A5081488726- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Opioid Use Disorder Treatment
- Immune Response and Inflammation
- Neurological Disease Mechanisms and Treatments
- Toxoplasma gondii Research Studies
- Autophagy in Disease and Therapy
- Retinoids in leukemia and cellular processes
- Cholesterol and Lipid Metabolism
- Polyomavirus and related diseases
- Nerve injury and regeneration
- Inflammation biomarkers and pathways
- Pharmaceutical Practices and Patient Outcomes
- Sphingolipid Metabolism and Signaling
- Plant Virus Research Studies
- Immune cells in cancer
- Tryptophan and brain disorders
- Mosquito-borne diseases and control
- Stress Responses and Cortisol
- Autism Spectrum Disorder Research
- Fatty Acid Research and Health
- Primary Care and Health Outcomes
- Cellular Mechanics and Interactions
- Axon Guidance and Neuronal Signaling
- Neuroblastoma Research and Treatments
Northeast Ohio Medical University
2020-2025
Case Western Reserve University
2007-2022
MetroHealth Medical Center
2022
University School
2007-2018
University of Cincinnati Medical Center
2004
Microglia are the brain's tissue macrophages and found in an activated state surrounding β-amyloid plaques Alzheimer's disease brain. interact with fibrillar (fAβ) through ensemble of surface receptors composed α 6 β 1 integrin, CD36, CD47, class A scavenger receptor. These act concert to initiate intracellular signaling cascades phenotypic activation these cells. However, it is unclear how engagement this receptor complex linked induction microglial phenotype. We report that response cells...
Alzheimer's disease (AD) is an age-dependent neurodegenerative that causes progressive cognitive impairment. The initiation and progression of AD has been linked to cholesterol metabolism inflammation, processes can be modulated by liver x receptors (LXRs). We show here endogenous LXR signaling impacts the development AD-related pathology. Genetic loss either Lxralpha or Lxrbeta in APP/PS1 transgenic mice results increased amyloid plaque load. LXRs regulate basal inducible expression key...
The R47H variant of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) confers greatly increased risk for Alzheimer's disease (AD), reflective a central role myeloid in neurodegeneration. Understanding how this AD promises to provide important insights into contribute pathogenesis and progression.In order investigate mechanism, CRISPR/Cas9 was used generate mouse model harboring one copy the single nucleotide polymorphism (SNP) encoding murine Trem2. TREM2 expression, cell responses...
Alzheimer's disease (AD) is a prominent neurodegenerative disorder characterized by deposition of β-amyloid (Aβ)-containing extracellular plaques, accompanied microglial-mediated inflammatory response, that leads to cognitive decline. Microglia perform many disease-modifying functions such as phagocytosis plaque compaction, and modulation inflammation through the secretion cytokines. are reliant upon colony-stimulating factor receptor-1 (CSF1R) activation for survival. In AD mouse models,...
Alzheimer's disease (AD) is characterized by the deposition of β-amyloid (Aβ)-containing plaques within brain that accompanied a robust microglial-mediated inflammatory response. This response reliant upon engagement innate immune signaling pathways involving toll-like receptors (TLRs). Studies assessing roles TLRs in AD pathogenesis have yielded conflicting results. We assessed through genetic inactivation TLR2/4 coreceptor, CD14, transgenic murine model AD. Transgenic mice lacking CD14...
Alzheimer’s disease (AD) is accompanied by a robust inflammatory response mediated plaque-associated myeloid cells of the brain. These exhibit altered gene expression profiles and serve as barrier, preventing neuritic dystrophy. The origin these has been controversial therapeutic importance. Here, we genetically labeled different populations unequivocally demonstrated that in AD brain are derived exclusively from resident microglia, with no contribution circulating peripheral monocytes.
Autophagy degrades pathogens in vitro. The autophagy gene Atg5 has been reported to be required for IFN-γ-dependent host protection vivo. However, these protective effects occur independently of autophagosome formation. Thus, the vivo role classic conferred by adaptive immunity and how triggers are incompletely understood. Employing biochemical, genetic morphological studies, we found that CD40 upregulates molecule Beclin 1 microglia killing Toxoplasma gondii dependent on machinery. Infected...
Dementia is an umbrella term used to describe deterioration of cognitive function. It the seventh leading cause death and one major causes dependence among older people globally. Alzheimer's Disease (AD) contributes approximately 60-70% dementia cases characterized by accumulation amyloid plaques tau tangles in brain. Neuroinflammation now widely accepted as another disease hallmark, playing a role both response perpetuation processes. Microglia are brain-resident immune cells that initially...
Resident progenitor cells in mammalian skin generate new as a part of tissue homeostasis. We sought to identify the progenitors Merkel cells, unique cell type that plays critical roles mechanosensation. found some Atoh1-expressing hairy and whisker follicles are mitotically active at embryonic postnatal ages. Genetic fate-mapping revealed these give rise solely cells. Furthermore, selective ablation Atoh1(+) adult mice led permanent reduction numbers, demonstrating other stem populations...
Alzheimer's disease (AD) is a neurodegenerative disorder disproportionally affecting women with sex-specific manifestations and therapeutic responses. Microglial-mediated inflammation occurs in response to perpetuates processes, fundamental sex differences microglia may contribute these biases. Both chromosomes gonad-derived hormones shape immune responses, but their contribution immune-mediated mechanisms underlying the bias AD unclear. Crossing Four Core Genotype (FCG) model separate...
The extent to which the skin instructs peripheral somatosensory neuron maturation is unknown. We studied this question in Merkel cell–neurite complexes, where slowly adapting type I (SAI) neurons innervate skin-derived cells. Transgenic mice lacking cells had normal dorsal root ganglion (DRG) numbers, but fewer DRG expressed SAI markers TrkB, TrkC, and Ret. cell ablation also decreased downstream TrkB signaling DRGs, altered expression of genes associated with development function. Skin-...
Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by pathological hallmarks of beta-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Treatment remains clinical obstacle due to lack effective therapeutics. Agonists targeting nuclear receptors, such as bexarotene, reversed deficits regardless treatment duration age in murine models AD. While bexarotene demonstrated marked efficacy decreasing levels following short-term...
Research into Alzheimer's Disease (AD) describes a link between AD and the resident immune cells of brain, microglia. Further, this suspected is thought to have underlying sex effects, although mechanisms these effects are only just beginning be understood. Many insights result policies put in place by funding agencies such as National Institutes Health (NIH) consider biological variable (SABV) move towards precision medicine due continued lackluster therapeutic options. The purpose review...
Genetic variants in TREM2 have been associated with several neurodegenerative diseases. Recessive loss of function mutations results Nasu-Hakola disease, characterized by bone cysts and a non-AD dementia while the heterozygous R47H variant confers increased risk for late onset AD. Several groups postulated that is function. However, our previous study, we found complete deficiency an AD mouse model resulted significant attenuation AD-like pathology. It therefore becomes critical to determine...