Proteomedix Frontiers


Literature: Please find below the list of current scientific publications available to better understand this outstanding technology

Publicationlist of Quantitative Targeted Absolute Proteomics (QTAP) Research-1


Updated at April 1, 2016



I. Review, Perspective andBook Chapter

1.    S. Ohtsuki, Y. Uchida, Y. Kubo and T. Terasaki, Quantitative targeted absolute proteomics-basedADME research as a new path to drug discovery and development: Methodology,Advantages, Strategy and Prospects. J. Pharm. Sci.,100 (9): 3547-3559(2011). Free Download

2.    OhtsukiS, Hirayama M, Ito S, Uchida Y, Tachikawa M, Terasaki T., Quantitative targetedproteomics for understanding the blood-brain barrier: towardspharmacoproteomicsExpert RevProteomics. 11(3):303-313 (2014).

3.    MTachikawa, Y. Uchida, S. Ohtsuki and T. Terasaki, Recent progress in blood-brain barrier and blood-CSF barrier transportresearch: Pharmaceutical relevance for drug delivery to the brain. “Drug Delivery to theBrain – Physiological Concepts, Methodologies and Approaches”, ed., by R. Thorne,L. de Lange, M. Hammarlund-Udenaes, springer, pp 23-62 (2014).

4.    Y. Uchida, M. Tachikawa, S. Ohtsuki and T. Terasaki, Blood-brain barrier (BBB)pharmacoproteomics: a new research field opened up byquantitative targeted absolute proteomics (QTAP). “Drug Delivery to theBrain – Physiological Concepts, Methodologies and Approaches”, ed., by R. Thorne,L. de Lange, M. Hammarlund-Udenaes, springer, pp 63-100 (2014).


II. Method Development

5.    J. Kamiie, S. Ohtsuki, R. Iwase, K. Ohmine, Y. Katsukura, K. Yanai, Y. Sekine, Y. Uchida, S. Ito, T. Terasaki, Quantitative atlas of membrane transporter proteins: Development andapplication of a highly sensitive simultaneous LC/MS/MS method combined withnovel in-silico peptide selection criteria. Pharm. Res., 25: 1469-1483(2008). (Selected for 2010 AAPS Meritorious Manuscript Award for theOutstanding Paper)


III. Protocol

6.    Uchida Y., Tachikawa M., Obuchi W., Hoshi Y., Tomioka Y., Ohtsuki S., TerasakiT., A Study Protocol for Quantitative TargetedAbsolute Proteomics (QTAP) by LC-MS/MS: Application for Inter-StrainDifferences in Protein Expression Levels of Transporters, Receptors, Claudin-5,and Marker Proteins at the Blood-Brain Barrier in ddY, FVB, and C57BL/6J mice. Fluids and Barriersof the CNS, 10: 21 (2013) Free Article (Open Access Journal)


IV. Validation

7.    Sakamoto A., MatsumaruT., Ishiguro N., Schaefer O., Ohtsuki S., Inoue T., Kawakami H., Terasaki T., Reliability and robustness ofsimultaneous absolute quantification of drug transporters, cytochrome P450enzymes and UDP-glucuronosyltranferases in human liver tissue by multiplexed MRM/SRM mode tandem massspectrometry with nano-liquid chromatography (Nano-LC-MS/MS).J. Pharm. Sci., 100 (9): 4037-4043(2011). Free Download


. Applications

< Basic Research >

1) Transporter Protein Quantification

8.   Niessen J, Jedlitschky G, Grube M, Bien S, Schwertz H,Ohtsuki S, KawakamiH, Kamiie J, Oswald S, Starke K, Strobel U, Siegmund W, Rosskopf D, Greinacher A, Terasaki T, KroemerHK, Human platelets express organic anion-transporting peptide 2B1, an uptaketransporter for atorvastatin.Drug MetabDispos., 37(5):1129-1137 (2009).

9.   Niessen J, Jedlitschky G, Grube M, KawakamiH, Kamiie J,Ohtsuki S, Schwertz H, Bien S, Starke K, Ritter C, Strobel U,Greinacher A, Terasaki T, KroemerHK., Expression of ABC-type transport proteins in human platelets. Pharmacogenet. Genomics, 20(6):396-400 (2010).

10.   Ito K, Uchida Y, Ohtsuki S, Aizawa S, KawakamiH, KatsukuraY, Kamiie J, Terasaki T., Quantitative membrane protein expression at theblood-brain barrier of adult and youngercynomolgus monkeys. J. Pharm. Sci., 100 (9): 3939-3950 (2011).    


