个人简介

South Dakota State University - B.S. (1980) Purdue University - M.S. (1982) University of California, Riverside - Ph.D. (1992) University of Illinois - Visiting Scholar (2001) Awards Chair, ACS Division of Analytical Chemistry, 2013 ACS Fellow, 2011 UC-Riverside Innovative Teaching Award, 2011 Program Chair, ACS Division of Analytical Chemistry 2012 Chair-elect, ACS Division of Analytical Chemistry 2011 AAAS Fellow, 2008 J. Calvin Giddings Award for Excellence in Education, ACS Division of Analytical Chemistry, 2007 Honorary Doctorate, College of Pharmacy, Semmelweis University, Budapest, Hungary, 2005 IUPAC Fellow, 2004 Award for Teaching Excellence, 2002 (selected by Chemistry undergraduate students) IUPAC Young Observer, 2001 Kaw Valley Girl Scout Woman of Distinction, 1997 Eli Lilly New Faculty Award, 1996 National Science Foundation CAREER Award, 1995 Orange County Graduate Women in Science Scholarship, 1991 U.C. Riverside Dissertation Fellowship, 1991 National ACS Division of Analytical Chemistry Full-year Fellow, 1990 U.C. Riverside Chancellor's Distinguished Fellow 1988, 1989 S.D.S.U. Stephen Briggs Scholarship, 1976-1980 S.D.S.U. Outstanding Analytical Chemistry Student, 1979

研究领域

Analytical Chemistry/Chemical Biology

Our research group works mainly in the area of bioanalytical chemistry. We take a problem solving approach to analytical chemistry that involves identifying interesting problems, and applying various analytical tools to address the question at hand. Therefore, we employ a variety of analytical techniques in our research including separations (CE, HPLC, UPLC. GC) and characterization tools, especially NMR and mass spectrometry. Sometimes we find that the technology needs to be improved to allow us to fully address a question of interest. Development and Application of Microcoil NMR Probes One area where we are involved in technology development is in the use of microcoil NMR probes to improve the sensitivity of NMR measurements. Microcoil NMR probes constructed in our laboratory, capable of measuring volumes of 25 nL, permit on-line NMR detection with capillary isotachophoresis (cITP). An example of an NMR microcoil is shown in this photo. The coil, approximately 1 mm in length, is made by winding copper wire around a polyimide sleeve. Our group is using the on-line concentration and separation method of cITP coupled with NMR detection to study a number of problems related to structure elucidation including analysis of trace pharmaceutical impurities and characterization of heparin and heparan oligosaccharides. Characterization and Biochemistry of Heparin and Heparan Sulfate Analysis strategies are being developed in our laboratory to greatly reduce the quantity of heparin or heparan sulfate required for structure elucidation. Oligosaccharides are obtained by enzymatic depolymerization and are size-separated by gel permeation chromatography. The size-fractionated materials are profiled using capillary electrophoresis and fractionated further with ion-pairing UPLC. With cITP-NMR using our microcoil NMR probes, a proton NMR spectrum can be obtained during the on-line separation with as little as 1 - 2 micrograms of sample. Complete 2D NMR spectra can be recorded in static mode with 20 - 30 micrograms. Since NMR is non-destructive, samples can be collected for subsequent MS/MS characterization using our Q-TOF mass spectrometer. Metabonomics Studies for Chemical Genomics in Arabidopsis thaliana The goal of metabonomics studies is to collect as much chemical information as possible about the identity and relative concentrations of endogenous metabolites in samples from control and treated (perturbed) organisms. The choice of perturbation is at the discretion of the experimenter and can be designed to probe the effects of a drug, toxicant or genetic modification. In our case, we are probing the effect of chemicals (for example herbicides) applied to plants. In collaboration with Julia Bailey-Serres we are also studying the response of plants to hypoxia. Analytical methods such as 1H NMR, LC-MS and GC-MS are used in metabonomics studies because they produce data sets with high information content. Data reduction by principal components analysis (PCA) or other statistical methods is used to group samples based on their chemical similarity and to identify the compounds responsible for differences between the control and treated groups. Understanding Ligand-Protein Interactions Specific ligand-protein interactions are integral to the ability of proteins to carry out processes vital for human life such as enzymatic transformations, receptor and antibody recognition, and signal transduction. Therefore the study of ligand-protein interactions is important for understanding the biochemical basis of many diseases and provides an opportunity for the development of pharmaceutical compounds with agonistic or inhibitory activity. NMR is a useful analytical tool for the study of ligand-protein binding, because changes can be detected when a small ligand interacts with a macromolecular target without the need for special labels. We have developed experiments that provide improved spectral selectivity in ligand binding studies by manipulation of NMR pulse sequences to reduce the protein background or enhance specificity in cases where several ligands are studied simultaneously. In addition to providing information about the strength of the interaction, the build-up of transferred-NOEs during the diffusion experiment can provide insight into the nature of ligand-protein binding and can be used to prepare an epitope map of the ligand which is useful for the elucidation of structure activity relationships.

