A5028761898- Inflammatory mediators and NSAID effects
- Radiopharmaceutical Chemistry and Applications
- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
- Estrogen and related hormone effects
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- S100 Proteins and Annexins
- Bioinformatics and Genomic Networks
- Eicosanoids and Hypertension Pharmacology
- Neuropeptides and Animal Physiology
- Machine Learning in Bioinformatics
- Mitochondrial Function and Pathology
- Immune Response and Inflammation
- Protein Tyrosine Phosphatases
- Synthesis and Biological Evaluation
- Biological Research and Disease Studies
- Adenosine and Purinergic Signaling
- Biotin and Related Studies
- Cholinesterase and Neurodegenerative Diseases
- Ion channel regulation and function
- RNA modifications and cancer
- Phosphodiesterase function and regulation
- Medical Imaging Techniques and Applications
- Glycosylation and Glycoproteins Research
National Institute of Mental Health
2020-2025
National Institutes of Health
2020-2023
Mayo Clinic in Florida
2014-2015
Medical University of Silesia
2015
WinnMed
2014
Mayo Clinic
2014
Jacksonville College
2014
Cyclooxygenase-2 (COX-2) is present in a healthy brain at low densities but can be markedly upregulated by excitatory input and inflammogens. This study evaluated the sensitivity of PET radioligand [<sup>11</sup>C]-6-methoxy-2-(4-(methylsulfonyl)phenyl)-<i>N</i>-(thiophen-2-ylmethyl)pyrimidin-4-amine ([<sup>11</sup>C]MC1) to detect COX-2 density human brain. <b>Methods:</b> The specificity [<sup>11</sup>C]MC1 was confirmed using lipopolysaccharide-injected rats transgenic mice expressing...
To investigate the top late-onset Alzheimer disease (LOAD) risk loci detected or confirmed by International Genomics of Alzheimer's Project for association with brain gene expression levels to identify variants that influence (AD) through regulation.Expression from cerebellum (CER) and temporal cortex (TCX) were obtained using Illumina whole-genome cDNA-mediated annealing, selection, extension, ligation assay (WG-DASL) ∼400 autopsied patients (∼200 AD ∼200 non-AD pathologies). We tested 12...
Previous work found that [ 11 C]deschloroclozapine ([ C]DCZ) is superior to C]clozapine C]CLZ) for imaging Designer Receptors Exclusively Activated by Drugs (DREADDs). This study used PET quantitatively and separately measure the signal from transfected receptors, endogenous receptors/targets, non-displaceable binding in other brain regions better understand this superiority. A genetically-modified muscarinic type-4 human receptor (hM 4 Di) was injected into right amygdala of a male rhesus...
Previous studies found that [18F]LSN3316612 was a promising positron emission tomography (PET) radioligand for imaging O-GlcNAcase in nonhuman primates and human volunteers. This study sought to further evaluate the suitability of clinical research.Kinetic evaluation conducted combined set baseline brain scans from 17 healthy volunteers test-retest 10 these volunteers; another 6 had whole-body measure radiation exposure body organs. Total distribution volume (VT) estimates were compared one-...
Translocator protein 18 kDa (TSPO) is a biomarker of neuroinflammation. [
Cyclooxygenase-1 (COX-1) and its isozyme COX-2 are key enzymes in the syntheses of prostanoids. Imaging COX-1 selective radioligands with positron emission tomography (PET) may clarify how these involved inflammatory conditions assist discovery improved anti-inflammatory drugs. We have previously labeled high-affinity ligand, 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole (PS13), carbon-11 (t1/2 = 20.4 min). This radioligand ([11C]PS13) has been successful for PET...
We aimed to develop radioligands for PET imaging of brain phosphodiesterase subtype 4D (PDE4D), a potential target developing cognition enhancing or antidepressive drugs. Exploration several chemical series gave four leads with high PDE4D inhibitory potency and selectivity, optimal lipophilicity, good uptake. These featured alkoxypyridinyl cores. They were successfully labeled carbon-11 (
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Both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) convert arachidonic acid to prostaglandin H<sub>2</sub>, which has proinflammatory effects. The recently developed PET radioligand <sup>11</sup>C-PS13 excellent in vivo selectivity for COX-1 over COX-2 in nonhuman primates. This study sought evaluate the of binding humans assess utility measure potency nonsteroidal antiinflammatory drugs. <b>Methods:</b> Baseline whole-body scans were obtained 26 healthy volunteers, followed by...
OBJECTIVE:To investigate transcriptional regulation of late-onset Alzheimer’s disease (LOAD) GWAS risk loci genes in the human brain. BACKGROUND:We previously identified genetic associations brain levels at LOAD ABCA7 , BIN1, CLU, CR1 and MS4A4A with cisSNPs, including some top AD variants. Recently, 11 additional were through a large meta-analysis multiple GWAS. In this study, our first aim is to association these novel cis SNPs. Our second evaluate potential role alternative splicing gene...
We previously identified genetic associations with brain levels of genes at the late-onset Alzheimer's disease (LOAD) risk GWAS loci ABCA7, BIN1, CLU, CR1 and MS4A4A cis SNPs, including some top AD variants. further investigated association CLU locus variants long (CLU1) short (CLU2) isoforms determined that these two have opposite direction association. These results highlight importance evaluating gene expression for specific isoforms. In this study, we evaluate 20 LOAD from large...
OBJECTIVE:To investigate transcriptional regulation of late-onset Alzheimer's disease (LOAD) GWAS risk loci genes in the human brain. BACKGROUND:We previously identified genetic associations brain levels at LOAD ABCA7, BIN1, CLU, CR1 and MS4A4A with cisSNPs, including some top AD variants. Recently, 11 additional were through a large meta-analysis multiple GWAS. In this study, our first aim is to association these novel cisSNPs. Our second evaluate potential role alternative splicing gene...
Abstract Introduction We recently reported 11 C-NR2B-SMe ([ S - methyl C]( R,S )-7-thiomethoxy-3-(4-(4-methyl-phenyl)butyl)-2,3,4,5-tetrahydro-1 H -benzo[ d ]azepin-1-ol) and its enantiomers as candidate radioligands for imaging the GluN2B subunit within rat N -methyl-D-aspartate receptors. However, these gave unexpectedly high displaceable binding in cerebellum, possibly due to cross-reactivity with sigma-1 (σ1) This study investigated C-labeled of a close analogue (7-methoxy-3-(4-( p...
Abstract Purpose : 18 F-SF51 was previously found to have high binding affinity and selectivity for 18kDa translocator protein (TSPO) in mouse brain. This study sought further evaluate the suitability of absolute quantification TSPO monkey Methods: Positron emission tomography (PET) imaging performed brain (n=3) at baseline after pre-blockade with ligands PK11195 PBR28. calculated as total distribution volume corrected free parent fraction plasma ( V T / f P ) using a two-tissue compartment...
Abstract We recently reported 11 C-NR2B-SMe ([ S - methyl C]( R,S )-7-thiomethoxy-3-(4-(4-methyl-phenyl)butyl)-2,3,4,5-tetrahydro-1 H -benzo[ d ]azepin-1-ol) and its enantiomers as candidate radioligands for imaging the GluN2B subunit within rat N -methyl-D-aspartate receptors. However, these gave unexpectedly high displaceable binding in cerebellum, possibly due to cross-reactivity with sigma-1 (σ1) This study investigated C-labeled of a close analogue (7-methoxy-3-(4-( p...