Kazuhiro Yamada
Dr
Ann Arbor,MI
Summary
An innovative and tenacious life scientist with a proven track record of tackling challenging research topics. Possess strong problem-solving skills and have the ability to be productive. Driven by a strong desire to transition into the biotech industry to explore new career opportunities and contribute to cutting-edge advancements.
Overview
32
32
years of professional experience
9
9
years of post-secondary education
Work History
Research Lab Specialist Senior
University of Michigan
09.2017 - 08.2024
- Determined the crystal structures of a multi-domain protein, vitamin B12-dependent methionine synthase, and identified all its conformations, thereby bringing the project to a significant milestone
- Visualized protein conformational changes during the allosteric transition of methylenetetrahydrofolate reductase (MTHFR) induced by the allosteric inhibitor S-adenosylmethionine, using X-ray crystallography
- Solved the crystal structure of MTHFR in complex with a substrate analogue and proposed a rearrangement of amino acid residues in the active site during catalysis
- Identified ten phosphorylation sites on MTHFR through top-down proteomics using LC-MS
- Conducted analysis of partner proteins associated with a cellular B12 transport protein using biotin proximity labeling and LC-MS-based bottom-up proteomics
Research Associate
Uniformed Services University
01.2012 - 08.2017
- Determined the crystal structures of methionine synthase, a multi-domain protein, in multiple conformations, capturing three of the four proposed states as evidence of the massive domain motion in its catalytic cycle
- Crystalized and solved the crystal structure of MMADHC, a cellular B12 transport protein, using high-throughput screening
- Demonstrated how mercaptopyruvate sulfurtransferase binds its substrate and proposed the reaction mechanism within the active site
- Perform crystallization of the Protein
- RNA complex using high-throughput screening method and automated liquid handling systems
Researcher
Tokyo University of Agriculture
01.2011 - 01.2012
- Reported the effects of maternal B12 on offspring testis development, highlighting the importance of maternal protein nutrition, particularly methionine content and biosynthesis, for healthy testis development in neonates
Associate Professor
Tokyo University of Agriculture and Technology
04.2006 - 03.2011
- Characterized the biochemical properties of 22 rare MTHFR patient mutants, enabling the classification of mutations and predicting the effectiveness of vitamin B2 and folic acid treatment for patients
- Developed a high-throughput screening method for MTHFR kinases using commercially available compound libraries and conducted kinase identification based on screening results using protein labeling agents and LC-MS
- Explained how patient mutations influence enzyme properties using thermophilic MTHFR, providing insights into the structural basis of these mutations
- Cloned hybridomas and performed epitope mapping for the development of sandwich ELISA and immunochromatography assays
Research Investigator
University of Michigan
04.1999 - 03.2006
- Developed a high-level heterologous expression system for human MTHFR using the baculovirus-insect cell expression system and successfully elucidated the effects of the common 677C->T polymorphism on MTHFR activity, as well as the protective roles of B2 and folic acid against the patient mutant enzyme
- Investigated the effect of protein phosphorylation on the allosteric regulation of MTHFR and found that S-adenosylmethionine dual-regulates MTHFR, acting both as an allosteric ligand and as a modulator promoting the enzyme's post-translational modification
- Examined the biochemical role of the MTRR gene product in the stabilization of the methionine synthase apoenzyme, holoenzyme formation, and holoenzyme reactivation, and concluded that MTRR acts as a specific molecular chaperone for methionine synthase
