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Welcome to the Masuda Laboratory
Exercise Physiology, Mitochondrial Biology and AI for Science

The Masuda Laboratory at Kanazawa University investigates the molecular mechanisms underlying skeletal muscle adaptation to exercise. Our research began with physiological studies of oxygen delivery, intracellular oxygen transport, and energy metabolism in contracting skeletal muscle. Building on this foundation, we have expanded our work into mitochondrial biology, protein trafficking, molecular imaging, multi-omics, and AI-assisted scientific discovery.

Our central question is:
How does exercise remodel skeletal muscle mitochondria and improve cellular function?
To address this question, we integrate exercise physiology, biochemistry, molecular and cellular biology, animal models, proteomics, bioinformatics, structural analysis and artificial intelligence.
 
Current Research Projects
1. Myoglobin Trafficking and Mitochondrial Function

Myoglobin is expressed mainly in skeletal and cardiac muscle. In addition to its established role in oxygen storage and transport, our findings suggest that myoglobin is present within mitochondria and interacts with components of the mitochondrial respiratory chain.
We are investigating:
- how myoglobin is imported into mitochondria;
- whether conventional or non-canonical mitochondrial import pathways are involved; how exercise training alters mitochondrial myoglobin;
- how myoglobin interacts with mitochondrial respiratory complexes; and
- how mitochondrial myoglobin affects respiration, ATP production, metabolism, and cellular homeostasis.

2. Discovery of Non-canonical Mitochondrial Proteins

Most mitochondrial proteins are encoded by nuclear genes, synthesized in the cytosol, and subsequently imported into mitochondria. However, proteins that are not conventionally annotated as mitochondrial may transiently or conditionally localize to mitochondria and regulate mitochondrial function.
We use mitochondrial purification, proteomics, biochemical assays, and bioinformatics to:
- compare mitochondrial proteomes among different skeletal muscle types;
- identify proteins altered by exercise training, aging, or metabolic stress; determine the submitochondrial localization of candidate proteins;
- predict targeting signals and import pathways;
- analyze protein–protein interactions; and
- experimentally determine how candidate proteins modify mitochondrial function.

3. Exercise Training, Detraining, and Muscle Memory

Previous exercise experience can influence the response of skeletal muscle to later retraining. This phenomenon is often referred to as muscle memory. We investigate whether such memory involves not only muscle hypertrophy but also mitochondrial quantity, respiratory capacity, protein composition, and gene regulation.
Our approaches include:
- endurance and resistance exercise models;
- training, detraining, and retraining protocols;
- skeletal muscle histology; mitochondrial respiration;
- RNA sequencing; proteomics;
- analysis of myonuclei; and
- epigenetic analyses, including histone modifications.
This work may provide a molecular basis for individual differences in exercise responsiveness and for the development of more effective retraining strategies.

4. Live-cell Molecular Imaging

Mitochondrial and metabolic responses vary across intracellular space and time. We are therefore developing live-cell imaging approaches, including fluorescence lifetime imaging microscopy (FLIM), to quantify molecular events in individual muscle cells.
Our current targets include:
- intracellular Ca²⁺; ATP; lactate and other metabolic intermediates;
- intracellular temperature; and
- spatial and temporal changes in mitochondrial function.
These imaging approaches are combined with overexpression, knockdown, knockout, and other experimental models of candidate mitochondrial regulatory proteins.

5. AI-driven Omics and Structural Analysis

Our laboratory is participating in the Japanese AI for Science initiative through the research project: “AI-driven Omics and Structural Analysis for the Prediction and Validation of Skeletal Muscle Mitochondrial Trafficking and Interaction Factors.”
This project integrates:
- mitochondrial proteomics;
- transcriptomic data;
- protein sequences and domains;
- subcellular localization information;
- protein–protein interaction networks;
- three-dimensional protein structures;
- public biological databases; and
- scientific literature.

We aim to construct an AI-assisted research pipeline that:
- identifies proteins detected in skeletal muscle mitochondrial fractions;
- extracts proteins not conventionally annotated as mitochondrial;
- integrates omics, localization, sequence, interaction, and
- structural information;
- prioritizes candidate mitochondrial trafficking and regulatory factors;
- generates experimentally testable hypotheses; and
- validates selected candidates through wet-laboratory experiments.
The experimental results will be returned to the analytical pipeline to improve candidate selection. Through this iterative Dry–Wet research cycle, we seek to use AI not merely to automate analysis, but to generate new biological hypotheses and accelerate scientific discovery.
 
Experimental and Analytical Approaches
Graduate students may have opportunities to learn and use:
- animal exercise models;
- skeletal muscle sampling and histological analysis;
- cell culture and muscle-cell differentiation;
- mitochondrial isolation and purification;
- mitochondrial respiration assays;
- Western blotting and immunochemical analyses;
- quantitative PCR;
- proteomics and transcriptomics;
- fluorescence and lifetime imaging;
- protein localization and import assays;
- bioinformatics; protein structure and interaction analysis;
- R and Python; and
- AI-assisted data integration and hypothesis generation.

The specific methods used by each student depend on the research question and project.

