Professor Masaru Ishii, Department of Immunology and Cell Biology, Graduate School of Medicine / Graduate School of Frontier Biosciences
“Splitting the “AtoM” in search of a treatment for rheumatoid arthritis”
Inside live bones, “osteoclasts” and “osteoblasts” are constantly generated. The former breaks down bones while the latter synthesize them. Under well-balanced bone destruction and formation processes, bones continually destroy and form themselves.
In his latest study published in Nature Immunology [1], Dr. Ishii and his research team developed a unique technology to collect and analyze cells from arthritic joints, successfully identifying a new type of bone-destroying osteoclast that contributes to rheumatoid arthritis (RA), called Arthritis-associated osteoclastogenic Macrophages, or “AtoMs.” They found that the arthritis-inducing osteoclasts have properties and origins that are distinct from normal osteoclasts involved in bone metabolism. By specifically inhibiting the differentiation and functions of arthritis-inducing osteoclasts without affecting normal osteoclasts, their discovery will aid in the establishment of breakthrough therapy and the development of anti-RA drugs.
Utilizing global experience to start a revolution
Dr. Ishii became interested in live bone tissues as he treated patients suffering from RA while working as a clinical immunologist. “RA may be cured if the mechanism of how solid bones are dissolved is discovered,” he thought. “To achieve this, it is important to observe live cells moving inside bones in a living body.”
He then devoted himself to the bioimaging of bone, which may have roots in his short stay as a medical visiting student in Germany, where he observed living cells under a microscope in a laboratory. Later, when he was engaged in his research at NIH in the United States as a Human Frontier Science Fellow, he was invited to IFReC to lead a project that spans the fields of immunology and imaging technology. In 2012, he succeeded in the world’s first dynamic observation of immune cells in bones [2].
Breaking the mold to create new fields with a global mindset
Dr. Ishii’s has unique bioimaging equipment installed in his lab, which gathers a lot of interest and requests for studying and joint research from students and researchers from all around the world. He is also actively engaged in building a global community of co-workers on the common platform of “research” and enjoys holding discussions with them, as they enrich his life as a researcher. Above all, discussions with researchers with different backgrounds and cultures bring about new ideas for research. Research advances at blistering speeds, with new changes occurring in rapid succession. Japan is a world leader in the field of immunology, and as one of the forerunners in this field, Dr. Ishii has addressed new challenges in the fusion between immunity and imaging as well as in informatics as he continues to push forward in his research endeavors.
“I want to keep opening up new fields of research with a global mindset. More specifically, I want to bring about a medical revolution by allowing healthcare professionals to see what takes place in a living body.”
[1] T. Hasegawa et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nature Immunology 20. 1631-1643 (2019). DOI: https://doi.org/10.1038/s41590-019-0526-7.
[2] J. Kikuta et al. Dynamic visualization of RANKL and Th71- mediated osteoclast function. The Journal of Clinical Investigation. 2013; 123(2):886-873.DOI: https://doi.org/10.1172/JCI65054 .
Text: Saori Obayashi/Edit: Christopher Bubb