Postdoctoral Fellow
Okayama University
10.1998 - 03.1999
- Demonstrated how B12 analogues function as cofactors for methionine synthase, elucidating the enzyme's efficient use of the natural form of B12
Research Assistant
Tokyo University of Agriculture
04.1992 - 03.1995
- Established a B12-deficient rat model, which appears to be useful for studying male infertility due to severe testicular damage
- Confirmed that testicular damage in B12-deficient rats can be significantly alleviated by adding methionine to the diet, suggesting that MTHFR, methionine synthase, and methionine adenosyltransferase are involved in this process
- Purified methionine adenosyltransferase from rat liver to homogeneity, then prepared antiserum against the enzyme by immunizing a rabbit with the purified protein
- Measured methionine adenosyltransferase activity in the liver of B12-deficient rats and observed a decrease in both enzyme activity and quantity, correlating with the reduced activity of B12-dependent methionine synthase
Education
Ph.D. - Engineering (Biological Sciences)
Okayama University
Okayama, Japan 04.1995 - 09.1998
M.S. - Agricultural Chemistry (Nutritional Science)
Tokyo University of Agriculture
Tokyo, Japan 04.1990 - 03.1992
B.S. - Agricultural Chemistry (Nutritional Science)
Tokyo University of Agriculture
Tokyo, Japan 04.1986 - 03.1990
Skills
- Protein biochemistry
- Recombinant protein expression
- Protein characterization
- Molecular and cell biology techniques
- Structural biology
- Bioinformatics
Publications
- total 26, *corresponding author
- (preprint) Mendoza, J., Yamada, K.*, Castillo, C., Wilhelm, C. A., Koutmos, M.* (2025 preprint biorxiv) https://doi.org/10.1101/2024.08.29.610163
- Yamada, K.*, Mendoza, J., Koutmos, M.* (2024) Nat Commun. 15(1):5167
- Mendoza, J., Purchal, M., Yamada, K.*, Koutmos, M.* (2023) Nat Commun. 14(1):6365.
- Yamada, K.*, Mendoza, J., Koutmos, M*. (2023) J Biol Chem. 299(2), 102855
- Yamada, K., Gherasim, C., Banerjee, R.*, and Koutmos, M.* (2015) J Biol Chem. 290(49), 29155-29166
- Yamada, K.*, Gravel, R. A., Toraya, T., and Matthews, R. G*. (2006) PNAS. 103(25), 9476-9481
- Yamada, K.*, Strahler, J. R., Andrews, P. C., and Matthews, R. G*. (2005) PNAS. 102 (30), 10454-10459
- Yamada, K., Chen, Z., Rozen, R., and Matthews, R. G*. (2001) PNAS. 98(26), 14853-14858
- Yamada, K., Kawata, T., Wada, M, Isshiki, T., Onoda, J., Kawanishi, T., Kunou, A., Tadokoro, T., Tobimatsu, T., Maekawa, A. and Toraya, T*. (2000) J Nutr. 130(8), 1894-1900
- Yamada, K., Yamada, S., Tobimatsu, T. and Toraya, T*. (1999) J Biol Chem. 274 (50), 35571-35576
Skills
Protein biochemistry, Molecular biology and cell biology, Structural biology, top-down and bottom-up LC-MS based proteomics, in vivo skills, Common essential tools and skills, Strong research laboratory skills, Basic analytical and problem-solving skills, Oral and written communication skills, General interpersonal and communication skills, Computer: Linux, Windows, and Mac
Timeline
Research Lab Specialist Senior
University of Michigan
09.2017 - 08.2024
Research Associate
Uniformed Services University
01.2012 - 08.2017
Researcher
Tokyo University of Agriculture
01.2011 - 01.2012
Associate Professor
Tokyo University of Agriculture and Technology
04.2006 - 03.2011
Research Investigator
University of Michigan
04.1999 - 03.2006
Postdoctoral Fellow
Okayama University
10.1998 - 03.1999
Ph.D. - Engineering (Biological Sciences)
Okayama University
04.1995 - 09.1998
Research Assistant
Tokyo University of Agriculture
04.1992 - 03.1995
M.S. - Agricultural Chemistry (Nutritional Science)
Tokyo University of Agriculture
04.1990 - 03.1992
B.S. - Agricultural Chemistry (Nutritional Science)
Tokyo University of Agriculture
04.1986 - 03.1990
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