- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Pluripotent Stem Cells Research
- Lysosomal Storage Disorders Research
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Neurological disorders and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Memory and Neural Mechanisms
- Genetic Neurodegenerative Diseases
- Nerve injury and regeneration
- Mesenchymal stem cell research
- Mitochondrial Function and Pathology
- Immunotherapy and Immune Responses
- Neuroscience and Neural Engineering
- Anesthesia and Neurotoxicity Research
- Parkinson's Disease Mechanisms and Treatments
- Toxin Mechanisms and Immunotoxins
- Traumatic Brain Injury and Neurovascular Disturbances
- Cell Adhesion Molecules Research
- Glioma Diagnosis and Treatment
- Transcranial Magnetic Stimulation Studies
- S100 Proteins and Annexins
- Cancer Research and Treatments
University of Minnesota
2016-2025
University of Minnesota Medical Center
2011-2025
University of Minnesota System
2003-2025
Twin Cities Orthopedics
2008-2024
StemCells (United States)
2019
Neurological Surgery
2019
University of California, San Francisco
2019
Boston University
2018
HiFiBiO Therapeutics (France)
2012-2015
Foundation for the National Institutes of Health
2012
Trinucleotide expansions cause disease by both protein- and RNA-mediated mechanisms. Unexpectedly, we discovered that CAG expansion constructs express homopolymeric polyglutamine, polyalanine, polyserine proteins in the absence of an ATG start codon. This repeat-associated non-ATG translation (RAN translation) occurs across long, hairpin-forming repeats transfected cells or when are integrated into genome lentiviral-transduced brains. Additionally, show RAN human spinocerebellar ataxia type...
Huntington's disease (HD) is an untreatable neurological disorder caused by selective and progressive degeneration of the caudate nucleus putamen basal ganglia. Although etiology HD pathology not fully understood, observed loss neuronal cells thought to occur primarily through apoptosis. Furthermore, there evidence in that cell death mediated mitochondrial pathways, deficits are commonly associated with HD. We have previously reported treatment tauroursodeoxycholic acid (TUDCA), a...
When expressed in heterologous cells, the viral FLIP protein (vFLIP) of Kaposi's-sarcoma-associated herpesvirus (KSHV) has been reported both to block Fas-mediated apoptosis and activate NF-kappaB activation pathway by interaction with IkappaB kinase (IKK). In a yeast-two-hybrid screen, we identified IKKgamma as an interacting partner vFLIP. We fragments mammalian cells bacteria, central CCR3/4 (amino acids 150-272) vFLIP binding region. To investigate proteins KSHV-infected primary effusion...
Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, modulates cell death by interrupting classic pathways of apoptosis. Intracerebral hemorrhage (ICH) is a devastating acute neurological disorder, without effective treatment, in which significant loss neuronal cells thought to occur In this study, we evaluated whether TUDCA can reduce brain injury and improve function after ICH rats. Administration before or up 6 h stereotaxic collagenase injection into the striatum reduced lesion...
Abstract An efficient shim system and an optimized localization sequence were used to measure in vivo 1 H NMR spectra from cerebral cortex, hippocampus, striatum, cerebellum of C57BL/6 mice at 9.4 T. The combination automatic first‐ second‐order shimming (FASTMAP) with strong custom‐designed coils (shim strength up 0.04 mT/cm 2 ) was crucial achieve high spectral resolution (water line width 11–14 Hz). Requirements for strengths compensate field inhomogeneities the mouse brain T assessed....
Abstract Spontaneous mouse models of cancer show promise to more accurately recapitulate human disease and predict clinical efficacy. Transgenic mice or viral vectors have been required generate spontaneous glioma, a lethal brain tumor, because nonviral gene transfer is typically transient. To overcome this constraint, we used the Sleeping Beauty transposable element achieve chromosomal integration oncogenes into endogenous cells immunocompetent mice. Genetically engineered, tumors were...
