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Richard Zangar

Systems Toxicology & Exposure Science
Scientist
Pacific Northwest National Laboratory
PO Box 999
MSIN: J4-02
Richland, WA 99352
509/371-7301

Biography

Dr. Richard Zangar is a level V scientist in Systems Toxicology group that is in the Fundamental and Computational Sciences Directorate at the Pacific Northwest National Laboratory. He is principal investigator on two projects from the National Institutes of Health and a co-investigator on two other projects. He has authored over 80 publications.

Dr. Zangar's research group has developed a sophisticated sandwich ELISA microarray platform, including a suite of supporting bioinformatics software. This platform has been rigorously tested and optimized, and has been shown to be suited for analysis of human and rodent samples from clinical, preclinical and cell-culture studies. A recent study examined nitration of 24 individual proteins in 458 human plasma samples, with each analysis performed in triplicate, for a total of over 30,000 individual sandwich ELISAs. The results demonstrated changes in protein nitration that was associated with smoking and chronic obstructive pulmonary disease (COPD).

Research Interests

  • Circulating protein biomarkers for human diseases with an emphasis on breast cancer, pulmonary disease, and oxidative protein modifications.

Education and Credentials

  • Ph.D., Toxicology, Oregon State University, 1992
  • M.S., Biology, Washington State University, 1986
  • B.S., Environmental Science, Western Washington University, 1982

Affiliations and Professional Service

  • American Association for the Advancement of Science
  • American Cancer Society
  • Society of Toxicology

PNNL Publications

2013

  • Huang CS, V Chaudhey, A Pokhriyal, S George, J Polans, M Lu, R Tan, RC Zangar, and BT Cunningham. 2013. "Multiplexed Cancer Biomarker Detection Using Quartz-based Photonic Crystal Surfaces." Analytical Chemistry 84(2):1126-1133.  doi:10.1021/ac202817q
  • Tilton SC, KM Waters, NJ Karin, BJM Webb-Robertson, RC Zangar, MK Lee, DJ Bigelow, JG Pounds, and RA Corley. 2013. "Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin." Toxicology and Applied Pharmacology 262(2):137-148.  doi:10.1016/j.taap.2012.12.020

2012

  • Jin H, and RC Zangar. 2012. "High-Throughput, Multiplexed Analysis of 3-Nitrotyrosine in Individual Proteins." Current Protocols in Toxicology 51:17.15.1-17.15.16.  doi:10.1002/0471140856.tx1715s51
  • Chaudhey V, M Lu, CS Huang, J Polans, R Tan, RC Zangar, and BT Cunningham. 2012. "Line-scanning detection instrument for photonic crystal enhanced fluorescence." Optics Letters 37(13):2565-2567.  doi:10.1364/OL.37.002565
  • Cunningham BT, and RC Zangar. 2012. "Photonic Crystal Enhanced Fluorescence for Early Breast Cancer Biomarker Detection." Journal of Biophotonics 5(8-9):617-628. 

