A5062929535- Receptor Mechanisms and Signaling
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- RNA and protein synthesis mechanisms
- Cholesterol and Lipid Metabolism
- Gene expression and cancer classification
- Neuropeptides and Animal Physiology
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Metabolomics and Mass Spectrometry Studies
- Chemical Synthesis and Reactions
- Asymmetric Synthesis and Catalysis
- Analytical Chemistry and Chromatography
- Synthesis and Reactions of Organic Compounds
- Eicosanoids and Hypertension Pharmacology
- Synthetic Organic Chemistry Methods
- Genomics and Phylogenetic Studies
- Pharmacogenetics and Drug Metabolism
- Pregnancy-related medical research
- Mast cells and histamine
- Phenothiazines and Benzothiazines Synthesis and Activities
- Sphingolipid Metabolism and Signaling
Janssen (United States)
2012-2022
Springhouse
2020
Analytical Services
2020
Janssen (Belgium)
2014-2017
The Ohio State University
1989-2011
Johnson & Johnson (United States)
2003-2011
Cancer Genetics (United States)
2006-2010
Johnson & Johnson (Israel)
2009
Indiana University Bloomington
2008
Texas A&M University
2006
Lactic acid is a well known metabolic by-product of intense exercise, particularly under anaerobic conditions. Lactate also key source energy and an important substrate, it has been hypothesized to be signaling molecule directing activity. Here we show that GPR81, orphan G-protein-coupled receptor highly expressed in fat, fact sensor for lactate. activates GPR81 its physiological concentration range 1–20 mm suppresses lipolysis mouse, rat, human adipocytes as differentiated 3T3-L1 cells....
The RAR-related orphan receptor gamma t (RORγt) is a nuclear required for generating IL-17-producing CD4(+) Th17 T cells, which are essential in host defense and may play key pathogenic roles autoimmune diseases. Oxysterols elicit profound effects on immune inflammatory responses as well cholesterol lipid metabolism. Here, we describe the identification of several naturally occurring oxysterols RORγt agonists. most potent selective activator 7β, 27-dihydroxycholesterol (7β, 27-OHC). We show...
The increase of insulin resistance in “healthy” aging can be explained by a gut microbiota–monocyte–B1a B cell axis.
Hypermethylation of 5′-cytosine-guanosine islands tumor suppressor genes resulting in their silencing has been proposed to be a hallmark various tumors. Modulation DNA methylation with inhibitors shown result cancer cell differentiation or apoptosis and represents novel strategy for chemotherapy. Currently, effective are mainly limited decitabine 5-azacytidine, which still show unfavorable toxicity profiles the clinical setting. Thus, discovery development hypomethylating agents, more...
Both relaxin-3 and its receptor (GPCR135) are expressed predominantly in brain regions known to play important roles processing sensory signals. Recent studies have shown that is involved the regulation of stress feeding behaviors. The mechanisms underlying involvement relaxin-3/GPCR135 stress, feeding, other potential functions remain be studied. Because also activates relaxin (LGR7), which brain, selective GPCR135 agonists antagonists crucial study physiological vivo. Previously, we...
Niacin raises high-density lipoprotein and lowers low-density through the activation of β-hydroxybutyrate receptor hydroxycarboxylic acid 2 (HCA2) (aka GPR109a) but with an unwanted side effect cutaneous flushing caused by vascular dilation because stimulation HCA2 receptors in Langerhans cells skin. HCA1 GPR81), predominantly expressed adipocytes, was recently identified as a for lactate. Activation adipocytes lactate results inhibition lipolysis, suggesting that agonists may be useful...
GPR139 is an orphan G-protein-coupled receptor expressed in the central nervous system. To identify its physiologic ligand, we measured activity from recombinant cells after treatment with amino acids, ligands, serum, and tissue extracts. was using guanosine 5'-O-(3-[(35)S]thio)-triphosphate binding, calcium mobilization, extracellular signal-regulated kinases phosphorylation assays. Amino acids L-tryptophan (L-Trp) L-phenylalanine (L-Phe) activated GPR139, EC50 values 30- to 300-μM range,...
