Genomes and Genes
David G McLaren
Affiliation: Merck Research Laboratories
- Evaluation of CETP activity in vivo under non-steady-state conditions: influence of anacetrapib on HDL-TG fluxDavid G McLaren
Merck Research Laboratories, Merck and Co Inc, Kenilworth, NJ 07033
J Lipid Res 57:398-409. 2016....
- Use of [13C18] oleic acid and mass isotopomer distribution analysis to study synthesis of plasma triglycerides in vivo: analytical and experimental considerationsDavid G McLaren
Merck Research Laboratories, Merck and Co, Inc, Kenilworth, New Jersey 07033, USA
Anal Chem 85:6287-94. 2013....
- The use of stable-isotopically labeled oleic acid to interrogate lipid assembly in vivo: assessing pharmacological effects in preclinical speciesDavid G McLaren
Merck Research Laboratories, Merck and Co, Inc Rahway, NJ, USA
J Lipid Res 52:1150-61. 2011....
- Tracking fatty acid kinetics in distinct lipoprotein fractions in vivo: a novel high-throughput approach for studying dyslipidemia in rodent modelsDavid G McLaren
Merck Research Laboratories, Rahway, NJ 07065, USA
J Lipid Res 54:276-81. 2013..We expect that it is possible to translate our approach for application in other systems, including studies in humans...
- Small molecule activation of lecithin cholesterol acyltransferase modulates lipoprotein metabolism in mice and hamstersZhu Chen
Cardiovascular Diseases, Merck Research Laboratories, Rahway, NJ 07065, USA
Metabolism 61:470-81. 2012....
- New methodologies for studying lipid synthesis and turnover: looking backwards to enable moving forwardsStephen F Previs
Molecular Biomarkers, Merck, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA Electronic address
Biochim Biophys Acta 1842:402-13. 2014..This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. ..
- Demonstration of diet-induced decoupling of fatty acid and cholesterol synthesis by combining gene expression array and 2H2O quantificationKristian K Jensen
Department of Atherosclerosis, Merck Research Labs, Merck and Co, Inc, 126 E Lincoln Ave, Rahway, NJ 07065, USA
Am J Physiol Endocrinol Metab 302:E209-17. 2012..In conclusion, by applying gene expression analysis and tracer methodology, we show that fatty acid and cholesterol synthesis are differentially regulated when the carbohydrate intake in mice is altered...
- Anacetrapib promotes reverse cholesterol transport and bulk cholesterol excretion in Syrian golden hamstersJose Castro-Perez
Department of Cardiovascular Diseases, Atherosclerosis, Merck Research Laboratories, Rahway, NJ, USA
J Lipid Res 52:1965-73. 2011....
- Effect of Error Propagation in Stable Isotope Tracer Studies: An Approach for Estimating Impact on Apparent Biochemical FluxStephen F Previs
Merck Research Laboratories, Kenilworth, New Jersey, USA Electronic address
Methods Enzymol 561:331-58. 2015..Likewise, one can facilitate biological studies by estimating the reduction in the noise of an outcome that is expected for a given increase in the number of replicate injections. ..
- Quantitative profiling of oxylipins in plasma and atherosclerotic plaques of hypercholesterolemic rabbitsLazar A Bojic
Merck and Co, Inc, Merck Research Laboratories, Kenilworth, NJ, 07033, USA
Anal Bioanal Chem 408:97-105. 2016..The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis...
- Headspace analyses of ²H labeling of acetone: enabling studies of fatty acid oxidation in vivoAblatt Mahsut
Exploratory Biomarkers Atherosclerosis, Merck Research Laboratories, Rahway, NJ 07065, USA
Anal Biochem 408:351-3. 2011..This method enables routine measurements of fatty acid oxidation in rodents; that is, one administers a ²H-labeled fatty acid(s) and then quantifies the production of ²H-labeled water...
- Localization of fatty acyl and double bond positions in phosphatidylcholines using a dual stage CID fragmentation coupled with ion mobility mass spectrometryJose Castro-Perez
Department of Atherosclerosis Exploratory Biomarkers, Merck Research Laboratories, 126 E Lincoln Ave, 80Y 2D7, Rahway, NJ 07065, USA
J Am Soc Mass Spectrom 22:1552-67. 2011..And was proven to be derived from the α-proximal (carboxylate) or distant ω-position (methyl) in the LPC...