2011

  • Baird CL, R Tan, CJ Fischer, KD Victry, RC Zangar, and KD Rodland. 2011. "Reducing heterophilic antibody interference in immunoassays using single chain antibodies." Analytical Biochemistry 419(2):333-335.  doi:10.1016/j.ab.2011.08.025
  • Orr G, WB Chrisler, KJ Cassens, R Tan, BJ Tarasevich, LM Markillie, RC Zangar, and BD Thrall. 2011. "Cellular Recognition and Trafficking of Amorphous Silica Nanoparticles by Macrophage Scavenger Receptor A." Nanotoxicology 5(3):296-311.  doi:10.3109/17435390.2010.513836
  • White AM, DS Daly, and RC Zangar. 2011. "Analysis of High-Throughput ELISA Microarray Data." In Bioinformatics for Comparative Proteomics, Methods in Molecular Biology, vol. 694, ed. CH Wu and C Chen, pp. 191-211.  Humana Press, New York, NY. 
  • Gonzales RM, Q Zhang, RC Zangar, RD Smith, and TO Metz. 2011. "Development of a Fibrinogen-Specific Sandwich Enzyme-Linked Immunosorbent Assay Microarray Assay for Distinguishing Between Blood Plasma and Serum Samples." Analytical Biochemistry 414(1):99-102.  doi:10.1016/j.ab.2011.02.039
  • Gonzales RM, DS Daly, R Tan, JR Marks, and RC Zangar. 2011. "Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES is Consistently Increased." Cancer Epidemiology, Biomarkers and Prevention 20(7):1543-1551.  doi:10.1158/1055-9965.EPI-10-1248
  • Huang CS, S George, M Lu, V Chaudhey, R Tan, RC Zangar, and BT Cunningham. 2011. "Application of photonic crystal enhanced fluorescence to cancer biomarker microarrays." Analytical Chemistry 83(4):1425-1430.  doi:10.1021/ac102989n
  • Jin H, BJM Webb-Robertson, ES Peterson, R Tan, DJ Bigelow, MB Scholand, JR Hoidal, JG Pounds, and RC Zangar. 2011. "Smoking, COPD and 3-Nitrotyrosine Levels of Plasma Proteins." Environmental Health Perspectives 119(9):1314-1320.  doi:10.1289/ehp.1103745
  • Teeguarden JG, BJM Webb-Robertson, KM Waters, A Murray, E Kisin, SM Varnum, JM Jacobs, JG Pounds, RC Zangar, and A Shvedova. 2011. "Comparative Proteomics and Pulmonary Toxicity of Instilled Single Walled Carbon Nanotubes, Crocidolite Asbestos and Ultrafine Carbon Black in Mice." Toxicological Sciences 120(1):123-135.  doi:10.1093/toxsci/kfq363
  • Varnum SM, BJM Webb-Robertson, N Hessol, RD Smith, and RC Zangar. 2011. "Plasma Biomarkers for Detecting Hodgkin's Lymphoma in HIV Patients." PLoS One 6(12):Article No. e29263.  doi:10.1371/journal.pone.0029263
  • Zangar RC, N Bollinger, TJ Weber, R Tan, LM Markillie, and NJ Karin. 2011. "Reactive Oxygen Species Alter Autocrine and Paracrine Signaling." Free Radical Biology & Medicine 51(11):2041-2047.  doi:10.1016/j.freeradbiomed.2011.09.001
  • Zhang Y, RM Gonzalez-Hernandez, and RC Zangar. 2011. "Protein Secretion in Human Mammary Epithelial Cells following HER1 Receptor Activation: Influence of HER2 and HER3 Expression." BMC Cancer 11:Article No. 69.  doi:10.1186/1471-2407-11-69

2010

  • Jin H, and RC Zangar. 2010. "Antibody Microarrays for High-Throughput, Multianalyte Analysis." Cancer Biomarkers 6(5-6):281-290.  doi:10.3233/CBM-2009-0140
  • Daly DS, KK Anderson, SL Seurynck-Servoss, RM Gonzalez, AM White, and RC Zangar. 2010. "An internal calibration method for protein-array studies ." Statistical Applications in Genetics and Molecular Biology 9(1):Article Number: 14. 

