Fluorescence light micrograph of human pancreatic cancer cells obtained in the laboratory. An AMED-funded study has found that the fibroblasts (green) surrounding pancreatic tumors (red) that express a protein called Meflin help keep the cancer in check (nuclei in blue).© 2020 Atsushi Enomoto
In terms of government funding agencies for medical research, the Japan Agency for Medical Research and Development (AMED) is a mere baby, being just five years old. But already in its brief existence the agency has funded about 660 billion yen (approximately 6 billion US dollars) of research, which has been generating impressive results in a diverse range of fields.
Japan is facing some special challenges, mainly due to its super-ageing population. Already more than 28% of Japan’s population is over 65 and that figure is predicted to rise to 35% by 2040. There is thus an urgent need to address age-related health problems such as cancer, heart disease, dementia, diabetes and depression. Fortunately, emerging technologies including artificial intelligence (AI), big data, and regenerative medicine are promising for tackling these challenges.
Realizing the power of AI and stem cells
The exciting potential of AI is just beginning to be unleashed in medical research and applications. In some instances, AI can even outperform human experts, but an ongoing problem is that its process is opaque to humans. Now, an AMED-funded project led by Yoichiro Yamamoto of RIKEN has lifted the lid on the black box of AI. His team used a deep-learning system to predict the probability that prostate cancer will reoccur within one year based on pathology images from patients and other data. The AI results were more accurate than those of human pathologists. But importantly, the deep-learning system also generated images that highlighted the regions that had the highest AI-assigned weightings, thus enabling human researchers to glean new knowledge. “AI says these images are very important for predicting cancer recurrence, but you won’t find them in pathology books produced by humans,” says Yamamoto. “This is new knowledge.”
Another exciting technique that promises to revolutionize healthcare is regenerative medicine. An area of Japanese research strength, many AMED projects are focusing on this emerging field. For example, a team led by Kohji Nishida from Osaka University used reprogrammed stem cells to repair the cornea of a Japanese woman — a world first. Also, a team led by Emi Nishimura of Tokyo Medical and Dental University has shown that competition between skin stem cells helps keep skin youthful in young people, but later in life the same process leads to ageing of skin. Uncovering this process will help researchers identify targets to counteract skin ageing.
Shedding light on Parkinson’s disease and cancer
Increasing life expectancies are leading to greater occurrences of neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases. This has led to some researchers to call dementia the greatest health challenge of our time. By using state-of-the-art imaging techniques on autopsied brain tissue, AMED-funded researchers have observed the distinctive atomic structure of abnormal protein aggregates in the brains of people with Parkinson’s disease for the first time. “This could be important evidence to support the prion hypothesis of Parkinson’s disease,” says Hideki Mochizuki, a neurologist at Osaka University, who led the study, referring to the idea that pathogenic protein aggregates can propagate through the brain.
An AMED-funded project has discovered how to identify cells expressing a protein that curtails pancreatic cancer growth in mice, which could provide a new way to fight the cancer.© Science Photo Library - STEVE GSCHMEISSNER/Getty
Another formidable challenge is cancer. Researchers supported by AMED’s Japan Cancer Research Project have found a way to identify cells expressing a protein that curtails the growth of pancreatic cancer in mice. A team led by Atsushi Enomoto from the Nagoya University Graduate School of Medicine discovered that a protein called Meflin is expressed on the surface of cancer-restraining fibroblasts. This could provide doctors with a new way to fight pancreatic cancer. “A therapy that specifically controls Meflin expression could be valuable,” says Enomoto. And potentially this discovery could have wider relevance. “We need to look at other cancers in the future,” Enomoto adds.
The benefits of being a reviewer
Before a project can be funded it needs to be assessed by experts in the field. AMED is keen to increase input from international reviewers to ensure greater diversity of opinions. “We need to catalyze medical R&D,” says Makoto Suematsu, president of AMED. “That’s why I believe international collaboration and the English-language peer review system are so important.”This opportunity has mutual benefits — researchers in other countries gain an insight into the latest research being conducted in Japan, while AMED gains a global perspective on potential research projects, leading to better informed funding decisions. In the long term, it is hoped that these benefits will lead to even greater collaboration between Japanese and international researchers and thus advance medical research globally.
Reviewers receive recognition and an honorarium for their work and an improved awareness of what makes for a strong grant proposal — always helpful when it comes to applying their own grants. But the main reward is a knowledge that having contributed to the advance of medical research and a glimpse it affords into a better future.
To find out more about becoming a reviewer of AMED grant proposals, please see the following website: join-reviewer.amed.go.jp