InaRIS Fellow (2024-)

Ayuko Hoshino

Professor, Research Center for Advanced Science and Technology, The University of Tokyo *Profile is at the time of the award.

2024InaRISBiology & Life sciences

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Research topics: Exosomes, a new player to unravel disease biology

Summary: Exosomes, minute vesicles roughly the size of viruses, carry a diverse range of biomolecules originating from their parent cells. While previously regarded as a mechanism for processing cellular waste, recent years have unveiled the uptake of exosomes from originating cells by other cells, garnering attention as a novel intercellular communication tool. This study aims to explore how the interaction mechanism between cells mediated by exosomes, vesicles diffusing within the body, may connect tissues located remotely. This connection could potentially impact the development and progression of various diseases, thereby introducing novel physiological concepts.

Citation

Exosomes are granule particles, ranging from 30 to 150 nm in diameter, released by all types of cells. They are tiny capsules containing lipids and proteins from the cell membrane on their surface, and RNA, DNA, and other proteins inside. Because exosomes carry these components from the originating cells and are found in fluids such as blood, cerebrospinal fluid, and urine, they can be considered cellular metabolites. This has made them attractive as biomarkers for liquid biopsies, allowing for cancer detection and classification based on exosomal contents. However, recent research suggests that exosomes play a more active role than simply being cellular metabolites. They are increasingly recognized as a means of intercellular communication.

While at Cornell University, Dr. Ayuko Hoshino encountered the intriguing concept of the pre-metastatic niche. This theory proposes that tumors prepare their future homes—metastatic sites—before actual metastasis happens. In essence, the targeted organs are “conditioned” in advance. In the course of her work, she found that intravenous administration with exosomes derived from lung-metastasizing cancer cells, followed by an injection of bone-metastasizing cancer cells, significantly increased lung metastasis despite that these cancer cells were incapable of metastasizing to the lungs on their own. This study suggested that exosomes secreted by cancer cells determine where metastasis will occur.

Dr. Hoshino’s pioneering work not only demonstrated the groundbreaking concept that exosomes can act as messengers for cell-to-cell communication, but she is also boldly extending this concept to understand a diverse range of conditions beyond cancer metastasis, including neuropsychiatric disorders, the mother-fetal relationship, and aging. She has already found that brain disease-related exosomes can cross the blood-brain barrier. This opens up possibilities for studying autism spectrum disorder (ASD), schizophrenia, and Alzheimer’s disease. Dr. Hoshino’s research aims not only to develop diagnostic markers based on exosomal analysis but also to elucidate new pathology by studying the linkage between the brain and other organs in these diseases. As for the mother-fetal relationship, Dr. Hoshino’s team administered exosomes from mothers of children with ASD to pregnant mice and observed autism-like behaviors in the resulting pups. She will further investigate the potential influence of maternal exosomes on fetal development and vice versa. For example, the impact of fetal and placental exosomes on the mother, such as in gestational hypertension, will be explored. Regarding aging, her team has already collected over 200 healthy human plasma exosomes. An in-depth analysis of these exosomes may hold the key to unlocking their role in the aging process. Dr. Hoshino’s unique research will be conducted multidisciplinarily, with a convergence of clinicians, engineers, physical chemists, and machine learning experts. This convergence holds immense promise for the future development of innovative medical treatments based on the power of exosomes.

Dr. Hoshino studied applied chemistry at the Tokyo University of Science and then received her degree in advanced life sciences from the University of Tokyo. She is an up-and-coming researcher who became a professor at the University of Tokyo’s Research Center for Advanced Science and Technology in 2023 after researching exosomes at Weill Cornell Medicine for nine years and then working as an associate professor at the Tokyo Institute of Technology.

Although hormones are well-known for their role in long-distance communication between organs, the mystery of how the exosome system evolved and how it impacts specific targets remains a subject of endless fascination. We expect Dr. Hoshino to elucidate an extensive picture over the next 10 years as an InaRIS fellow.

Message from Fellow

As I approach my forties, I've been reflecting on ways to create an environment that fosters deep dedication to research. This ten-year fellowship offers a valuable chance to achieve this goal. In addition to investigating the potential roles of exosomes in both pathological and physiological contexts, I am committed to mentoring new researchers. Guiding them during this fellowship period will deepen our understanding of exosomes beyond the scope of this funding.