A5064959537- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Immune Response and Inflammation
- interferon and immune responses
- Immune Cell Function and Interaction
- Clusterin in disease pathology
- S100 Proteins and Annexins
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Inflammation biomarkers and pathways
- Bioinformatics and Genomic Networks
- Bacterial Infections and Vaccines
- Tryptophan and brain disorders
- Eating Disorders and Behaviors
- Immune responses and vaccinations
- Cerebrovascular and Carotid Artery Diseases
- Gut microbiota and health
- Autophagy in Disease and Therapy
- SARS-CoV-2 and COVID-19 Research
- Diet and metabolism studies
- Neuroendocrine regulation and behavior
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
Mayo Clinic in Florida
2014-2020
Jacksonville College
2014-2020
WinnMed
2014-2017
Mayo Clinic
2015
National Institutes of Health
2009-2011
National Institute of Neurological Disorders and Stroke
2010-2011
Scripps Research Institute
2008
Washington University in St. Louis
2004-2008
Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries re-ignited interest role neuroinflammation pathogenesis neurodegenerative diseases. TREM2 is highly microglia, resident immune central nervous system. Along with its adaptor protein, DAP12, regulates inflammatory...
The ingestion of a high-fat diet (HFD) and the resulting obese state can exert multitude stressors on individual including anxiety cognitive dysfunction. Though many studies have shown that exercise alleviate negative consequences HFD using metabolic readouts such as insulin glucose, paucity well-controlled rodent been published interactions with regard to behavioral outcomes. This is critical issue since some individuals assume HFD-induced problems dysfunction simply be exercised away. To...
Alzheimer's disease (AD) is an age-associated neurodegenerative characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Using this in models aging, we revealed common set alterations identified central APOE-driven network converged on CCL3 CCL4 across all conditions. Notably, aged females demonstrated significant exacerbation...
Obesity induces a low-grade inflammatory state and has been associated with behavioral cognitive alterations. Importantly, maternal environmental insults can adversely impact subsequent offspring behavior have linked neurodevelopmental disorders such as autism spectrum disorder (ASD) attention deficit hyperactivity (AHDH). It is unknown if obesity significantly alters sociability, key ASD feature, altering diet will provide an efficacious intervention paradigm for deficits. Here we...
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) peptide deposition in brain parenchyma as plaques and cerebral blood vessels amyloid angiopathy (CAA). CAA leads to several clinical complications, including intracerebral hemorrhage. The underlying molecular mechanisms that regulate plaque the vast majority of sporadic AD patients remain unclear. clusterin (CLU) gene genetically associated with CLU has been shown alter aggregation, toxicity, blood-brain barrier transport Aβ,...
Background The constellation of human inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, which both display a wide spectrum in the severity pathology. One theory is that multiple genetic hits to host immune system may contribute susceptibility IBD. However, experimental proof this concept still lacking. Several mouse models each recapitulate some aspects IBD have utilized single gene defect induce colitis. none produced pathology clearly distinguishable as...
Abstract Introduction The cytoprotective PTEN‐induced kinase 1 (PINK1)‐parkin RBR E3 ubiquitin protein ligase (PRKN) pathway selectively labels damaged mitochondria with phosphorylated (pS65‐Ub) for their autophagic removal (mitophagy). Because dysfunctions of and degradation pathways are early features Alzheimer's disease (AD), mitophagy impairments may contribute to the pathogenesis. Methods Morphology, levels, distribution tag pS65‐Ub were evaluated by biochemical analyses combined tissue...
Aberrant tau protein accumulation drives neurofibrillary tangle (NFT) formation in several neurodegenerative diseases. Currently, efforts to elucidate pathogenic mechanisms and assess the efficacy of therapeutic targets are limited by constraints existing models tauopathy. In order generate a more versatile mouse model tauopathy, somatic brain transgenesis was utilized deliver adeno-associated virus serotype 1 (AAV1) encoding human mutant P301L-tau compared with GFP control. At 6 months age,...
