrane |  dystrophin gene |  transgenic muscle
KOL Index score: 6956

Myostatin, a TGF-beta family member, is a negative regulator of muscle growth. Here, we generated transgenic mice that expressed myostatin mutated at its cleavage site under the control of a muscle specific promoter creating a dominant negative myostatin. These mice exhibited a significant (20-35%) increase in muscle mass that resulted from myofiber hypertrophy and not from myofiber hyperplasia. We also evaluated the role of myostatin in muscle degenerative states, such as muscular ...

Also Ranks for: Muscle Myostatin |  dominant negative |  hypertrophy hyperplasia |  transgenic mice |  muscular dystrophy
KOL Index score: 6952

Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and latent TGFβ binding protein 4 (LTBP4). We now evaluated the functional effect of these modifiers in the context of muscle injury and repair to elucidate their mechanisms of ...

Also Ranks for: Muscular Dystrophy |  genetic modifiers |  knockout muscle |  latent tgfβ |  beta binding
KOL Index score: 6480

BACKGROUND: Cardiomyopathy and arrhythmias are under significant genetic influence. Here, we studied a family with dilated cardiomyopathy and associated conduction system disease in whom prior clinical cardiac gene panel testing was unrevealing.

METHODS: Whole-genome sequencing and induced pluripotent stem cells were used to examine a family with dilated cardiomyopathy and atrial and ventricular arrhythmias. We also characterized a mouse model with heterozygous and homozygous deletion of ...

Also Ranks for: Dilated Cardiomyopathy |  mybphl mice |  ventricular function |  atria heart |  mouse model
KOL Index score: 6324

Exon skipping uses antisense oligonucleotides as a treatment for genetic diseases. The antisense oligonucleotides used for exon skipping are designed to bypass premature stop codons in the target RNA and restore reading frame disruption. Exon skipping is currently being tested in humans with dystrophin gene mutations who have Duchenne muscular dystrophy. For Duchenne muscular dystrophy, the rationale for exon skipping derived from observations in patients with naturally occurring ...

Also Ranks for: Muscular Dystrophy |  exon skipping |  transgenic muscle |  γ sarcoglycan |  antisense oligonucleotides
KOL Index score: 6218

Latent transforming growth factor-β (TGFβ) binding proteins (LTBPs) bind to inactive TGFβ in the extracellular matrix. In mice, muscular dystrophy symptoms are intensified by a genetic polymorphism that changes the hinge region of LTBP, leading to increased proteolytic susceptibility and TGFβ release. We have found that the hinge region of human LTBP4 was also readily proteolysed and that proteolysis could be blocked by an antibody to the hinge region. Transgenic mice were generated to ...

Also Ranks for: Muscular Dystrophy |  latent tgfβ |  hinge region |  transgenic mice |  muscle damage
KOL Index score: 6140

Vascular spasm is a poorly understood but critical biomedical process because it can acutely reduce blood supply and tissue oxygenation. Cardiomyopathy in mice lacking gamma-sarcoglycan or delta-sarcoglycan is characterized by focal damage. In the heart, sarcoglycan gene mutations produce regional defects in membrane permeability and focal degeneration, and it was hypothesized that vascular spasm was responsible for this focal necrosis. Supporting this notion, vascular spasm was noted in ...

Also Ranks for: Smooth Muscle |  vascular spasm |  cardiac myocytes |  sarcoglycan complex |  mice mice

Key People For Muscular Dystrophy

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Louis * ******
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Kevin * ********
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Volker * ******
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Jerry * *******
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Michele Hadhazy:Expert Impact

Concepts for whichMichele Hadhazyhas direct influence:Muscular dystrophy,  Vascular spasm,  Genetic modifiers,  Sulfonylurea receptor,  Skeletal muscle,  Skeletal muscular dystrophy,  Knockout mice,  Latent tgfβ.

Michele Hadhazy:KOL impact

Concepts related to the work of other authors for whichfor which Michele Hadhazy has influence:Skeletal muscle,  Muscular dystrophy,  Nuclear envelope,  Myoblast fusion,  Mdx mice,  Membrane repair,  Myostatin gene.



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Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States of America | Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USA. | Center for Genetic Medicine, Northwestern University