2009

  • Gonzalez RM, SM Varnum, and RC Zangar. 2009. "Sandwich ELISA Microarrays: Generating Reliable and Reproducible Assays for High-Throughput Screens ." Chapter 13 in Biomarker Methods in Drug Discovery and Development, ed. F Weng, pp. 273-290.  Humana Press, Totowa, NJ. 
  • Jin H, and RC Zangar. 2009. "Protein Modifications as Potential Biomarkers in Breast Cancer ." Biomarker Insights 2009(4):191-200. 
  • White AM, JL Collett, SL Seurynck-Servoss, DS Daly, and RC Zangar. 2009. "ELISA-BASE: An Integrated Bioinformatics Tool for Analyzing and Tracking ELISA Microarray Data." Bioinformatics 25(12):1566-1567. 
  • Servoss S, RM Gonzalez, SM Varnum, and RC Zangar. 2009. "High-Throughput Analysis of Serum Antigens Using Sandwich ELISAs on Microarrays." Chapter 10 in Tumor Biomarker Discovery, Methods in Molecular Biology, vol. 520, pp. 143-150.  Humana Press, Totowa, NJ. 
  • Springer DL, JH Miller, SL Spinelli, L Pasa-Tolic, SO Purvine, DS Daly, RC Zangar, S Jin, N Blumberg, CW Francis, MB Taubman, AE Casey, SD Wittlin, and RP Phipps. 2009. "Platelet Proteome Changes Associated with Diabetes and During Platelet Storage for Transfusion." Journal of Proteome Research 8(5):2261-2272. 
  • Waters KM, LM Masiello, RC Zangar, BJ Tarasevich, NJ Karin, RD Quesenberry, S Bandyopadhyay, JG Teeguarden, JG Pounds, and BD Thrall. 2009. "Macrophage Responses to Silica Nanoparticles are Highly Conserved Across Particle Sizes." Toxicological Sciences 107(2):553-569. 
  • Zangar RC, DS Daly, A White, S Servoss, R Tan, and JR Collett. 2009. "ProMAT Calibrator: A Tool for Reducing Experimental Bias in Antibody Microarrays." Journal of Proteome Research 8(8):3937-3943. 

2008

  • Gonzalez RM, S Servoss, SA Crowley, M Brown, G Omenn, D Hayes, and RC Zangar. 2008. "Development and Validation of Sandwich ELISA Microarrays with Minimal Assay Interference." Journal of Proteome Research 7(6):2406-2414. 
  • Daly DS, KK Anderson, AM White, RM Gonzalez, SM Varnum, and RC Zangar. 2008. "Predicting protein concentrations with ELISA microarray assays, monotonic splines and Monte Carlo simulation." Statistical Applications in Genetics and Molecular Biology 7(1):Article 21. 
  • Rodland KD, N Bollinger, DL Ippolito, L Opresko, RJ Coffey, RC Zangar, and HS Wiley. 2008. "Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells." Journal of Biological Chemistry 283(46):31477-31487.  doi:10.1074/jbc.M800456200
  • Seurynck-Servoss SL, CL Baird, KD Miller, NB Pefaur, RM Gonzalez, DO Apiyo, HE Engelmann, S Srinivastava, J Kagan, KD Rodland, and RC Zangar. 2008. "Immobilization strategies for single-chain antibody microarrays." Proteomics 8(11):2199-2210.  doi:10.1002/pmic.200701036
  • Zangar RC, N Bollinger, S Verma, NJ Karin, and Y Lu. 2008. "The Nuclear Factor-kB Pathway Regulates Cytochrome P450 3A4 Protein Stability." Molecular Pharmacology 73(6):1652-1658. 

2007

  • Seurynck-Servoss SL, CL Baird, KD Rodland, and RC Zangar. 2007. "Surface chemistries for antibody microarrays." Frontiers in Bioscience 12:3956-3964.  doi:10.2741/2362
  • Seurynck-Servoss SL, AM White, CL Baird, KD Rodland, and RC Zangar. 2007. "Evaluation of Surface Chemistries for Antibody Microarrays." Analytical Biochemistry 371(1):105-115. 

