A5026421450- Muscle Physiology and Disorders
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Neurological diseases and metabolism
- Genetic Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- Adipose Tissue and Metabolism
- Parkinson's Disease Mechanisms and Treatments
- Cardiomyopathy and Myosin Studies
- Lysosomal Storage Disorders Research
- Biotin and Related Studies
- Genetics and Neurodevelopmental Disorders
- Prion Diseases and Protein Misfolding
- Osteoarthritis Treatment and Mechanisms
- Telomeres, Telomerase, and Senescence
- Genetics and Physical Performance
- Entomopathogenic Microorganisms in Pest Control
- Calpain Protease Function and Regulation
- Cellular Mechanics and Interactions
- Cancer-related gene regulation
- Nicotinic Acetylcholine Receptors Study
- RNA regulation and disease
- Cell Adhesion Molecules Research
Stony Brook University
2017-2025
University of Maine
2014-2017
Jackson Laboratory
2005-2012
University of California, Davis
2000
Congenital muscular dystrophy is a heterogeneous group of inherited muscle diseases characterized clinically by weakness and hypotonia in early infancy. A number genes harboring causative mutations have been identified, but several cases congenital remain molecularly unresolved. We examined 15 individuals with early-onset wasting, mental retardation, peculiar enlarged mitochondria that are prevalent toward the periphery fibers sparse center on biopsy, we identified homozygous or compound...
A hallmark of neurodegeneration is defective protein quality control. The E3 ligase Listerin (LTN1/Ltn1) acts in a specialized control pathway-Ribosome-associated Quality Control (RQC)-by mediating proteolytic targeting incomplete polypeptides produced by ribosome stalling, and Ltn1 mutation leads to mice. Whether results from RQC whether contributes human disease have remained unknown. Here we show that three independently-generated mouse models with mutations different component the...
Abstract Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, which associated with neuroinflammation and reactive gliosis. The underlying cause PD concurrent are not well understood. In this study, we utilize human murine neuronal lines, stem cell‐derived neurons, mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, GBA, components a single gene regulatory pathway. Our...
The effective treatment or cure of motoneuron disease will require understanding the processes that precede irreversible cell loss. To study these early stages, and to evaluate potential treatments in relevant animal models, requires a sensitive functional assay. this end, we sought determine whether gait pattern SOD1 transgenic mice changed prior overt symptoms. Using simplified video-based approach compared treadmill C57BL/6J B6.SOD1 at 8 10 weeks age. had significantly longer stride...
Choline kinase is the first step enzyme for phosphatidylcholine (PC) de novo biosynthesis. Loss of choline activity in muscle causes rostrocaudal muscular dystrophy (rmd) mouse and congenital human, characterized by distinct mitochondrial morphological abnormalities. We performed biochemical pathological analyses on skeletal mitochondria from rmd mice. No were found center fibers, while those located at periphery fibers significantly enlarged. Muscle mice exhibited decreased PC levels,...
A GGGGCC (G4C2) hexanucleotide repeat expansion in C9ORF72 causes amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), while a CGG trinucleotide FMR1 leads to the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). These GC-rich repeats form RNA secondary structures that support repeat-associated non-AUG (RAN) translation of toxic proteins contribute disease pathogenesis. Here we assessed whether these same might trigger stalling interfere with...
Muscular dystrophies include a diverse group of genetically heterogeneous disorders that together affect 1 in 2000 births worldwide. The diseases are characterized by progressive muscle weakness and wasting lead to severe disability often premature death. Rostrocaudal muscular dystrophy (rmd) is new recessive mouse mutation causes rapidly neonatal forelimb bone deformity. rmd 1.6-kb intragenic deletion within the choline kinase beta (Chkb) gene, resulting complete loss CHKB protein enzymatic...
Abstract Neurodegenerative diseases (NDDs) and other age-related disorders have been classically defined by a set of key pathological hallmarks. Two these hallmarks, cell cycle dysregulation (CCD) nucleocytoplasmic transport (NCT) defects, long debated as being either causal or consequential in the pathology accelerated aging. Specifically, aberrant activation post-mitotic neurons has shown to trigger neuronal death pathways cellular senescence. Additionally, NCT observed be progressively...
Abstract Cellular senescence of brain cell types has become an increasingly important perspective for both aging and neurodegeneration, specifically in the context Parkinson’s Disease (PD). The characterization classical hallmarks is a widely debated topic, whereby which phenotype being investigated, such as type, inducing stressor, and/or model system, extremely aspect to consider when defining senescent cell. Here, we describe type-specific profile through investigation various canonical...
Human tibial muscular dystrophy and limb-girdle 2J are caused by mutations in the giant sarcomeric protein titin (TTN) adjacent to a binding site for muscle-specific protease calpain 3 (CAPN3). Muscular with myositis (mdm) is recessive mouse mutation severe progressive degeneration deletion N2A domain of (TTN-N2AΔ83), disrupting putative CAPN3. To determine whether mutant mdm mice misregulation CAPN3 activity, genetic crosses overexpressing transgenic (C3Tg) knockout (C3KO) were generated....
Rhabdomyosarcomas (RSCs) are skeletal muscle neoplasms found in humans and domestic mammals. The A/J inbred strain developed a high frequency (between 70–80%) of adult pleomorphic type (APT) RSC at >20 months age while BALB/cByJ also develop but less frequently. These invaded surrounding either the axial or proximal appendicular skeleton were characterized by cells with abundant eosinophilic cytoplasm, multiple nuclei, cross striations. diagnosis was confirmed detection alpha-sarcomeric...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive paralysis and death within 2–5 years after diagnosis. Sporadic cases (SALS) comprise approximately 90% of with the remaining 10% familial (FALS) caused by mutations in 27 genes. The vast heterogeneity seen age location disease onset, rate progression, duration has been linked genetic environmental influences both SALS FALS cases. Increased ALS incidence clusters Guam, southern France, Maryland have...
Pathological disruption of Nucleocytoplasmic Transport (NCT), such as the mis-localization nuclear pore complex proteins (Nups), transport receptors, Ran-GTPase, and RanGAP1, are seen in both animal models familial sporadic forms amyotrophic lateral sclerosis (ALS), frontal temporal dementia lobar degeneration (FTD\FTLD), Alzheimer's Related Dementias (AD/ADRD). However, question whether these alterations represent a primary cause, or downstream consequence disease is unclear, what upstream...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting motor neurons in the central nervous system. Although most cases of ALS are sporadic, about 5–10% familial (FALS) with approximately 20% FALS caused by mutations Cu/Zn superoxide dismutase (SOD1) gene. We have reported that hSOD1-G93A transgenic mice modeling this show more severe phenotype when transgene bred on pure SJL background and milder B6 these differences link to region mouse Chromosome 17.To...
Congenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. The observation of megamitochondria in skeletal biopsies exclusive to this type MD. disease caused loss function mutations the choline kinase beta (CHKB) gene which results dysfunction Kennedy pathway for synthesis phosphatidylcholine. We have previously reported a rostrocaudal MD (rmd) mouse deletion Chkb resulting MDCMC-like phenotype,...
AbstractAmyotrophic lateral sclerosis is a late-onset degenerative disease affecting motor neurons in the spinal cord, brainstem, and cortex. There great variation expression of ALS symptoms even between siblings who both carry same Cu/Zn superoxide dismutase (SOD1) mutations. One important use transgenic mouse models SOD1-ALS study genetic influences on severity. We utilized multiple inbred strains containing SOD1-G93A transgene to demonstrate major quantitative trait locus (QTL) chromosome...