Receptors from distant species may have conserved functions despite significant differences in protein sequences. Whereas the noncritical residues are often changed species, amino acids critical receptor conserved. Studying between receptors offers valuable information to probe roles of function. We identified two zebrafish (zGPR81-1 and zGPR81-2) that show approximately 60% identity human GPR81, GPR109a, GPR109b but respond only l-lactate not GPR109a ligands. Protein sequence comparison...
Fatty acid amide hydrolase (FAAH) is an integral membrane enzyme within the amidase-signature family. It catalyzes hydrolysis of several endogenous biologically active lipids, including anandamide (arachidonoyl ethanolamide), oleoyl ethanolamide, and palmitoyl ethanolamide. These FAAH substrates have been shown to be involved in a variety physiological pathological processes, synaptic regulation, regulation sleep feeding, locomotor activity, pain inflammation. Here we describe biochemical...
Alternative promoters that are differentially used in various cellular contexts and tissue types add to the transcriptional complexity mammalian genome. Identification of alternative annotation their activity different tissues is one major challenges understanding regulation genes isoforms. To determine use tissues, we performed ChIP-seq experiments using antibody against RNA Pol-II, five adult mouse (brain, liver, lung, spleen kidney). Our analysis identified 38 639 Pol-II promoters,...
Abstract Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over entire genome. ChIP-seq allows scientist get more comprehensive results in shorter time. Here, we present non-linear normalization algorithm and mixture modeling for comparing data from multiple samples characterizing genes based on their RNA polymerase II (Pol II)...
Independent lines of evidence suggested that a large fraction human genes possess multiple promoters driving gene expression from distinct transcription start sites. Understanding which promoter is employed in cellular context required to unravel regulatory networks within the cell.We have developed custom microarray platform tiles roughly 35,000 alternative putative nearly 7,000 genome. To demonstrate utility this array platform, we analyzed patterns usage 17beta-estradiol (E2)-treated and...
Abstract Background Global profiling of in vivo protein-DNA interactions using ChIP-based technologies has evolved rapidly recent years. Although many genome-wide studies have identified thousands ERα binding sites and revealed the associated transcription factor (TF) partners, such as AP1, FOXA1 CEBP, little is known about hierarchical transcriptional regulatory networks. Results In this study, we applied computational approaches to analyze three public available datasets: ChIP-seq,...
Relaxin-3 is a recently discovered member of the insulin/relaxin superfamily that has been shown to be endogenous ligand for G-protein-coupled receptor (GPCR)135 (SALPR). In addition, relaxin-3 demonstrated affinity and functional agonism GPCR142 (GPR100) LGR7 receptors in vitro. Recent evidence suggests insulin-like peptide 5 (INSL5) actual relaxin receptor. We have described chimeric R3/I5 selectively activates GPCR135 GPCR142, but lacks LGR7. pseudogene rat, which allowed use...
Abstract Background Previous studies of individual genes have shown that in a self-enforcing way, dimethylation at histone 3 lysine 9 (dimethyl-H3K9) and DNA methylation cooperate to maintain repressive mode inactive genes. Less clear is whether this cooperation generalized mammalian genomes, such as mouse genome. Here we use epigenomic tools simultaneously interrogate chromatin modifications leukemia cell line, L1210. Results Histone on H3K9 L1210 were profiled by both global CpG island...
Abstract We present a mixture model-based analysis for identifying differences in the distribution of RNA polymerase II (Pol II) transcribed regions, measured using ChIP-seq (chromatin immunoprecipitation following massively parallel sequencing technology). The statistical model assumes that number Pol II-targeted sequences contained within each genomic region follows Poisson distribution. A was then developed to distinguish binding changes an empirical approach and expectation-maximization...
Inhibition of the serine protease enteropeptidase (EP) opens a new avenue to discovery chemotherapeutics for treatment metabolic diseases. Camostat has been used clinically treating chronic pancreatitis in Japan; however, mechanistic basis observed clinical efficacy not fully elucidated. We demonstrate that camostat is potent reversible covalent inhibitor EP, with an inhibition potency (k inact/KI) 1.5 × 104 M-1s-1 High-resolution liquid chromatography-mass spectrometry (LC-MS) showed...