Introduction French bulldogs are one of the most popular dog breeds in United States and also among with highest risk for developing high-grade glioma (HGG). With limited treatment options high translational value studying canine HGG to advance understanding human glioblastoma (GB), a variety novel have been investigated. In other forms cancer, immunotherapy has shown promising results, garnering interest HGG. Yet, when an immunotherapy-based clinical trial was conducted, marked survival...
Abstract Background Several canine breeds, including boxers, Boston terriers, and French bulldogs, belong to the same phylogenetic clade have a higher risk for high-grade oligodendroglioma (HGO) than general population. Despite their shared increased HGO, bulldogs treated with immunotherapy experienced worse survival outcomes compared boxers terriers. We hypothesized that bulldog HGO transcriptome differs from those of which might account disparity in survival. performed RNA sequencing on...
Umbilical cord blood (UCB) is a rich source of hematopoetic stem cells (HSCs). We have isolated novel cell line population from human UCB that exhibit properties self-renewal, but do not cell-surface markers are typically found on HSCs. Analysis transcripts revealed these express transcription factors Oct-4, Rex-1, and Sox-2 expressed by cells. refer to as nonhematopoietic umbilical (nh-UCBSCs). Previous studies shown the intravenous infusion UCBCs can ameliorate neurological deficits...
Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, is strong modulator of apoptosis in both hepatic and nonhepatic cells, appears to function by inhibiting mitochondrial membrane perturbation. Excitotoxicity, metabolic compromise, oxidative stress are major determinants cell death after brain ischemia-reperfusion injury. However, some neurons undergo delayed that characteristic apoptosis. Therefore, the authors examined whether TUDCA could reduce injury associated with acute stroke...
Glioblastoma is a fatal brain tumor that becomes highly vascularized by secreting proangiogenic factors and depends on continued angiogenesis to increase in size. Consequently, successful antiangiogenic therapy should provide long-term inhibition of tumor-induced angiogenesis, suggesting gene transfer as therapeutic strategy. In this study soluble vascular endothelial growth factor receptor (sFlt-1) an angiostatin-endostatin fusion (statin-AE) were codelivered human glioblastoma xenografts...
A bstract : Umbilical cord blood is a rich source of hematopoietic stem cells. It routinely used for transplantation to repopulate cells the immune system. Recent studies, however, have demonstrated that intravenous infusions umbilical can ameliorate neurologic deficits associated with ischemic brain injury in rodents. Moreover, infused penetrate into parenchyma and adopt phenotypic characteristics typical neural In present study we tested hypothesis administration also diminish caused by...
Abstract The neurochemical profile of the striatum R6/2 Huntington’s disease mice was examined at different stages pathogenesis using in vivo 1 H NMR spectroscopy 9.4 T. Between 8 and 12 weeks, exhibited distinct changes a set 17 quantifiable metabolites compared with littermate controls. Concentrations creatine, glycerophosphorylcholine, glutamine glutathione increased N ‐acetylaspartate decreased weeks. By concentrations phosphocreatine, taurine, ascorbate, glutamate, myo ‐inositol...
Objective: Amyotrophic lateral sclerosis is a progressive degenerative disease, which typically leads to death in 3 5 years. Neuronal cell offers potential target for therapeutic intervention. Ursodeoxycholic acid cytoprotective, endogenous bile that has been shown be neuroprotective experimental Huntington and Alzheimer diseases, retinal degeneration, ischemic hemorrhagic stroke. The objective of this research was study the safety tolerability ursodeoxycholic amyotrophic document effective...
The concept of cancer stem cells suggests that there are malignant stem-like within a tumor responsible for renewal and resistance to cytotoxic therapies. Studies have identified glioma extrude Hoechst 33342 dye, representing double-negative "side population" (SP) thought be selectively resistant drug therapy. A CD133+ cell-like subpopulation has been isolated from human was enriched tumor-initiating cells. It is unknown whether with similar phenotype persist in established cell lines, or if...