Lau Laboratory

Mike Kimzey

Current Position:

Assay/Product Development Scientist, ProZyme, Hayward, CA

Education

  • Ph.D. Pharmacology and Toxicology, University of Arizona 2006-2010
  • B.S. Pharmacology University of California, Santa Barbara 2000

Achievements:

  • Caldwell Health Sciences Research Fellowship, University of Arizona, Tucson, AZ, 2010
  • NIEHS Human Genes and the Environment (HuGER) Training Program Predoctoral Trainee 2009-2011
  • UA Rsearch Frontiers in Nutritional Sciences Outstanding Student Poster Award 2009
  • Grant: Center for quantized Electronic Structures (QUEST) 1999
  • Scholarship for Excellence in Science: Bank of America 1996

Professional Experience:

  • Quantum Dot 2002-2005
  • Naxcor  2001-2002
  • AmeriCorps 2000-2001
  • National Nanofabrication Users Network Summer 1999
  • University of California, Santa Barbara, Research Assistant 1998-1999

Research Project:

Glyco-oxidation is linked to the pathophysiology of diabetes and diabetic complications. The process of glyco-oxidation generates reactive dicarbonyls, which form adducts on arginine residues in distributions throughout the proteome that are site-specific depending on the protein microenvironment. Dicarbonyl adducts are thus markers for glyco-oxidative stress. Various approaches using mass spectrometry permits the identification, localization, and quantification of these dicarbonyl adducts. Using MG as a model dicarbonyl, a shotgun proteomics approach identified the sites for modification of major plasma proteins. Thirty five sites on seven abundant plasma proteins were found, and investigation into the microenvironment surrounding the target arginine sites revealed a neighboring charged residue motif where adjacent residues were either negatively or positively charged. One of the sites identified was R257 in HSA, which is located in the important drug binding site I. We validated drug site I as a target for MG modification by the adaptation of two assays to monitor the effect of MG modification. MG significantly decreases the rate of hydrolysis of PGE2 in drug site I, and induces the displacement of prodan from drug site I. Molecular modeling of warfarin docking at drug site I with the MG-modified R257 resulted in significantly decreased binding and change in binding orientation. The oxidation products of susceptible residues methionine, tryptophan, and cysteine were also evaluated using multiple reaction monitoring (MRM) approach of oxidized HSA peptides. Dicarbonyl modification was independent of arginine solvent accessibility. In a clinical study using nephropathy as an endpoint, sites of oxidation and dicarbonyl modification of HSA were quantified by MRM. The most important variable among diabetic subjects was metformin use, and subjects taking metformin had significantly reduced markers for glyco-oxidation. These findings may be useful in the development of new diabetes therapies that aim to ameliorate glyco-oxidative stress.

Publications:

  • Kimzey, M.J., Zarate, X., Galbraith, D.W. and Lau, S.S. Optimizing microarray-based in situ transcription-translation of proteins for MALDI mass spectrometry, Anal. Biochem. 414: 282-286, 2011.
  • Kimzey, M.J., Yassine, H.N., Riepel, B.M., Tsaprailis, G., Monks, T.J. and Lau, S.S. New Site(s) of Methylglyoxal-modified human serum albumin, identified by multiple reaction monitoring, alter warfarin binding and prostaglandin metabolism. Chemico-Biol Int. 192: 122-128, 2011.

Abstracts:

  • Identification of Hydroimidazolone And Argpyrimidine Adducts as Glycooxidative Biomarkers in Type 2 Diabetic Subjects. Kinsky, O.R., Kimzey, M.J., Yassine, H.N., Stump, C.S., Tsaprailis, G., Monks, T.J. and Lau, S.S. Toxicologist, 105, 913, 2011.

  • Quantitation of Proteomic Markers of Glyco-Oxidation Using Multiple Reaction Monitoring. Kimzey, M.J., Yassine, H.N., Stump, C.S., Tsaprailis, G., Monks, T.J. and Lau, S.S. VIII International Symposium on Biological Reactive Intermediates Abstract Proceeding, Barcelona, Spain July 15-18, 2010.

  • Quantitative Analysis of Oxidative Modifications in HDL using MRM. Yassine, H.N., Kimzey, M.J., Galligan, M.A., Stump, C.S., Tsaprailis, G. and Lau, S.S. J. Am. Soc. Mass. Spec., ThP06, 141, 2010.

