A5071664411- Protein Kinase Regulation and GTPase Signaling
- Sphingolipid Metabolism and Signaling
- Receptor Mechanisms and Signaling
- Histone Deacetylase Inhibitors Research
- Inflammatory mediators and NSAID effects
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Lipid Membrane Structure and Behavior
- Ion Channels and Receptors
- Metabolism, Diabetes, and Cancer
- Cancer-related gene regulation
- Pain Mechanisms and Treatments
- Lysosomal Storage Disorders Research
- Phosphodiesterase function and regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Phytochemicals and Antioxidant Activities
- Cancer, Lipids, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Adenosine and Purinergic Signaling
- Neurological Disorders and Treatments
University of Georgia
2013-2023
Georgia College & State University
2018
Piedmont Athens Regional
2017
Georgia State University
2016
University of North Carolina at Chapel Hill
2003-2004
University of Virginia
1998-2001
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links open access knowledgebase source and their ligands (www.guidetopharmacology.org), which more detailed views target ligand properties. Although constitutes over 500 pages, material presented substantially reduced compared...
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties approximately 1800 drug targets, and about 6000 interactions with 3900 ligands. There an emphasis on selective pharmacology (where available), plus links open access knowledgebase source targets their ligands ( www.guidetopharmacology.org ), which more detailed views target ligand properties. Although constitutes almost 500 pages,...
RGS10 is an important regulator of cell survival and chemoresistance in ovarian cancer. We recently showed that transcript expression suppressed during acquired The suppression due to DNA hypermethylation histone deacetylation, two mechanisms contribute silencing tumor suppressor genes cancer progression. Here, we fully investigate the molecular epigenetic chemoresistant A2780-AD cells. identify regulators, HDAC1 DNMT1, exhibit aberrant association with promoters Knockdown or DNMT1...
Regulator of G-protein signaling (RGS) proteins are GTPase activating (GAPs) heterotrimeric G-proteins that alter the amplitude and kinetics receptor-promoted signaling. In this study we defined alpha-subunit selectivity purified Sf9 cell-derived R7 proteins, a subfamily RGS (RGS6, -7, -9, -11) containing Ggamma-like (GGL) domain mediates dimeric interaction with Gbeta(5). Gbeta(5)/R7 dimers stimulated steady state activity Galpha-subunits G(i) family, but not Galpha(q) or Galpha(11), when...
Lysophosphatidic acid (LPA) is an extracellular signaling mediator with a broad range of cellular responses. Three G-protein-coupled receptors (Edg-2, -4, and -7) have been identified as for LPA. In this study, the ectophosphatase lipid phosphate phosphatase 1 (LPP1) has shown to down-regulate LPA-mediated mitogenesis. Furthermore, using degradation-resistant phosphonate analogs LPA stereoselective agonists Edg we demonstrated that mitogenic platelet aggregation responses are independent...
A critical therapeutic challenge in epithelial ovarian carcinoma is the development of chemoresistance among tumor cells following exposure to first line chemotherapeutics. The molecular and genetic changes that drive are unknown, this lack mechanistic insight a major obstacle preventing predicting occurrence refractory disease. We have recently shown Regulators G-protein Signaling (RGS) proteins negatively regulate signaling by lysophosphatidic acid (LPA), growth factor elevated malignant...
Regulator of G-protein signalling (RGS)(2) proteins critically regulate cascades initiated by coupled receptors (GPCRs) accelerating the deactivation heterotrimeric G-proteins. Lysophosphatidic acid (LPA) is predominant growth factor that drives progression ovarian cancer activating specific GPCRs and G-proteins expressed in cells. We have recently reported RGS endogenously SKOV-3 cells dramatically attenuate LPA stimulated cell signalling. The goal this study was twofold: first, to identify...
Abstract Patients receiving paclitaxel for cancer treatment often develop an acute pain syndrome (paclitaxel‐associated syndrome, P‐APS), which occurs immediately after treatment. Mechanisms underlying P‐APS remain largely unknown. We recently reported that rodents and activation of spinal microglial toll like receptor 4 (TLR4) by penetrating into the cord is a critical event in genesis P‐APS. Our current study dissected cellular molecular mechanisms demonstrated bath‐perfusion paclitaxel,...
Two human isoforms of membrane associated phosphatidic acid phosphatase have been described (PAP‐2a and ‐2b), both enzymes shown to broad substrate specificity wide tissue distribution [Kai et al., J. Biol. Chem. 272 (1997) 24572–24578]. With this report we describe a third isoform, PAP‐2c, that found by searching the database expressed sequence tags (dbEST) with PAP‐2a PAP‐2b sequences. Key structural features previously in ‐2b, including glycosylation site, putative transmembrane domains,...
The human P2Y12 receptor (P2Y12-R) is a member of the G protein coupled P2Y family, which intimately involved in platelet physiology. We describe here purification and functional characterization recombinant P2Y12-R after high-level expression from baculovirus Sf9 insect cells. Purified P2Y12-R, Gbeta1gamma2, various Galpha-subunits were reconstituted lipid vesicles, steady-state GTPase activity was quantified. GTP hydrolysis proteoliposomes formed with purified Galphai2beta1gamma2...
RGS10 regulates ovarian cancer cell growth and survival, expression is suppressed in models of chemoresistance. However, the mechanisms governing are poorly understood. Here we report suppression primary CAOV-3 cells compared to immortalized surface epithelial (IOSE) cells, A2780-AD chemoresistant parental A2780 cells. RGS10-1 RGS10-2 transcripts expressed but only promoter uniquely enriched CpG dinucleotides. Pharmacological inhibition DNA methyl-transferases (DNMTs) increased expression,...
RGS10 has emerged as a key regulator of proinflammatory cytokine production in microglia, functioning an important neuroprotective factor. Although is normally expressed microglia at high levels, expression silenced vitro following activation TLR4 receptor. Given the ability to regulate inflammatory signaling, dynamic regulation levels may be mechanism tune responses. The goals current study were confirm that suppressed vivo model microglial and determine for activation-dependent silencing...
Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, progenitors. A stable human progenitor line is not currently available in which to study role lysophospholipids development. We recently established a stable, adherent embryonic stem cell-derived neuroepithelial (hES-NEP) recapitulates morphological phenotypic features cells isolated from fetal tissue. The goal this was determine if hES-NEP express functional lysophospholipid receptors,...
The small regulator of G protein signaling RGS10 is a key neuroinflammation and ovarian cancer cell survival; however, the mechanism for function in these cells unknown has not been linked to specific pathways. highly enriched microglia, loss expression microglia amplifies production inflammatory cytokine tumor necrosis factor <i>α</i> (TNF<i>α</i>) enhances microglia-induced neurotoxicity. also regulates survival chemoresistance cells. Cyclooxygenase-2 (COX-2)–mediated prostaglandins such...
Despite an intriguing cell biology and the suggestion of a role in pathophysiological responses, mechanism action such lipid phosphoric acid mediators as lysophosphatidic (LPA) remains obscure, part because underdeveloped medicinal chemistry. We report now agonist activity synthetic phospholipid which glycerol backbone LPA is replaced by l-serine. Like LPA, l-serine-based mobilizes calcium inhibits activation adenylyl cyclase human breast cancer line MDA MB231. Treatment with desensitizes...