It is clear that innate immune system status altered in numerous neurodegenerative diseases. Human genetic studies have demonstrated triggering receptor expressed myeloid cells 2 (TREM2) coding variants a strong association with Alzheimer's disease (AD) and other To more thoroughly understand the impact of TREM2 vivo, we studied behavioral cognitive functions wild-type (WT) Trem2−/− (KO) mice during basal conditions brain function context stimulation peripherally administered...
Accumulation of amyloid-β (Aβ) peptide in the brain is a pathological hallmark Alzheimer's disease (AD). The clusterin (CLU) gene confers risk for AD and CLU highly upregulated patients, with common non-coding, protective variants associated increased expression. Although there strong evidence implicating amyloid metabolism, exact mechanism underlying involvement not fully understood or whether physiologic alterations levels would be protective.
The molecular chaperone Clusterin (CLU) impacts the amyloid pathway in Alzheimer's disease (AD) but its role tau pathology is unknown. We observed CLU co-localization with aggregates AD and primary tauopathies levels were upregulated response to accumulation. To further elucidate effect of on pathology, we utilized a gene delivery approach knock-out (CLU KO) mice drive expression bearing P301L mutation. found that loss was associated exacerbated anxiety-like behaviors our mouse model...
After virus infection, cytotoxic T lymphocytes (CTLs) divide rapidly to eradicate the pathogen and prevent establishment of persistence. The magnitude an antiviral CTL response is thought be controlled by initiation a cell cycle program within lymphoid tissues. However, it presently not known whether this division proceeds during migration or influenced locally at sites viral infection. We demonstrate that CTLs remain in while transiting infected Up one third virus-specific blood were found...
Although abundant genetic and biochemical evidence strongly links Clusterin (CLU) to Alzheimer disease (AD) pathogenesis, the receptor for CLU within adult brain is currently unknown. Using unbiased approaches, we identified Plexin A4 (PLXNA4) as a novel, high-affinity in brain. PLXNA4 protein expression was high with much lower levels peripheral organs. were significantly elevated cerebrospinal fluid (CSF) of Plxna4-/- mice and, humans, CSF also associated genotype. Human AD brains had...
Although IL-10 acts as an inhibitory cytokine for APC and CD4(+) T cell function, its effects on CD8(+) cells are unclear. Additionally, little is known about whether initial priming in the presence of can have long-lasting influence subsequent responses that occur absence cytokine. In present study, we clarified role during primary examined exposure to impacted secondary responses. To determine effect Ag-specific responses, peptide-pulsed IL-10R2(-/-) splenic dendritic were used prime from...
Peptide vaccination is an immunotherapeutic strategy being pursued as a method of enhancing Ag-specific antitumor responses. To date, most studies have focused on the use MHC class I-restricted peptides, and not shown correlation between CD8(+) T cell expansion generation protective immune We investigated effects CD4-directed peptide ability cells to mount responses in DUC18/CMS5 tumor model system. accomplish this, we extended amino acid sequence known DUC18 rejection epitope from CMS5...
Obesity induces a low-grade inflammatory state and has been associated with behavioral cognitive alterations. Importantly, maternal environmental insults can adversely impact subsequent offspring behavior have linked neurodevelopmental disorders such as autism spectrum disorder (ASD) attention deficit hyperactivity (AHDH). It is unknown if obesity significantly alters sociability, key ASD feature, altering diet will provide an efficacious intervention paradigm for deficits. Here we...
Abstract Microglia are the resident innate immune population of central nervous system that constantly survey and influence their local environment. Transcriptomic profiling has led to significant advances in our understanding microglia several disease states, but tissue dissociation purification is known lead cellular activation. Here we use RiboTag translational RNAseq demonstrate commonly used cell sorting methods a fundamental alteration microglial transcriptome, with transcripts can be...
Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) peptide deposition in brain parenchyma as plaques and cerebral blood vessels amyloid angiopathy (CAA). CAA leads to several clinical complications, including intracerebral hemorrhage. The underlying molecular mechanisms that regulate plaque the vast majority of sporadic AD patients remain unclear. clusterin (CLU) gene genetically associated with CLU has been shown alter aggregation, toxicity blood-brain barrier transport Aβ,...