  • Effect of Glyco-oxidative Modifications on Plasma Fibrinogen Function in Diabetes. Yassine, H.N., Kimzey, M.J., Galligan, M.A., Stump, C.S., Tsaprailis, G. and Lau, S.S. J. Am. Soc. Mass. Spec., ThP06, 162, 2010.

  • Quantitation of Proteomic Markers of Glyco-Oxidation Using Multiple Reaction Monitoring. Kimzey, M.J., Yassine, H.N., Galligan, M., Stump, C.S., Tsaprailis, G. and Lau, S.S. J. Am. Soc. Mass. Spec., TP07, 188, 2010.

  • MALDI-MS-based drug and protein imaging to simultaneously determine drug disposition and protein modification in cells. Mastrandrea, N.J. Cohen, J.D., Kimzey, M., Monks, T.J. and Lau, S.S. Toxicologist, 104, 1667, 2010.

  • Identification of candidate plasma biomarkers for diabetic complications: In vivo methylglyoxal modified hotspots. Kimzey, M., Galligan, M.A., Yassine, H., Stump, C., Tsaprailis, G. and Lau, S.S. J. Am. Soc. Mass. Spec., ThPV565, 20(5S), S143, 2009.

  • Plasma methylglyoxal and correlation with the severity of diabetic albuminuria. Yassine, H., Kimzey, M., Alvarez, I., Stratton, S. Stump, S., Tsaprailis, G., Galligan, M.A. and Lau, S.S. J. Am. Soc. Mass. Spec., TPZ624, 20(5S), S84, 2009.

  • Identification of candidate plasma biomarkers for type-2 diabetes: in vivo methylglyoxal modified hotspots. Kimzey, M., Galligan, M.A., Yassine, H., Stump, C.,  Tsaprailis, G. and Lau, S.S. Late Breaking Abstracts, 2009 Annual Meeting of the Society of Toxicology, Baltimore, MD.

  • Biofluid proteomic analysis in high fat-fed, insulin-resistant rats before the onset of diabetes. Stump, C.S., Tsaprailis, G, Henriksen, E.J., Galligan, M., Kimzey, M., Teachey, M.K., Link, C. D., Lau, S.S. Abstract # 2590-PO, Am. Diabetes Association, June 6-8, 2008.

  • Proteomic analysis of rat and human plasma in search of potential biomarkers for Type 2 Diabetes. Galligan, M., Kimzey, M., Radabaugh, T.R., Tsaprailis, G., Link, D.C., Borges, C.R., Yassine, H., Henriksen, E.J., Nelson, R., Stump, C.S., and Lau, S.S. J. Am. Soc. Mass. Spec., Poster number MP526, 19(5S), S50, 2008.

  • Identification of methyglyoxal modified proteins in diabetic plasma using MudPIT. Kimzey, M., Galligan, M., Radabaugh, T.R., Borges, C.R., Yassine, H., Nelson, R., Link, D.C., Henriksen, E.J., Stump, C.S., Tsaprailis, G., Lau, S.S. J. Am. Soc. Mass. Spec., Poster number TP463, 19(5S), S76, 2008.

  • MALDI-based mass spectrometric characterization of protein microarrays and tissue sections. Galbraith, D. W., Leinweber, B., Kimzey, M., Zarate, X. and Lau, S. S. Keystone Symposium: HIV Vaccines From Basic Research to Clinical Trials, Poster number 127, 2007.

  • Detecting Self-Assembled Protein Microarrays by MALDI-TOF. Kimzey, K., Zarate, X., Galbraith, D. W., and Lau, S. S. J. Am. Soc. Mass. Spec., Poster number TPZ2-474, p.55, 2007.

Past and present staff

Present Graduate Students

Ryan Canatsey | Owen Kinsky | Chris Kuhlman | Nick Mastrandrea | Jessica Sapiro | Kevin Xu


Present Postdoctoral Fellow
Tim Radabaugh

Research Associate

Alfred Gallegos

Clinical Faculty Mentee

Hussein Yassine

Current Undergraduate Students

Wesley Cai, Itzel Rojas, Audrey Shi, Kim Tham


Recent Past Staff
Martina Bowen | Jennifer Cohen | Ashley Fisher | Chris Hattan | Mike Kimzey | Matt Labenski | Jean Lord-Garcia

 

 

 

 

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