近期论文

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D. J. Langeslay, E. Urso, C. Gardini, A. Naggi, G. Torri, C. K. Larive "Reverse-phase Ion-pair UPLC-MS for Fingerprinting Low-Molecular-Weight Heparins" J. Chromatogr. A.1292:201-210 (2013). D. J. Langeslay, C.N. Beecher, A. Naggi, M. Guerrini, G. Torri, C. K. Larive "Characterizing the Microstructure of Heparin and Heparan Sulfate using 1H and 15N NMR Chemical Shift Analysis" Anal. Chem. 85:1247-1255 (2013). G. A. Barding, Jr., T. Fukao, S. Beni, J. Bailey-Serres, C. K. Larive "Comparison of GC-MS and NMR for Metabolite Profiling of Rice Subjected to Submergence Stress" J. Proteome Res. 12:898-909 (2013). C. J. Jones, C. K. Larive "Microcoil NMR Study of the Interactions between Doxepin, β-Cyclodextrin, and Acetate during Capillary Isotachophoresis" Anal. Chem. 84:7099-7106 (2012). G. A. Barding, Jr., R. Salditos, C. K. Larive "Quantitative NMR for Bioanalysis and Metabolomics" Anal. Bioanal. Chem. 404:1165-1179 (2012). D. J. Langeslay, R. P. Young, S. Beni, C. N. Beecher, L. J. Mueller, C. K. Larive "Sulfamate Proton Solvent Exchange in Heparin Oligosaccharides - Evidence for a Persistent Hydrogen Bond in the Antithrombin-binding Pentasaccharide Arixtra" Glycobiology 9:1173-1182 (2012). D.N. Bulloch, R. Lavado, K. L. Forsgren, S. Beni, D. Schlenk, C.K. Larive "Analytical and Biological Characterization of Halogenated Gemfibrozil Produced through Chlorination of Wastewater" Environ. Sci. Tech. 46:5583-5589 (2012). D. J. Langeslay, S. Beni, C.K. Larive "A Closer Look at the Nitrogen Next Door: 1H-15N NMR Methods for Glycosaminoglycan Structural Characterization" J. Magn. Reson. 216:169-174 (2012). J.F.K. Limtiaco, C.J. Jones, C. K. Larive "Diffusion-edited NMR spectra of heparin contaminants" Anal. Methods, 4:1168-1172 (2012). G. A. Barding, Jr., T. Fukao, Sz. Beni, J. Bailey-Serres, C. K. Larive "Differential Metabolic Regulation Governed by the Rice SUB1A Gene during Submergence Stress and Identification of Alanylglycine by 1H NMR Spectroscopy" J. Proteome Res. 11:320-330 (2012). J. R. Cruz, C. K. Larive "Determination of the Binding Epitope of Lidocaine with AGP: Minimizing the Effects of Nonspecific Binding in Saturation Transfer Difference Experiments" Anal. Bioanal. Chem. 402:337-347 (2012). C.J. Jones, C. K. Larive, "Could Smaller Really be Better? Current and Future Trends in Microcoil NMR" Anal. Bioanal. Chem. 402:61-68 (2012). D. J. Langeslay, Sz. Beni, C. K. Larive "Detection of the 1H and 15N NMR Resonances of Sulfamate Groups in Aqueous Solution - a New Tool for Heparin and Heparan Sulfate Characterization" Anal.Chem. 83:8006-8010 (2011). A.M. Johnson, O. Moshe, A.S. Gamboa, B. W. Langloss, J.F. K. Limtiaco, C.K. Larive, R.J. Hooley "Synthesis and Properties of Metal-Ligand Complexes with Endohedral Amine Functionality" Inorg. Chem. 50:9430-9442 (2011). C.J. Jones, Sz. Beni, C. K. Larive "Understanding the Reverse-phase Ion-pair HPLC Resolution of Heparin-Related Saccharide Anomers" Anal. Chem. 83:6762-6769 (2011). J.F.K. Limtiaco, Sz. Beni, C.J. Jones, D. J. Langeslay, C.K. Larive "The Efficient Structure Elucidation of Minor Components in Heparin Digests using Microcoil NMR" Carbohydrate Res. 346: 2244-2254 (2011). J. D. Kim, K. Kaiser, C. K. Larive, K.A. Borkovich, "Use of 1H NMR to Measure Intracellular Metabolite Levels During Growth and Asexual Sporulation in Neurospora crassa" Eukaryotic Cell 10:820-831 (2011). J.F.K. Limtiaco, D. J. Langeslay, S. Beni, C.K. Larive "Getting to Know the Nitrogen Next Door: HNMBC Measurements of Amino Sugars" J. Magn. Reson. 209:323-331 (2011). J.F.K. Limtiaco, Sz. Beni, C.J. Jones, D. J. Langeslay, C. K. Larive "NMR Methods to Monitor the Enzymatic Depolymerization of Heparin" Anal. Bioanal. Chem. 399:593-603 (2011). (Paper in Forefront). Sz. Beni, J.F. K. Limtiaco, C. K. Larive "Analysis and Characterization of Heparin Impurities" Anal. Bioanal. Chem. 399:527-539 (2011).