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Masaru Miyagi, PhD

Masaru Miyagi, PhD

Associate Professor 216-368-5917 (o)

Dr. Miyagi received his Ph.D. degree in Biochemistry from the Osaka University (Osaka, Japan) in 1997. He joined Case Western Reserve University in 2006 as an Assistant Professor. Before joining the University, Dr. Miyagi worked for Takara Shuzo Co. Ltd. as a research scientist, Cleveland Clinic Foundation as a post-doctoral fellow, and the University of North Dakota as an Assistant Professor. Dr. Miyagi is an expert in protein analysis. He has developed several mass spectrometry methods for proteome characterization and protein structural analysis and successfully applied the developed methods to answer a range of important biological questions. Dr. Miyagi has published more than 90 peer-reviewed journal articles, reviews, and book chapters and holds five patents. Those publications have been cited more than 4800 times. Dr. Miyagi teaches two core courses in the systems biology and bioinformatics graduate program and the co-director of the MS graduate program.

NCBI Bibliography

We are motivated to develop analytical methods for proteome profiling and protein structural characterization. Mass spectrometry is the pre-eminent technology in analytical protein chemistry. However, current methods on the front end of mass spectrometry analysis are not fully utilizing the potential of modern mass spectrometry technologies. Development of advanced analytical methods on the front end of mass spectrometry analysis is, therefore, important to advancing the study of proteins. The followings are some of the methodologies developed in my lab: 1) proteolytic 18O labeling to measure the protein abundance in proteome samples, 2) histidine hydrogen-deuterium exchange mass spectrometry (His-HDX-MS) to probe protein structural changes, 3) 13C6-Lys labeling of C. elegans to study the proteome dynamics of this model organism, 4) single-tube shotgun proteomics methods that uses all volatile chemicals, and 5) 13C labeling of lysine acetyl groups to determine the extent of lysine acetylation at individual sites. We are currently focused on developing a method for identifying protein targets of drugs in cell lysates. It is essential to identify a drug's target(s) to better understand the mechanism of action and anticipate possible side effects. 

Recent Publications

1.            Berthiaume, J. M., Hsiung, C. H., Austin, A. B., McBrayer, S. P., Depuydt, M. M., Chandler, M. P., Miyagi, M., and Rosca, M. G. (2017) Methylene blue decreases mitochondrial lysine acetylation in the diabetic heart. Mol Cell Biochem. 10.1007/s11010-017-2993-1

2.            Mamillapalli, S., Miyagi, M., and Bann, J. G. (2017) Stability of domain 4 of the anthrax toxin protective antigen and the effect of the VWA domain of CMG2 on stability. Protein Sci. 26, 355–364

3.            Yamada, K. D., Omori, S., Nishi, H., and Miyagi, M. (2017) Identification of the sequence determinants of protein N-terminal acetylation through a decision tree approach. BMC Bioinformatics. 18, 289

4.            Alagramam, K. N., Gopal, S. R., Geng, R., Chen, D. H., Nemet, I., Lee, R., Tian, G., Miyagi, M., Malagu, K. F., Lock, C. J., Esmieu, W. R., Owens, A. P., Lindsay, N. A., Ouwehand, K., Albertus, F., Fischer, D. F., Burli, R. W., MacLeod, A. M., Harte, W. E., Palczewski, K., and Imanishi, Y. (2016) A small molecule mitigates hearing loss in a mouse model of Usher syndrome III. Nat Chem Biol. 12, 444–451

5.            Miyagi, M., and Kasumov, T. (2016) Monitoring the synthesis of biomolecules using mass spectrometry. Philos Trans A Math Phys Eng Sci. 10.1098/rsta.2015.0378

6.            Zhang, S., Gu, H., Chen, H., Strong, E., Ollie, E. W., Kellerman, D., Liang, D., Miyagi, M., Anderson, V. E., Piccirilli, J. A., York, D. M., and Harris, M. E. (2016) Isotope effect analyses provide evidence for an altered transition state for RNA 2’-O-transphosphorylation catalyzed by Zn(2.). Chem Commun. 52, 4462–4465

7.            Ahmad, M. F., Huff, S. E., Pink, J., Alam, I., Zhang, A., Perry, K., Harris, M. E., Misko, T., Porwal, S. K., Oleinick, N. L., Miyagi, M., Viswanathan, R., and Dealwis, C. G. (2015) Identification of Non-nucleoside Human Ribonucleotide Reductase Modulators. J Med Chem. 58, 9498–9509