Research Vision
Our long-term goal is to understand how exercise and other physiological stimuli remodel skeletal muscle mitochondria and thereby improve cellular and whole-body function.
We seek to translate basic discoveries into knowledge relevant to:
- healthy aging;
- prevention of metabolic disease;
- skeletal muscle dysfunction;
- individual variation in exercise responsiveness;
- evidence-based exercise prescription;
- athletic conditioning; and
- precision exercise medicine.
Our laboratory is entering a new stage in which exercise physiology, mitochondrial biology, molecular imaging, multi-omics, and artificial intelligence converge. We aim to contribute to the development of AI-driven exercise biology, while maintaining experimental validation as the foundation of reliable scientific discovery.
 
Opportunities for Graduate Students and Researchers
We welcome motivated students and researchers interested in interdisciplinary studies involving exercise physiology, skeletal muscle biology, mitochondrial function, molecular biology, bioinformatics, or AI for Science. Applicants to the master’s or doctoral programs are encouraged to contact us before submitting a formal application.
Please provide:
- a curriculum vitae;
- a summary of your previous research;
- your academic background and technical experience;
- your proposed research interests;
- your reason for wishing to join our laboratory; and
- information about your intended scholarship or funding source.

Applications to our graduate programs are welcome. If you have any questions about applying to the master’s or doctoral program, postdoctoral opportunities, or research collaboration, please feel free to contact us by e-mail. We would be pleased to hear from prospective students and researchers whose academic backgrounds and research interests align with our laboratory.
International applicants considering the Japanese Government (MEXT) Scholarship should contact us well in advance of the application deadline. Acceptance into the laboratory and selection for a scholarship are separate processes and cannot be guaranteed.

Supervisor
Kazumi MASUDA, Ph.D., Professor
< Brief C.V. >
PhD in Exercise Science from Univ. of Tsukuba, Japan (1999.Mar),
Research Associate at Center for Tsukuba Advanced Research Alliance, Univ. of Tsukuba, Japan (~2001.Dec),
Associate Professor in Exercise Physiology at Faculty of Education, Kanazawa Univ., Japan (~2009.Mar),
Professor in Exercise Physiology at Faculty of Human Sciences, Kanazawa Univ., Japan (2009.Apr~)
Laboratory Personnel & Graduate Groups
Dr. Tsubasa Shibaguchi, PhD, Institute of Liberal Arts and Science, Kanazawa Univ., Japan
Dr. Muhammad Isman Sandira, PhD, Faculty of Education, Kanazawa Univ., Japan
Dr. Aki Kawamura, PhD, JSPS PD, Faculty of Education, Kanazawa Univ., Japan
Mrs. Rie Yamada, Technical Assistant, Faculty of Human Sci, Kanazawa Univ., Japan
Others... (some undergraduate students)
Collaborators
Dr. Hisashi Takakura, PhD, Doshisya Univ., Japan
Dr. Yasuro Furuichi, PhD, Tokyo Metropolitan Univ., Japan
Dr. Tatsuya Yamada, PhD, Univ. of Nebraska–Lincoln, NE, USA
Dr. Ronald DR Hamidie, PhD, MD, Faculty of Medicine, Univ. Pendidikan Indonesia
Prof. Thomas Jue, PhD, Univ. of California Davis, USA
Dr. Ulrike Kreutzer, Univ. of California Davis, USA
Dr. Rie Ishizawa, National Institute of Fitness and Sports in Kanoya, Japan
Dr. Yoshiteru Hanai, Nagoya Institute of Technology, Japan
Dr. Yutaka Kano, Univ. of Electro-Communications, Japan
Dr. Takeshi Hashimoto, Ritsumeikan Univ., Japan
Dr. Nobumasa Iwanaka, Kyoto Seika Univ., Japan
Prof. Koji Ishida, Nagoya Univ., Japan
Prof. Hiroshi Akima, Nagoya Univ., Japan
Prof. Keisyo Katayama, Nagoya Univ., Japan
Prof. Satoshi Iwase, Aichi Medical Univ., Japan
Prof. Aki Hirayama, Tsukuba Univ. of Technology, Japan
Dr. Kai Tanabe, Univ. of Tsukuba, Japan
Prof. Thomas Reilly, Liverpool John Moores Univ., UK (passed on June 11, 2009)
Recent Publications
1. Hamidie DRR, Shibaguchi T, Yamada T, Koma R, Ishizawa R, Saito Y, Hosoi T and Masuda K: Curcumin induces mitochondrial biogenesis by increasing cyclic AMP levels via phosphodiesterase 4A inhibition in skeletal muscle. Br J Nutr 126: 1642-1650, 2021.
2. Koma R, Shibaguchi T, Pérez-López C, Oka T, Jue T, Takakura H and Masuda KCA: Localization of myoglobin in mitochondria: implication in regulation of mitochondrial respiration in rat skeletal muscle. Physiol Rep 9:e14769, 2021.
3. Yamada T, Takakura H, Jue T, Hashimoto T, Ishizawa R, Furuichi Y, Kato Y, Iwanaka N and Masuda K: Myoglobin and the Regulation of Mitochondrial Respiratory Chain Complex IV. Journal of Physiology 594: 483-495, 2016.
4. Hamidie DRR, Yamada T, Ishizawa R, Saito Y and Masuda K: Curcumin treatment enhances the effect of exercise on mitochondrial biogenesis in skeletal muscle by increasing cAMP levels. Metabolism 64: 1334-1347, 2015.
5. Yamada T, Furuichi Y, Takakura H, Hashimoto T, Hanai Y, Jue T and Masuda K: Interaction between myoglobin and mitochondria in rat skeletal muscle. J Appl Physiol 114: 490-497, 2013.
6. See more information on the Publication page.

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