Honorary Membership Award
A career of groundbreaking discovery, built on a philosophy of curiosity
Dr. Nobutaka Hattori shares the journey and mindsets that have driven him to become one of the preeminent leaders in the field.
I wanted to work in a profession that would benefit people, so I entered the Juntendo University School of Medicine and graduated in 1985. I was torn between hematology, cardiology, psychiatry, and neurology as my major department. Still, I decided to major in neurology because the first professor of neurology, Dr. Hirotaro Narabayashi, is a famous neurologist, and there are many excellent staff members in the medical department.
Initially, I studied neurophysiology and assisted in H-reflex research on Parkinson's disease. 1989 saw the arrival of the second professor, Prof. Yoshikuni Mizuno, and the research focus of our department shifted from neurophysiology to neurobiochemistry. Under the guidance of Prof. Mizuno, I entered the graduate school of Juntendo University in 1990. The same year, I went to Nagoya City to study molecular biology at the Second Department of Biomedical Chemistry, Nagoya University Faculty of Medicine.
The structural analysis of the NDUFV2 gene, one of the subunits of mitochondrial electron transport complex I, was my first basic research and was the research theme I was given. We screened the lambda phage library, a classical method, to reveal the genetic structure. We were able to publish a paper in the BBRC in 1995, although another laboratory team eventually surpassed us. My wife and I were newlyweds then, and she shared our hardships with me in Nagoya, a city far from Tokyo. It was a difficult time for both of us, but we have good memories of it now.
I had to return to Tokyo in the middle of my work and joined the laboratory of Prof. Nobuyoshi Shimizu at Keio University to complete it. It was there that I came to know about the Keio BAC library. Under the leadership of Prof. Mizuno, we found that the locus for young-onset Parkinson's disease (AR-JP) was localized to the long arm of chromosome six, and that the microsatellite marker D6S305 was absent in one family line. Based on the information of this family, we isolated and identified the parkin gene in one year using the Keio BAC library. This was when I realized that all is well and that ends well.
Since entering graduate school, I have been working hard on mitochondrial research and hereditary Parkinson's disease. In the functional analysis of Parkin, I asked Prof. Keiji Tanaka of the Tokyo Metropolitan Institute of Medicine Science to collaborate with us to identify it as a ubiquitin ligase. This was the first time a proteolytic system was proven to be involved in neurodegenerative diseases. This discovery is regarded as a breakthrough.
In 2016, I succeeded Prof. Yoshikuni Mizuno as a professor and chairman in the Department of Neurology at Juntendo University, where I have continued my research on metabolomics and blood biomarkers with a focus on hereditary Parkinson's disease, starting with the parkin (Nature, 1998), followed by CHCHD2 (Lancet Neurology, 2015), and PSAP (Brain, 2020). CHCHD2 and PSAP products are associated with mitochondrial and lysosomal functions, respectively. In addition, we are interested in the relationship between biomarkers and PD. We have developed real-time quaking-induced conversion combined with immunoprecipitation, a method that enables the detection of α-synuclein seeds from the serum of patients with synucleinopathies. This method can lay the foundation for the biological diagnosis of synucleinopathies (Nature Medicine, 2023).
I have published more than 1,000 scientific papers. This is the result of the achievements of our staff members. As a clinical department, our basic policy is to obtain all ideas from patients. In our academic work, we have always been aware of Louis Pasteur's maxim, “Chance favors only the prepared mind.” Research always leads to discoveries by always wondering why and how. When I encounter a complex case, I always question what differs from the typical case, and this curious mind leads to discoveries.
What I must remember is "human connections.” I have been blessed with many friends both in Japan and abroad. I have met and developed friendships with all my friends from abroad at the MDS International Congress. My most important belief is that “hard work is on my side.” No matter what the situation is, there is always a chance. This award encourages me to continue to focus on my clinical, research, and educational activities, all for the benefit of Parkinson's disease patients.