A5062036720- Cannabis and Cannabinoid Research
- Metabolomics and Mass Spectrometry Studies
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Cancer, Stress, Anesthesia, and Immune Response
- GABA and Rice Research
- Melanoma and MAPK Pathways
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Mass Spectrometry Techniques and Applications
- Acute Lymphoblastic Leukemia research
- PI3K/AKT/mTOR signaling in cancer
- Acute Myeloid Leukemia Research
- DNA Repair Mechanisms
- Neuroscience of respiration and sleep
- Adipose Tissue and Metabolism
- Cancer Cells and Metastasis
- Nanoplatforms for cancer theranostics
- Healthcare cost, quality, practices
- Cytokine Signaling Pathways and Interactions
- Pluripotent Stem Cells Research
- Zebrafish Biomedical Research Applications
- Atrial Fibrillation Management and Outcomes
Banner - University Medical Center Tucson
2024
University of Washington
2019-2024
Seattle University
2022-2023
University of California, Merced
2017-2019
St. George's University
2019
Stanford University
2010
Institute of Neurobiology
2010
Degenerating myelin inhibits axon regeneration and is rapidly cleared after peripheral (PNS) but not central nervous system (CNS) injury. To better understand mechanisms underlying rapid PNS clearance, we tested the potential role of humoral immune system. Here, show that endogenous antibodies are required for robust clearance regeneration. B-cell knockout JHD mice display a significant delay in macrophage influx, Rapid debris restored mutant by passive transfer from naïve WT or an anti-PNS...
Among breast cancers, the triple-negative cancer (TNBC) subtype has worst prognosis with no approved targeted therapies and only standard chemotherapy as backbone of systemic therapy. Unique metabolic changes in progression provide innovative therapeutic opportunities. The receptor tyrosine kinases (RTKs) epidermal growth factor (EGFR), MET are highly expressed TNBC, making both promising targets. RTK signaling profoundly alters cellular metabolism by increasing glucose consumption...
Abstract Aberrant glutamatergic signaling has been implicated in altered metabolic activity many cancer types, including malignant melanoma. Previously, we have illustrated the role of metabotropic glutamate receptor 1 (GRM1) neoplastic transformation melanocytes vitro and spontaneous metastatic melanoma vivo. In this study, showed that autocrine stimulation constitutively activates GRM1 its downstream mitogenic signaling. GRM1-activated (GRM1+) melanomas exhibited significantly increased...
Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, anti-tumorigenic effect and clinical benefit are only transient, tumors prone to treatment resistance relapse. To elucidate mechanistic insights into drug resistance, we have established an vitro cellular model of MAPK inhibitor malignant melanoma. The evolved response dosage inhibitor, vemurafenib, PLX4032. We conducted transcriptomic...
Introduction The high prevalence and severe symptoms of migraines in humans emphasizes the need to identify underlying mechanisms that can be targeted for therapeutic benefit. Clinical Endocannabinoid Deficiency (CED) posits reduced endocannabinoid tone may contribute migraine development other neuropathic pain conditions. While strategies increase levels n-arachidonoylethanolamide have been tested, few studies investigated targeting more abundant endocannabinoid, 2-arachidonoylgycerol, as...
The endocannabinoid 2-arachidonoylglycerol (2-AG) is involved in neuronal differentiation. This study aimed to identify the biosynthetic enzymes responsible for 2-AG production during retinoic acid (RA)-induced neurite outgrowth of Neuro-2a cells. First, we confirmed that RA stimulation cells increases and outgrowth. diacylglycerol lipase (DAGL) inhibitor DH376 blocked reduced Surprisingly, CRISPR/Cas9-mediated knockdown DAGLα DAGLβ did not reduce levels, suggesting another enzyme capable...
Background and Purpose Neurotransmission neuroinflammation are controlled by local increases in both extracellular ATP the endocannabinoid 2‐arachidonoyl glycerol (2‐AG). While it is known that stimulates 2‐AG production cells culture, dynamics molecular mechanisms underlie this response remain poorly understood. Detection of real‐time changes eCB levels with genetically encoded sensor, GRAB eCB2.0 , can address shortfall. Experimental Approach arachidonoylethanolamide (AEA) Neuro2a (N2a)...
