A5028912017- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Cholinesterase and Neurodegenerative Diseases
- Prion Diseases and Protein Misfolding
- Nuclear Receptors and Signaling
- Nerve injury and regeneration
- RNA regulation and disease
- Neurological disorders and treatments
- Botulinum Toxin and Related Neurological Disorders
- RNA modifications and cancer
- S100 Proteins and Annexins
- Traumatic Brain Injury and Neurovascular Disturbances
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Dementia and Cognitive Impairment Research
- Advanced Neuroimaging Techniques and Applications
- Microtubule and mitosis dynamics
- Neurological diseases and metabolism
- Virus-based gene therapy research
- Epigenetics and DNA Methylation
- Forensic Toxicology and Drug Analysis
- Traumatic Brain Injury Research
Michigan State University
2016-2025
Michigan United
2025
Trinity Health Grand Rapids
2015-2023
Grand Rapids Community College
2016-2021
University of Utah
2016
VA Boston Healthcare System
2015
Boston University
2015
Urology of Virginia
2011
Northwestern University
2009-2011
Marine Biological Laboratory
2011
Neurofibrillary tangles, composed of insoluble aggregates the microtubule-associated protein Tau, are a pathological hallmark Alzheimer disease (AD) and other tauopathies. However, recent evidence indicates that neuronal dysfunction precedes formation these fibrillar deposits, suggesting earlier prefibrillar Tau may be neurotoxic. To determine composition aggregates, we have employed photochemical cross-linking technique to examine intermolecular interactions full-length in vitro. Using this...
Formation of membrane-less organelles via liquid-liquid phase separation is one way cells meet the biological requirement for spatiotemporal regulation cellular components and reactions. Recently, tau, a protein known its involvement in Alzheimer's disease other tauopathies, was found to undergo making it several proteins associated with neurodegenerative diseases do so. Here, we demonstrate that tau forms dynamic liquid droplets vitro at physiological levels upon molecular crowding buffers...
Aggregated filamentous forms of hyperphosphorylated tau (a microtubule-associated protein) represent pathological hallmarks Alzheimer9s disease (AD) and other tauopathies. While axonal transport dysfunction is thought to a primary pathogenic factor in AD neurodegenerative diseases, the direct molecular link between deficits remain unclear. Recently, we demonstrated that filamentous, but not soluble, wild-type inhibit anterograde, kinesin-based fast (FAT) by activating protein phosphatase 1...
Abstract Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer’s disease (AD). The prevailing hypothesis on the etiopathogenesis is that oAβ initiates pathology slowly spreads throughout medial temporal cortex neocortices independently Aβ, eventually leading memory loss. Here we show brief exposure extracellular recombinant human oligomers (oTau), but not monomers, produces an impairment long-term potentiation (LTP)...
Converging evidence suggests a role for microglia-mediated neuroinflammation in Parkinson's disease (PD). Animal models of PD can serve as platform to investigate the degeneration PD. However, due features previously available models, interpretations contributor or consequence neurodegeneration have remained elusive. In present study, we investigated temporal relationship model synucleinopathy following intrastriatal injection pre-formed alpha-synuclein fibrils (α-syn PFFS). Male Fischer 344...
Significance Phase separation of proteins is increasingly thought to play a fundamental role in biological processes. Recent studies show that tau protein phase separates, but the significance unknown since artificial crowding agents are typically used and resulting not toxic. We now demonstrate TIA1 potentiates RNA-mediated tau, thereby enabling process occurs at physiological concentrations also directs formation biologically active, highly neurotoxic oligomeric tau. Coordinated...
Post-mortem investigations of human Alzheimer's disease (AD) have largely failed to provide unequivocal evidence in support the original amyloid cascade hypothesis, which postulated deposition β-amyloid (Aβ) aggregates be cause a demented state as well inductive tau neurofibrillary tangles (NFTs). Conflicting suggests, however, that Aβ plaques and NFTs, albeit lesser extent, are present substantial subset non-demented individuals. Hence, range soluble species has more recently been...
In situ hybridization (ISH) is an extremely useful tool for localizing gene expression and changes in to specific cell populations tissue samples across numerous research fields. Typically, a group will put forth significant effort design, generate, validate then utilize probes thin or ultrathin paraffin embedded sections. While combining ISH IHC established technique, the combination of RNAscope ISH, commercially available assay with single transcript sensitivity, thick free-floating...
Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest tau oligomer formation induces neurotoxicity and oligomer-mediated involves induction axonal dysfunction through exposure an N-terminal motif tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 occurs early correlates with cognitive decline patients Alzheimer disease (AD). We performed...
Animal models that accurately recapitulate the accumulation of alpha-synuclein (α-syn) inclusions, progressive neurodegeneration nigrostriatal system and motor deficits can be useful tools for Parkinson's disease (PD) research. The preformed fibril (PFF) synucleinopathy model in rodents generally displays these PD-relevant features, however, magnitude predictability events is far from established. We therefore sought to optimize α-syn degeneration, understand time course both. Rats were...
Abstract Tau oligomers (oTau) are thought to precede neurofibrillary tangle formation and likely represent one of the toxic species in disease. This study addresses whether mitochondrial reactive oxygen (ROS) contribute tau oligomer accumulation. First, we determined elevated oxidative stress correlates with aggregation brain platelets human Alzheimer’s disease (AD) patient, tauopathy mice, primary cortical neurons from mice trans-mitochondrial ‘cybrid’ (cytoplasmic hybrid) neuronal cells,...
Aggregation of the protein tau defines tauopathies, which include Alzheimer's disease and frontotemporal dementia. Specific neuronal subtypes are selectively vulnerable to aggregation subsequent dysfunction death, but underlying mechanisms unknown. To systematically uncover cellular factors controlling accumulation aggregates in human neurons, we conducted a genome-wide CRISPRi-based modifier screen iPSC-derived neurons. The uncovered expected pathways, including autophagy, also unexpected...