- AAV8-mediated long-term expression of human LCAT significantly improves lipid profiles in hCETP;Ldlr(+/-) miceZhu Chen
Atherosclerosis, Cardiovascular Diseases, Merck Research Laboratories, RY80T A100, 126 E Lincoln Ave, Rahway, NJ 07065, USA
J Cardiovasc Transl Res 4:801-10. 2011..Our findings thus shed new light on LCAT's mechanism of action and lend support to its therapeutic potential in treating dyslipidemia...
- Enhanced data-independent analysis of lipids using ion mobility-TOFMSE to unravel quantitative and qualitative information in human plasmaVinit Shah
Analytical Biochemistry and Molecular Biomarkers, Merck Research Laboratories, Kenilworth, NJ 07033, USA
Rapid Commun Mass Spectrom 27:2195-200. 2013....
- An ultraperformance liquid chromatography method for the normal-phase separation of lipidsDavid G McLaren
Atherosclerosis Research, Merck Research Laboratories, Merck and Co Inc, Rahway, NJ 07065, USA
Anal Biochem 414:266-72. 2011..6 to 10.5% CV with a variability in retention time of less than 6%. The utility of the method is demonstrated through the separation and quantitation of lipids in mouse plasma, liver, and heart tissue...
- An LC-MRM method for measuring intestinal triglyceride assembly using an oral stable isotope-labeled fat challengeXiaofang Li
Merck Research Laboratories, Merck and Co, Inc, Kenilworth, NJ, USA
Bioanalysis 8:1265-77. 2016..Stable isotope-labeled tracers combined with LC-MRM can be used to identify and distinguish TG synthesized with dietary and stored fatty acids...
- Dose-dependent effects of siRNA-mediated inhibition of SCAP on PCSK9, LDLR, and plasma lipids in mouse and rhesus monkeyKristian K Jensen
Cardiometabolic Disease Merck and Co Inc, Kenilworth, NJ
J Lipid Res 57:2150-2162. 2016..In conclusion, siRNA-mediated inhibition of SCAP resulted in a significant reduction in circulating PCSK9 and LDL-C in rodent and primate models supporting SCAP as a novel target for the treatment of dyslipidemia...
- In vivo D2O labeling to quantify static and dynamic changes in cholesterol and cholesterol esters by high resolution LC/MSJose Castro-Perez
Atherosclerosis Exploratory Biomarkers Group, Merck and Co, Inc, Rahway, NJ, USA
J Lipid Res 52:159-69. 2011..We concluded that it is possible to readily obtain static and dynamic measurement of cholesterol and CEs in vivo by coupling novel LC/MS methods with stable isotope-based protocols...
- Lipidome of atherosclerotic plaques from hypercholesterolemic rabbitsLazar A Bojic
Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA
Int J Mol Sci 15:23283-93. 2014..The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome. ..
- Effects of anacetrapib on plasma lipids, apolipoproteins and PCSK9 in healthy, lean rhesus macaquesThomas P Roddy
Merck Research Laboratories, Merck and Co, Inc 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA
Eur J Pharmacol 740:410-6. 2014..Collectively, these data suggest that rhesus macaques may be a useful translational model to study the mechanistic effects of CETP inhibition...
- Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight and modulates gut peptide release--potential insight into mechanism of actionJinqi Liu
Merck Research Laboratories, Rahway, New Jersey, USA
Obesity (Silver Spring) 21:1406-15. 2013..Investigation was conducted to understand the mechanism of action of diacylglycerol acyltransferase 1 (DGAT1) using small molecules DGAT1 inhibitors, compounds K and L...
- Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemiaWu Yin
Department of Atherosclerosis, Merck Research Laboratories, Rahway, NJ 07065, USA
J Lipid Res 53:51-65. 2012..Most traditional models, including rabbit, Zucker diabetic fatty rat, and the majority of mouse models, did not demonstrate overall similarity to dyslipidemic humans in this study...
- Identification of DGAT2 Inhibitors Using Mass SpectrometryXuelei S Song
Department of Pharmacology, Merck Research Laboratories, Boston, MA, USA
J Biomol Screen 21:117-26. 2016..Additional profiling of one chemotype in particular identified two promising reversible and selective compounds (compound 15 and compound 16) that effectively inhibit TG production in mouse primary hepatocytes. ..