Vascular progenitor cells (VPCs) derived from embryonic stem (ESCs) are a valuable source for cell- and tissue-based therapeutic strategies. During the optimization of endothelial cell (EC) inductions mouse ESCs using our staged chemically-defined induction methods, we found that seeding density but not VEGF treatment between 10 ng/mL 40 was significant variable directing into FLK1+ VPCs during stage 1 induction. Here, examine potential contributions cell-to-cell signaling or cellular...
Abstract Background The impact of chronic kidney disease (CKD) on atrial fibrillation outcomes (AF) is not well understood. Methods We conducted analyses comorbid AF and CKD related death in the United States from 1999 to 2020 using descriptive epidemiology. Results Age‐adjusted mortality rates (AAMR) per 100,000 increased 0.39 1.65 2020. Non‐Hispanic populations (1.01) nonmetropolitan areas (1.08) had higher AAMRs compared Hispanic (0.62) metropolitan (0.97) areas. Midwestern (1.11) Western...
The endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamine (AEA), are produced by separate enzymatic pathways, activate cannabinoid (CB) receptors with distinct pharmacological profiles, differentially regulate pathophysiological processes. genetically encoded sensor, GRAB
We describe a set of benzisothiazolinone (BTZ) derivatives that are potent inhibitors monoacylglycerol lipase (MGL), the primary degrading enzyme for endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Structure–activity relationship studies evaluated various substitutions on nitrogen atom and benzene ring BTZ nucleus. Optimized with nanomolar potency allowed us to investigate mechanism MGL inhibition. Site-directed mutagenesis mass spectrometry experiments showed BTZs interact in covalent...
The endocannabinoids (
Introduction: Activation of cannabinoid 1 receptors (CB1Rs) by endocannabinoids (eCBs) is controlled both eCB production and inactivation. Accordingly, inhibition hydrolyzing enzymes, monoacylglycerol lipase (MAGL) α/β-hydrolase domain containing 6 (ABHD6), enhances accumulation CB1R activation. It known that MAGL regulates select CB1R-dependent behaviors in mice, including locomotor their modulation psychostimulants, but much less about the effect inhibiting ABHD6 activity on such...
Abstract The most abundant endocannabinoid ( eCB ) in the brain, 2-arachidonoyl glycerol 2-AG) , is hydrolyzed by α/β-hydrolase domain containing 6 ABHD6 ); yet how controls stimuli-dependent increases 2-AG production unknown. To explore this question, we leveraged recently developed sensor, GRAB eCB2.0 and found that stimulation of Neuro2a cells culture with bradykinin BK acting at metabotropic B 2 K receptors ATP ionotropic P2X 7 led to differential levels. triggered levels via...
Abstract Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, anti-tumorigenic effect and clinical benefit are only transient, tumors prone to treatment resistance relapse. To elucidate mechanistic insights into drug resistance, we have established an vitro cellular model of MAPK inhibitor malignant melanoma. The evolved response dosage inhibitor, vemurafenib, PLX4032. We conducted...
Abstract B-cell lymphoma 2 (BCL2) is an important apoptosis regulator during developmental and pathological states, its overexpression a key feature of several malignancies. Genomic data from The Cancer Genome Atlas (TCGA) reveals significant somatic copy number amplification, overexpression, and/or elevated protein activity BCL2 in 50 % diffuse large (DLBC) patients. While canonical role mitochondria-directed well established, the effect on transcriptional metabolic networks remains...
B-cell lymphoma 2 (BCL2) is an important apoptosis regulator during developmental and pathological states, its overexpression a key feature of several malignancies. Genomic data from The Cancer Genome Atlas (TCGA) reveals significant somatic copy number amplification, overexpression, and/or elevated protein activity BCL2 in 50 % diffuse large (DLBC) patients. While canonical role mitochondria-directed well established, the effect on transcriptional metabolic networks remains elusive. Using...