8.            Salom, D., Cao, P., Yuan, Y., Miyagi, M., Feng, Z., and Palczewski, K. (2015) Isotopic labeling of mammalian G protein-coupled receptors heterologously expressed in Caenorhabditis elegans. Anal Biochem. 472, 30–36

9.            Vazquez, E. J., Berthiaume, J. M., Kamath, V., Achike, O., Buchanan, E., Montano, M. M., Chandler, M. P., Miyagi, M., and Rosca, M. G. (2015) Mitochondrial complex I defect and increased fatty acid oxidation enhance protein lysine acetylation in the diabetic heart. Cardiovasc Res. 107, 453–465

10.          Vukoti, K., Yu, X., Sheng, Q., Saha, S., Feng, Z., Hsu, A. L., and Miyagi, M. (2015) Monitoring newly synthesized proteins over the adult life span of Caenorhabditis elegans. J Proteome Res. 14, 1483–1494

11.          Blankenship, E., Vukoti, K., Miyagi, M., and Lodowski, D. T. (2014) Conformational flexibility in the catalytic triad revealed by the high-resolution crystal structure of Streptomyces erythraeus trypsin in an unliganded state. Acta Crystallogr D Biol Crystallogr. 70, 833–840

12.          Chadegani, F., Lovell, S., Mullangi, V., Miyagi, M., Battaile, K. P., and Bann, J. G. (2014) (19)F nuclear magnetic resonance and crystallographic studies of 5-fluorotryptophan-labeled anthrax protective antigen and effects of the receptor on stability. Biochemistry. 53, 690–701

13.          Guo, Y., Miyagi, M., Zeng, R., and Sheng, Q. (2014) O18Quant: a semiautomatic strategy for quantitative analysis of high-resolution 16O/18O labeled data. Biomed Res Int. 2014, 971857

14.          Hayashi, N., Kuyama, H., Nakajima, C., Kawahara, K., Miyagi, M., Nishimura, O., Matsuo, H., and Nakazawa, T. (2014) Imidazole C-2 hydrogen/deuterium exchange reaction at histidine for probing protein structure and function with matrix-assisted laser desorption ionization mass spectrometry. Biochemistry. 53, 1818–1826

15.          Mullangi, V., Mamillapalli, S., Anderson, D. J., Bann, J. G., and Miyagi, M. (2014) Long-range stabilization of anthrax protective antigen upon binding to CMG2. Biochemistry. 53, 6084–6091

16.          Gu, H., Zhang, S., Wong, K. Y., Radak, B. K., Dissanayake, T., Kellerman, D. L., Dai, Q., Miyagi, M., Anderson, V. E., York, D. M., Piccirilli, J. A., and Harris, M. E. (2013) Experimental and computational analysis of the transition state for ribonuclease A-catalyzed RNA 2’-O-transphosphorylation. Proc Natl Acad Sci U S A. 110, 13002–13007

17.          Kohno, H., Chen, Y., Kevany, B. M., Pearlman, E., Miyagi, M., Maeda, T., Palczewski, K., and Maeda, A. (2013) Photoreceptor proteins initiate microglial activation via Toll-like receptor 4 in retinal degeneration mediated by all-trans-retinal. J Biol Chem. 288, 15326–15341

18.          Su, Y. T., Gao, C., Liu, Y., Guo, S., Wang, A., Wang, B., Erdjument-Bromage, H., Miyagi, M., Tempst, P., and Kao, H. Y. (2013) Monoubiquitination of filamin B regulates vascular endothelial growth factor-mediated trafficking of histone deacetylase 7. Mol Cell Biol. 33, 1546–1560

19.          Sun, Q. A., Wang, B., Miyagi, M., Hess, D. T., and Stamler, J. S. (2013) Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor/Ca2+ release channel (RyR1): sites and nature of oxidative modification. J Biol Chem. 288, 22961–22971

20.          Wanner, J., Subbaiah, R., Skomorovska-Prokvolit, Y., Shishani, Y., Boilard, E., Mohan, S., Gillespie, R., Miyagi, M., and Gobezie, R. (2013) Proteomic profiling and functional characterization of early and late shoulder osteoarthritis. Arthritis Res Ther. 15, R180

21.          Wei, H., Wang, B., Miyagi, M., She, Y., Gopalan, B., Huang, D. B., Ghosh, G., Stark, G. R., and Lu, T. (2013) PRMT5 dimethylates R30 of the p65 subunit to activate NF-kappaB. Proc Natl Acad Sci U S A. 110, 13516–13521

