A5103363656- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Hereditary Neurological Disorders
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Glioma Diagnosis and Treatment
- RNA regulation and disease
- Multiple Sclerosis Research Studies
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
- MicroRNA in disease regulation
- Signaling Pathways in Disease
- Alzheimer's disease research and treatments
- Virus-based gene therapy research
- Neurogenetic and Muscular Disorders Research
- Lysosomal Storage Disorders Research
- Peripheral Neuropathies and Disorders
- Pluripotent Stem Cells Research
- Peroxisome Proliferator-Activated Receptors
- Cytokine Signaling Pathways and Interactions
- Medical Imaging and Analysis
- Animal Genetics and Reproduction
- Immune Cell Function and Interaction
- interferon and immune responses
- Muscle Physiology and Disorders
Northwestern University
2016-2025
University of Chicago
2010-2023
SleepMed
2017
University of Illinois Chicago
2016
Jack Miller Center
2002-2010
Neurology, Inc
2007-2008
University of North Carolina at Chapel Hill
1993-2003
Center for Neurosciences
1996-2002
Institute of Molecular Biology and Biophysics
1994-2002
Tusculum College
2002
Mammalian sulfoglycolipids comprise two major members, sulfatide (HSO3-3-galactosylceramide) and seminolipid (HSO3-3-monogalactosylalkylacylglycerol). Sulfatide is a lipid component of the myelin sheath serves as epitope for well known oligodendrocyte-marker antibody O4. Seminolipid synthesized in spermatocytes maintained subsequent germ cell stages. Both can be vitro by using isolated cerebroside sulfotransferase. To investigate physiological role to determine whether are biosynthesized...
Abstract Summary: To explore the function of genes expressed by myelinating cells we have developed a model system that allows for inducible ablation predetermined in oligodendrocytes and Schwann cells. The Cre/loxP recombination provides opportunity to generate tissue‐specific somatic mutations mice. We used fusion protein between Cre recombinase mutated ligand‐binding domain human estrogen receptor (CreER T ) obtain inducible, site‐specific recombination. CreER expression was placed under...
Mice incapable of synthesizing the abundant galactolipids myelin exhibit disrupted paranodal axo-glial interactions in central and peripheral nervous systems. Using these mutants, we have analyzed role that play establishment axonal protein distribution region node Ranvier. Whereas clustering nodal proteins, sodium channels, ankyrinG, neurofascin was only slightly affected, potassium channels paranodin, proteins are normally concentrated regions juxtaposed to node, dramatically altered. The...
Myelinated axons are divided into four distinct regions: the node of Ranvier, paranode, juxtaparanode, and internode, each which is characterized by a specific set axonal proteins. Voltage-gated Na<sup>+</sup> channels clustered at high densities nodes, whereas shaker-type K<sup>+</sup> concentrated juxtaparanodal regions. These separated paranodal regions, where septate-like junctions formed between axon myelinating glial cells. Although oligodendrocytes myelin sheaths believed to play an...
The vertebrate myelin sheath is greatly enriched in the galactolipids galactocerebroside (GalC) and sulfatide. Mice with a disruption gene that encodes biosynthetic enzyme UDP-galactose:ceramide galactosyl transferase (CGT) are incapable of synthesizing these lipids yet form sheaths exhibit major minor dense lines spacing comparable to controls. These CGT mutant mice severe tremor accompanied by hindlimb paralysis. Furthermore, electrophysiological studies reveal nerve conduction deficits...
Interferon-γ (IFN-γ) is believed to play a deleterious role in the immune-mediated demyelinating disorder multiple sclerosis. Here we have exploited transgenic mice that ectopically express IFN-γ temporally controlled manner CNS specifically study its effects on remyelination cuprizone-induced demyelination model and experimental autoimmune encephalomyelitis (EAE), an animal of delivery severely suppressed both models impaired clinical recovery experiencing EAE. These observations correlated...
I*nterferon-γ (IFN-γ) is believed to contribute immune-mediated demyelinating disorders by targeting the myelin-producing oligodendrocyte, a cell known be highly sensitive disruption of protein synthesis and perturbation secretory pathway. We found that apoptosis induced IFN-γ in cultured rat oligodendrocytes was associated with endoplasmic reticulum (ER) stress. ER stress also accompanied oligodendrocyte hypomyelination transgenic mice inappropriately expressed central nervous system (CNS)....
In response to ER stress, the pancreatic endoplasmic reticulum kinase (PERK) coordinates an adaptive program known as integrated stress (ISR) by phosphorylating α subunit of eukaryotic translation initiation factor 2 (eIF2α). IFN-γ, which activates in oligodendrocytes, is believed play a critical role immune-mediated CNS disorder multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). Here we report that delivery IFN-γ before EAE onset ameliorated...
Mice heterozygous for the radiation-induced Sprawling (Swl) mutation display an early-onset sensory neuropathy with muscle spindle deficiency. The lack of H reflex despite normal motor nerve function in hindlimbs these mutants strongly suggests defective proprioception. Immunohistochemical analyses reveal that proprioceptive neurons are severely compromised lumbar dorsal root ganglia newborn Swl/+ mice, whereas neuron numbers remain unaltered even aged animals. We have used positional...
Mutant superoxide dismutase type 1 (MTSOD1) is thought to cause ∼20% of cases familial amyotrophic lateral sclerosis (FALS) because it misfolds and aggregates. Previous studies have shown that MTSOD1 accumulates inside the endoplasmic reticulum (ER) activates unfolded protein response (UPR), suggesting ER stress involved in pathogenesis FALS. We used a genetic approach investigate role UPR crossed G85RSOD1 transgenic mice with pancreatic kinase haploinsufficient (PERK+/−) obtain G85R/PERK+/−...
Oligodendrocytes (OLs) and myelin are critical for normal brain function have been implicated in neurodegeneration. Several lines of evidence including neuroimaging neuropathological data suggest that Alzheimer's disease (AD) may be associated with dysmyelination a breakdown OL-axon communication. In order to understand this phenomenon on molecular level, we systematically interrogated OL-enriched gene networks constructed from large-scale genomic, transcriptomic proteomic obtained human AD...
Abstract Background Genome-wide association studies have identified BIN1 within the second most significant susceptibility locus in late-onset Alzheimer’s disease (AD). undergoes complex alternative splicing to generate multiple isoforms with diverse functions cellular processes including endocytosis and membrane remodeling. An increase expression AD an interaction between Tau been reported. However, disparate descriptions of localization brain previously reported literature lack clarity on...
There is compelling evidence that oligodendrocyte apoptosis, in response to CNS inflammation, contributes significantly the development of demyelinating disorder multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Therefore, approaches designed protect oligodendrocytes would likely have therapeutic value. Activation pancreatic endoplasmic reticulum kinase (PERK) signaling (ER) stress increases cell survival under various cytotoxic conditions. Moreover,...