2) Analysis of Membrane Protein Localization

11.   Kubo Y., Ohtsuki S., Uchida Y. and Terasaki T.,Quantitative determination of luminal and abluminal membranedistributions of transporters in porcine brain capillaries by plasma membranefractionation and quantitative targeted proteomics. J Pharm Sci., 104(9): 3060-3068 (2015).DOI:10.1002/jps.24398 (2015). Free Download

  1. Uchida Y, Toyohara T, Ohtsuki S, Moriyama Y, Abe T andTerasaki T, Quantitative targeted absolute proteomics for 28 transporters in brush-border and basolateral membrane fractions of rat kidney, J Pharm Sci., 105: 1011-1016 (2016).Free Download


3) CYP Protein Quantification

13.    Kawakami H, Ohtsuki S, Kamiie J, Suzuki T, Abe T, TerasakiT,Simultaneous absolute quantification of 11 cytochrome P450 isoforms in humanliver microsomes by liquid chromatography tandem mass spectrometry with in silicotargetpeptide selection. J. Pharm.Sci., 100: 341-352 (2011).

Applied Research >

4) Characterization of Human Blood-Brain Barrier, Blood-CSFBarrier, Liver and Lung

14.        Uchida Y, Ohtsuki S, Katsukura Y, Ikeda C,Suzuki T, KamiieJ, Terasaki T., Quantitative targeted absolute proteomics of humanblood-brain barrier transporters and receptors. J.Neurochem., 117(2): 333-345 (2011).

15.       Shawahna R, Uchida Y, Decleves X, Ohtsuki S, Yousif S,Dauchy S, Jacob A, Chassoux F, Daumas C, Couraud PO,Terasaki T, Scherrmann JM.,Transcriptomic and quantitative proteomic analysis of transporters and drugmetabolizing enzymes in freshly isolated human brain microvesselsMol. Pharm., 8(4): 1332-1341 (2011). 

16.       Hoshi Y, Uchida Y, Tachikawa M, Inoue T, Ohtsuki S andTerasaki T,Quantitative atlas of blood–brain barrier transporters, receptors, and tightjunction proteins in rats and common marmoset. J Pharm Sci., 102 (9): 3343-3355 (2013). Free Download

17.       Ohtsuki S, SchaeferO, Kawakami H, Inoue T, Liehner S, Sato A, Ishiguro N, Kishimoto W, Ludwig-Schwellinger E, Ebner T, and Terasaki T.,Simultaneous absolute protein quantification of transporters, Cytochrome P450sand UDP-glucuronosyltransferases as a novel approach for the characterizationof individual human liver: Comparison with mRNA levels and activities. Drug MetabDispos., 40(1):83-92 (2012).

18.       Sakamoto A, Matsumaru T, Yamamura N, Uchida Y,Tachikawa M, Ohtsuki S. and Terasaki T,Quantitative Expression of Human Drug Transporter Proteins in Lung Tissues:Analysis of Regional, Gender and Inter-individual differences by LiquidChromatography-Tandem Mass Spectrometry. J Pharm Sci., 102 (9): 3395-3406 (2013).Free Download

19.       Kaneko Y., Tachikawa M., Akaogi R., Fujimoto K., Ishibashi M., Uchida Y., Couraud P.O., Ohtsuki S., Hosoya K., TerasakiT.,Contribution of pannexin 1 and connexin 43 hemichannelsto extracellular calcium-dependent transport dynamics inhuman blood–brain barrier endothelial cells. JPharmacolExpTher353(1):192-200 (2015).

20.       Sakamoto A., Matsumaru T., Yamamura N., Suzuki S., Uchida Y., Tachikawa M., and Terasaki T., Drugtransporter protein quantification of immortalized human lung cell linesderived from tracheo-bronchial epithelial cells (Calu-3 and BEAS2-B),bronchiolar-alveolar cells (NCI-H292 and NCI-H441) and alveolar type II-likecells (A549) by liquid chromatography-tandem mass spectrometry. J Pharm Sci.,104(9): 3029-3038 (2015).Free Download

21.       Uchida Y, Ito K, Ohtsuki S, Kubo Y, Suzuki T and Terasaki T, Majorinvolvement of Na+-dependent multivitamin transporter (SLC5A6/SMVT) in uptakeof biotin and pantothenic acid by human brain capillary endothelial cells. Neurochem.,134(1): 97-112 (2015). doi:10.1111/jnc.13092

22.       Uchida Y, Zhang Z, Tachikawa M and Terasaki T,Quantitative Targeted Absolute Proteomics of Rat Blood-Cerebrospinal FluidBarrier Transporters: Comparison with a Human Specimen, J Neurochem., 134(6):1104-1115 (2015).

23.       Sakamoto A, Suzuki S, Matsumaru T, YamamuraN, Uchida Y, Tachikawa M and Terasaki T,Correlation of OCTN1 and MRP1 transport activities with protein expressionlevels in primary cultured human tracheal, bronchial and alveolar epithelialcells, J Pharm Sci., 105: 876-883 (2016).  doi: 10.1002/jps.24661 Free Download

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