2006

  • White AM, DS Daly, SM Varnum, KK Anderson, N Bollinger, and RC Zangar. 2006. "ProMAT: protein microarray analysis tool ." Bioinformatics 22(10):1278-1279.  doi:10.1093/bioinformatics/btl093
  • Zangar RC. 2006. "An ELISA Microarray Platform for Validating Cancer Biomarkers." BIOforum Europe 10:14-15. 
  • Zangar RC, DS Daly, and AM White. 2006. "ELISA microarray technology as a high-throughput system for cancer biomarker validation ." Expert Review of Proteomics 3(1):37-44.  doi:10.1586/14789450.3.1.37

2005

  • Zangar RC. 2005. "Alterations in hepatic cholesterol levels in response to drugs that induce cytochrome P450 3A23." International Journal of Pharmacology 1(2):172-179. 
  • Adkins JN, ME Monroe, KJ Auberry, Y Shen, JM Jacobs, DG Camp, II, F Vitzthum, KD Rodland, RC Zangar, RD Smith, and JG Pounds. 2005. "A Proteomic Study of the HUPO Plasma Proteome Project's Pilot Samples using an Accurate Mass and Time Tag Strategy." Proteomics 5(13):3454-3466.  doi:10.1002/pmic.200401333
  • Daly DS, AM White, SM Varnum, KK Anderson, and RC Zangar. 2005. "Evaluating concentration estimation errors in ELISA microarray experiments." BMC Bioinformatics 6:17.  doi:10.1186/1471-2105-6-17.
  • Zangar RC, SM Varnum, and N Bollinger. 2005. "Studying cellular processes and detecting disease with protein microarrays." Drug Metabolism Reviews 37(3):473-87. 

2004

  • Varnum SM, RL Woodbury, and RC Zangar. 2004. "A Protein Microarray ELISA for Screening Biological Fluids." Chapter 14 in Protein arrays : methods and protocols (Methods in Molecular Biology), vol. 264, ed. Eric Fung, pp. 161-172.  Humana Press, Totowa, NJ. 
  • Zangar RC, YY Fan, and RS Chapkin. 2004. "Interactions of phospholipase D and cytochrome P450 protein stability ." Biochemical Pharmacology 68(3):503-512. 
  • Chen WNU, RL Woodbury, LE Kathmann, L Opresko, RC Zangar, HS Wiley, and BD Thrall. 2004. "Induced autocrine signaling through the epidermal growth factor receptor contributes to the response of mammary epithelial cells to tumor necrosis factor alpha." Journal of Biological Chemistry 279(18):18488-18496. 
  • Zangar RC, SM Varnum, CY Covington, and RD Smith. 2004. "A rational approach for discovering and validating cancer markers in very small samples using mass spectrometry and ELISA microarrays." Disease Markers 20(3):135-148. 
  • Zangar RC, DR Davydov, and S Verma. 2004. "Mechanisms that Regulate Production of Reactive Oxygen Species by Cytochrome P450 ." Toxicology and Applied Pharmacology 199(3):316-331. 
  • Zangar RC, DR Davydov, and S Verma. 2004. "Mechanisms that regulate production of reactive oxygen species by cytochrome P450." Toxicology and Applied Pharmacology 199(3):316-331.  doi:10.1016/j.taap.2004.01.018

2003

  • Zangar RC, TA Kocarek, S Shen, N Bollinger, MS Dahn, and DW Lee. 2003. "Suppression of Cytochrome P450 3A Protein Levels by Proteasome Inhibitors ." Journal of Pharmacology and Experimental Therapeutics 305(3):872-879.  doi:10.1124/jpet.102.044628
  • Zangar RC, TA Kocarek, S Shen, N Bollinger, MS Dahn, and DW Lee. 2003. "Suppression of cytochrome P450 3A protein levels by proteasome inhibitors." Journal of pharmacology and experimental therapeutics 305(3):872-879. 
  • Kimzey AL, KK Weitz, FP Guengerich, and RC Zangar. 2003. "Hydroperoxy-10,12-octadecadienoic acid stimulates cytochrome P450 3A protein aggregation by a mechanism that is inhibited by substrate." Biochemistry 42(43):12691-12699. 
  • Varnum SM, CC Covington, RL Woodbury, K Petritis, LJ Kangas, MS Abdullah, JG Pounds, RD Smith, and RC Zangar. 2003. "Proteomic Characterization of Nipple Aspirate Fluid: Identification of Potential Biomarkers of Breast Cancer ." Breast Cancer Research and Treatment 80(1):87-97. 
  • Varnum SM, CC Covington, RL Woodbury, K Petritis, LJ Kangas, MS Abdullah, JG Pounds, RD Smith, and RC Zangar. 2003. "Proteomic Characterization of Nipple Aspirate Fluid: Identification of Potential Biomarkers of Breast Cancer." Breast Cancer Research and Treatment 80(1):87-97. 
  • Varnum SM, CC Covington, RL Woodbury, K Petritis, LJ Kangas, MS Abdullah, JG Pounds, RD Smith, and RC Zangar. 2003. "Proteomic characterization of nipple aspirate fluid: Identification of potential biomarkers of breast cancer." Breast Cancer Research and Treatment 80(1):87-97.  doi:10.1023/A:1024479106887