22.          Kadiyala, C. S., Zheng, L., Du, Y., Yohannes, E., Kao, H. Y., Miyagi, M., and Kern, T. S. (2012) Acetylation of retinal histones in diabetes increases inflammatory proteins: effects of minocycline and manipulation of histone acetyltransferase (HAT) and histone deacetylase (HDAC). J Biol Chem. 287, 25869–25880

23.          Mullangi, V., Zhou, X., Ball, D. W., Anderson, D. J., and Miyagi, M. (2012) Quantitative measurement of the solvent accessibility of histidine imidazole groups in proteins. Biochemistry. 51, 7202–7208

24.          Orban, T., Jastrzebska, B., Gupta, S., Wang, B., Miyagi, M., Chance, M. R., and Palczewski, K. (2012) Conformational dynamics of activation for the pentameric complex of dimeric G protein-coupled receptor and heterotrimeric G protein. Structure. 20, 826–840

25.          Rao Kadiyala, C. S., Mullangi, V., Zhou, X., Vukoti, K. M., and Miyagi, M. (2012) Rapid and effective removal of perfluorooctanoic acid from proteomics samples. Proteomics. 12, 2271–2275

26.          Sun, Q. A., Hess, D. T., Wang, B., Miyagi, M., and Stamler, J. S. (2012) Off-target thiol alkylation by the NADPH oxidase inhibitor 3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine (VAS2870). Free Radic Biol Med. 52, 1897–1902

27.          Yuan, Y., Kadiyala, C. S., Ching, T. T., Hakimi, P., Saha, S., Xu, H., Yuan, C., Mullangi, V., Wang, L., Fivenson, E., Hanson, R. W., Ewing, R., Hsu, A. L., Miyagi, M., and Feng, Z. (2012) Enhanced energy metabolism contributes to the extended life span of calorie-restricted Caenorhabditis elegans. J Biol Chem. 287, 31414–31426

Book Chapters

1.            Miyagi, M. (2017) Site-Specific Quantification of Lysine Acetylation Using Isotopic Labeling. in Methods Enzymol, Proteomics (Shukla, A. K. ed), pp. 85–95, Academic Press, 586, 85–95

2.            Miyagi, M. (2017) Monitoring Protein Synthesis in Caenorhabditis elegans Using SILAC. in Methods Enzymol, Proteomics (Shukla, A. K. ed), pp. 77–89, 585, 77–89

3.            Lodowski, D. T., and Miyagi, M. (2015) Analysis of conformational changes in rhodopsin by histidine hydrogen-deuterium exchange. in Methods Mol Biol, 2015/02/24, pp. 123–132, 1271, 123–132

4.            Chance, M. R., Chang, J., Schlatzer, D., and Miyagi, M. (2009) Quantitative Proteomics. in Encyclopedia of Analytical Chemistry (Meyers, R. A. ed), pp. 1–23, 10.1002/9780470027318.a9019


1.           U.S. Patent 6,194,190 (Issued February 27, 2001), titled “Amino-terminal deblocking enzyme”, Inventors: Yukiko Izu, Tetsuki Tanaka, Masaru Miyagi, Tetsuo Tanigawa, Jun Tomono, Susumu Tsunasawa, Ikunoshin Kato

2.           U.S. Patent 7,476,546 (Issued January 13, 2009), titled “Method for single oxygen atom incorporation into digested peptides using peptidases”, Inventors: Masaru Miyagi and K. C. Sekhar Rao

3.           U.S. Patent 8,580,534 (Issued November 12, 2013), titled “Method for incorporation of two oxygen atoms into digested peptides using peptidases”, Inventors: Masaru Miyagi

4.           U.S. Patent 8,921,515 B2 (Issued December 30, 2015), titled “Methods and compositions of preparation for proteome analysis”, Inventors: Masaru Miyagi and Chandra Sekhar Rao Kadiyala



SYBB 555: Current Proteomics

This course is designed for graduate students across the university who wish to acquire a better understanding of fundamental concepts of proteomics and hands-on experience with techniques used in current proteomics.  Lectures will cover protein/peptide separation techniques, protein mass spectrometry, bioinformatics tools, and biological applications which include quantitative proteomics, protein modification proteomics, interaction proteomics, structural genomics and structural proteomics.  Laboratory portion will involve practice on the separation of proteins by two-dimensional gel electrophoresis, molecular weight measurement of proteins by mass spectrometry, peptide structural characterization by tandem mass spectrometry and protein identification using computational tools.  The instructors' research topics will also be discussed. Recommended preparation: CBIO 453 and CBIO 455. 

