A5049198562- Neurotransmitter Receptor Influence on Behavior
- Cannabis and Cannabinoid Research
- Epigenetics and DNA Methylation
- Forensic Toxicology and Drug Analysis
- Psychedelics and Drug Studies
- Cytokine Signaling Pathways and Interactions
- Connective tissue disorders research
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- interferon and immune responses
- Chemical synthesis and alkaloids
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Vitamin K Research Studies
- Neuroscience and Neuropharmacology Research
- Stress Responses and Cortisol
- Liver Disease Diagnosis and Treatment
- Pharmacological Receptor Mechanisms and Effects
- Cancer Genomics and Diagnostics
- Microbial metabolism and enzyme function
- Bone and Dental Protein Studies
- Plant-based Medicinal Research
- Biochemical Analysis and Sensing Techniques
- Lipid metabolism and biosynthesis
- Adipose Tissue and Metabolism
- Diet, Metabolism, and Disease
Washington University in St. Louis
2020-2024
Molecular Oncology (United States)
2021-2024
University of Arkansas for Medical Sciences
2009-2019
Hunter College
2010
Background K2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use which is often associated with clinical symptoms atypical marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent cannabinoid, structurally distinct from Δ9-THC, the main psychoactive ingredient in marijuana. Since even subtle structural differences can lead to differential metabolism, formation novel, biologically active metabolites...
Drug-elicited head-twitch behavior is a useful model for studying hallucinogen activity at 5-HT<sub>2A</sub> receptors in the mouse. Chemically diverse compounds active this assay yield biphasic dose-effect curves, but there no compelling explanation “descending” portion of these functions. A set experiments was designed to test hypothesis that induction mediated by agonist actions receptors, whereas inhibition observed higher doses results from competing 5-HT<sub>2C</sub> receptors. The...
Collagen is a major component of the extracellular matrix and its integrity essential for connective tissue organ function. The importance proteins involved in intracellular collagen post-translational modification, folding transport was recently highlighted from studies on recessive forms osteogenesis imperfecta (OI). Here we describe critical role SC65 (Synaptonemal Complex 65, P3H4), leprecan-family member, as part an endoplasmic reticulum (ER) complex with prolyl 3-hydroxylase 3. This...
Marijuana substitutes often contain blends of multiple psychoactive synthetic cannabinoids (SCBs), including the prevalent SCBs (1-pentyl-1H-indole-3-yl)-1-naphthalenyl-methanone (JWH-018) and (1-butyl-1H-indole-3-yl)-1-naphthalenyl-methanone (JWH-073). Because are frequently used in combinations, we hypothesized that coadministering induces synergistic drug-drug interactions. Drug-drug interactions between JWH-018 JWH-073 were investigated vivo for Δ(9)-tetrahydrocannabinol (Δ(9)-THC)-like...
Abstract Osteocytes are long‐lived, highly interconnected, terminally differentiated osteoblasts that reside within mineralized bone matrix. They constitute about 95% of adult cells and play important functions including in the regulation remodeling, phosphate homeostasis, mechanical stimuli sensing response. However, role osteocytes pathogenesis congenital diseases abnormal matrix is poorly understood. This study characterized vivo transcriptional changes from Crtap KO oim/oim mouse models...
Osteogenesis imperfecta (OI) is characterized by osteopenia and bone fragility, OI patients during growth often exhibit high turnover with the net result of low mass. Recent evidence shows that osteocytes significantly affect remodeling under physiological pathological conditions through production osteoclastogenic cytokines. The receptor activator nuclear factor kappa-B ligand (RANKL) produced for example, a critical mediator loss caused ovariectomy, low-calcium diet, unloading...
The Leprecan protein family which includes the prolyl 3-hydroxylase enzymes (P3H1, P3H2, and P3H3), closely related cartilage-associated (CRTAP), SC65 (Synaptonemal complex 65, aka P3H4, LEPREL4), is involved in post-translational modification of fibrillar collagens. Mutations CRTAP, P3H1 P3H2 cause human genetic diseases. We recently showed that forms a stable endoplasmic reticulum with P3H3 lysyl hydroxylase 1 loss this leads to defective collagen hydroxylation causes low bone mass skin...
Epigenetic modifications to DNA and chromatin control oncogenic tumor suppressive mechanisms in melanoma. EZH2, the catalytic component of Polycomb repressive complex 2 (PRC2), which mediates methylation lysine 27 on histone 3 (H3K27me3), can regulate both melanoma initiation progression. We previously found that mutant
Mutations in the histone methyltransferase EZH2, particularly Y641 hotspot mutation, have been implicated hematologic malignancies, yet effect of timing and cellular context on their oncogenic potential has remained unknown. In this study, we utilized a conditional allele with tissue-specific Cre drivers to investigate effects Ezh2Y641F mutations at various stages development, focus hematopoietic system. We found that ubiquitous heterozygous expression birth, or mesenchymal stem cells, led...
Aminoalkylindole cannabinioids have recently emerged as drugs of abuse in the US and worldwide. Perhaps most common such compound present commercial K2/Spice blends is JWH‐018. The effects these smoking are often more intense than those marijuana, likely because aminoalkylindoles higher affinity for efficacy at CB1 cannabinoid receptors. Indeed, adverse reactions including agitation, paranoia, tachycardia, seizure, even death been reported following exposure to K2 products containing To...
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Designer stimulants are rapidly emerging as drugs of abuse. Marketed “bath salts” or “plant food,” these commercial products typically contain cathinone analogues such 3,4‐methylenedioxypyrovalerone (MDPV), but little is known about the underlying in vivo pharmacology drugs. In studies, we assessed effects MDPV on core temperature and locomotor activity mice a function ambient temperature. Further studies extended findings by depleting serotonin (5‐ HT) catecholamines (DA NE) order to gauge...
Abstract EZH2 (Enhancer of Zeste Homolog 2) is the catalytic component Polycomb Repressive Complex group 2 (PRC2), which establishes repressive epigenetic mark histone 3 lysine 27 trimethylation (H3K27me3), resulting in silencing gene expression. was originally identified as a tumor suppressor since loss-of-function events were observed myelodysplastic syndrome, acute myeloid, and T-cell leukemias. However, next-generation sequencing recurrent activating point mutations at tyrosine residue...
ABSTRACT One of the most frequently genetically altered chromatin modifiers in melanoma is Enhancer Zeste Homolog 2 ( EZH2 ), catalytic component Polycomb Repressive Complex (PRC2), which methylates lysine 27 on histone 3 (H3K27me3), a mark associated with transcriptional repression. Genetic alterations include amplifications and activating point mutations at tyrosine 641 (Y641). The oncogenic role has previously been identified; however, its downstream mechanisms remain underexplored. We...
Abstract Cancer genetic sequencing studies have identified systematic alterations of epigenetic and chromatin modifiers in most cancers, consistent with the fact that modifiers, such as Polycomb Repressive Complex 2 (PRC2), regulate expression tumor suppressors. In melanoma, 10% patients exhibit amplifications or point mutations EZH2, enzymatic subunit PRC2; however, oncogenic mechanisms EZH2 melanoma remain elusive. Previously, we observed Ezh2-Y641F cells resulted upregulation IFN-related...