2002

  • Zangar RC, AL Kimzey, JR Okita, DS Wunschel, RJ Edwards, H Kim, and RT Okita. 2002. "Cytochrome P450 3A Conjugation to Ubiquitin in a Process Distinct from Classical Ubiquitination Pathway." Molecular Pharmacology 61(4):892-904. 
  • Zangar RC, AL Kimzey, JR Okita, DS Wunschel, RJ Edwards, HS Kim, and RT Okita. 2002. "Cytochrome P450 3A conjugation to ubiquitin in a process distinct from classical ubiquitination pathway." Molecular Pharmacology 61:892-904. 
  • Woodbury RL, SM Varnum, and RC Zangar. 2002. "Elevated HGF Levels in Sera from Breast Cancer Patients Detected Using a Protein Microarray ELISA." Journal of Proteome Research 2002(1):233-237. 

2001

  • Kim H, DA Putt, RC Zangar, CR Wolf, FP Guengerich, RJ Edwards, PF Holllenberg, and RF Novak. 2001. "Differential Induction of Rat Hepatic Cytochromes P450 3A1, 3A2, 2B1, 2B2, and 2E1 in Response to Pyridine Treatment. ." Drug Metabolism and Disposition 29(3):353-360. 
  • Springer DL, RC Zangar, KL Wahl, KK Wong, and KD Rodland. 2001. "Proteomic Analysis of Changes in Protein Tyrosine Phosphorylation in Transformed Cells after Treatment with a Novel Chemotherapeutic, Carboxyamidotriazole." Toxicological Sciences 60(1):139. 

2000

  • Zangar RC, JM Benson, VL Burnett, and DL Springer. 2000. "Cytochrome P450 2E1 is the Primary Enzyme Responsible for Low-Dose Carbon Tetrchloride Metabolism in Human Liver Microsomes ." Chemico-Biological Interactions 125(3):233-43. 
  • Cummings BS, RC Zangar, RF Novak, and LH Lash. 2000. "Cytotoxicity of trichloroethylene and S-(1, 2-dichlorovinyl)-L-cysteine in primary cultures of rat renal proximal tubular and distal tubular cells." Toxicology 150(1-3):83-98. 
  • Kocarek TA, RC Zangar, and RF Novak. 2000. "Post-transcriptional regulation of rat CYP2E1 expression: role of CYP2E1 mRNA untranslated regions in control of translational efficiency and message stability. ." Archives of Biochemistry and Biophysics 376(1):180-190. 
  • Thrall KD, ME Vucelick, RA Gies, RC Zangar, KK Weitz, TS Poet, DL Springer, DM Grant, and JM Benson. 2000. "Comparative Metabolism of Carbon Tetrachloride in Rats, Mice and Hamsters Using Gas Uptake and PBPK Modeling." Journal of Toxicology and Environmental Health 60(8):531-548. 

1999

  • Zangar RC, JR Okita, K Hyesook, PE Thomas, A Anderson, RJ Edwards, DL Springer, and RT Okita. 1999. "Effect of Calcium Channel Antagonists Nifedipine and Nicardipine on Rat Cytochrome P450 2B and 3A Forms ." Journal of pharmacology and experimental therapeutics 290(3):1436-41. 

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