SYBB 311/411A: Survey of Bioinformatics: Technologies in Bioinformatics

SYBB 311/411A is a 5-week course that introduces students to the high-throughput technologies used to collect data for bioinformatics research in the fields of genomics, proteomics, and metabolomics. In particular, we will focus on mass spectrometer-based proteomics, DNA and RNA sequencing, genotyping, protein microarrays, and mass spectrometry-based metabolomics. This is a lecture-based course that relies heavily on out-of-class readings. Graduate students will be expected to write a report and give an oral presentation at the end of the course.

SYBB 311/411A is part of the SYBB survey series which is composed of the following course sequence: (1) Technologies in Bioinformatics, (2) Data Integration in Bioinformatics, (3) Translational Bioinformatics, and (4) Programming for Bioinformatics. Each standalone section of this course series introduces students to an aspect of a bioinformatics project - from data collection (SYBB 311/411A), to data integration (SYBB 311/411B), to research applications (SYBB 311/411C), with a fourth module (SYBB 311/411D) introducing basic programming skills.

Graduate students have the option of enrolling in all four courses or choosing the individual modules most relevant to their background and goals with the exception of SYBB411D, which must be taken with SYBB411A.

Offered as SYBB 311A, BIOL 311A and SYBB 411A.

BIOC 430: Advanced Methods in Structural Biology

The course is designed for graduate students who will be focusing on one or more methods of structural biology in their thesis project. This course is divided into 3-6 sections (depending on demand). The topics offered will include X-ray crystallography, nuclear magnetic resonance spectroscopy, optical spectroscopy, mass spectrometry, cryo-electron microscopy, and computational and design methods. Students can select one or more modules. Modules will be scheduled so that students can take all the offered modules in one semester. Each section is given in 5 weeks and is worth 1 credit. Each section covers one area of structural biology at an advanced level such that the student is prepared for graduate level research in that topic.

Offered as BIOC 430, CHEM 430, PHOL 430, and PHRM 430.

Current Grant Support:

Mitsubishi-Tanabe Pharma, Miyagi (PI), 07/17-06/18, 0.9 calendar
Identifying protein targets
Role: PI

R01GM096000, Harris (PI), 05/14-04/18, 0.6 calendar
Mechanistic Enzymology of Phosphoryl Transfer Enzymes
Role: Co-Investigator

R01HL098217, Nieman (PI), 04/16-03/21, 1.2 calendar
The Role of Protease Activated Receptors on Platelets
Role: Co-Investigator

Past Grant Support:
NIH-NCI, R21-CA160060, Wang and Ewing (PI), 09/12-08/14, 0.6 calendar
Developing Novel Technology for Mapping Dynamic Oncoprotein Interaction Network
Role: Co-Investigator

Usher III Initiative, Inc., Imanishi (PI), 11/12-10/13, 1.2 calendar
Characterization of Clrn1 and Usher syndrome type III in the eye
Role: Co-Investigator

NIH/NIBIB, R01-EB009688, Chance (PI), 04/10-03/15, 1.2 calendar
Radiolytic Footprinting Methods for Structural Mass Spectrometry
Role: Co-Investigator

NIH/NEI, R21-EY021595, Miyagi and Kern (PI), 01/2012-12/2013, 3.6 calendar
Global Characterization of Lysine Acetylation in Diabetic Retina
Role: PI

NIH/NIDDK, P20DK090871, Daneshgari (PI), 9/10-7/12, 0.9 calendar
Urological Complications of Obesity and Diabetes
Role: Co-Investigator

NIH/NEI, P30-EY11373, Pearlman (PI), 1/07-3/12, 0.6 calendar
Core Grant for Vision Research
Role: Proteomic Core Facility Co-Director

JDRF, Kern (PI), 09/01/2009-08/31/2011, 1.2 calendar
Interconnecting pathways of VEGF signaling in diabetic kidney and retina
Role: Co-Investigator

B.S., Biochemistry
University of the Ryukyus, Okinawa, Japan

M.S., Biochemistry
University of the Ryukyus, Okinawa, Japan

Ph.D., Biochemistry (Awarded in 1997)
Osaka University, Osaka, Japan