A5085244624- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Adipose Tissue and Metabolism
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Legionella and Acanthamoeba research
- Bacterial biofilms and quorum sensing
- Advanced Sensor and Energy Harvesting Materials
- Ubiquitin and proteasome pathways
- Tissue Engineering and Regenerative Medicine
- Transcranial Magnetic Stimulation Studies
- Muscle metabolism and nutrition
University of Minnesota
2016-2020
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2020
National Institutes of Health
2020
Institute of Molecular Biology and Biophysics
2017
Delivery of miniaturized dystrophin genes via adeno-associated viral vectors is one leading approach in development to treat Duchenne muscular dystrophy. Here we directly compared the functionality five mini- and micro-dystrophins skeletal muscle-specific transgenic expression dystrophin-deficient mdx mice. We evaluated their ability rescue defects microtubule network, passive stiffness contractility muscle. Transgenic mice expressing short isoform Dp116 served as a negative control. All...
Absence of the protein dystrophin causes Duchenne muscular dystrophy. Dystrophin directly binds to microtubules in vitro, and its absence vivo correlates with disorganization subsarcolemmal microtubule lattice, increased detyrosination α-tubulin, altered redox signaling. We previously demonstrated that homologue utrophin neither vitro nor rescues lattice organization when overexpressed muscles dystrophin-deficient mdx mice. Here, we fine-mapped domain necessary for binding spectrin-like...
Missense mutations in the dystrophin protein can cause Duchenne muscular dystrophy (DMD) or Becker (BMD) through an undefined pathomechanism. In vitro studies suggest that missense N-terminal actin-binding domain (ABD1) instability, and cultured myoblast reveal decreased expression levels be restored to wild-type with proteasome inhibitors. To further elucidate pathophysiology of vivo, we generated two transgenic mdx mouse lines expressing L54R L172H mutant dystrophin, which correspond...
The highly ordered cortical microtubule lattice of skeletal muscle is disorganized in dystrophin-deficient mdx mice. Implicated mechanisms include loss dystrophin binding, altered α-tubulin posttranslational modification, expression a β-tubulin involved regeneration, and reactive oxygen species (ROS). Here we show that the transverse microtubules expressing miniaturized dystrophins are rapidly lost after eccentric contraction. Analysis lines different constructs demonstrate spectrin-like...
While α‐actin isoforms predominate in adult striated muscle, skeletal muscle‐specific knockouts (KOs) of nonmuscle cytoplasmic β cyto ‐ or γ ‐actin each cause a mild, but progressive myopathy effected by an unknown mechanism. Using transmission electron microscopy, we identified morphological abnormalities both the mitochondria and sarcoplasmic reticulum (SR) aged KO mice. We found proteins to be enriched isolated mitochondrial‐associated membrane preparations, which represent interface...
AMPylation, the post-translational modification with adenosine monophosphate (AMP), is catalyzed by effector proteins from a variety of pathogens. Legionella pneumophila thus far only known pathogen that, in addition to encoding an AMPylase (SidM/DrrA), also encodes deAMPylase, called SidD, that reverses SidM-mediated AMPylation vesicle transport GTPase Rab1. DeAMPylation N-terminal phosphatase-like domain SidD. Here, we determined crystal structure full length SidD including uncharacterized...