A Conversation with Distinguished Researcher Satoshi Okada
On February 1, 2013, Hiroshima University established two new programs: the “Distinguished Professors” (DP) program and the “Distinguished Researchers” (DR) program. Individuals who are part of these programs are recognized as senior and junior faculty members respectively, who are engaged in extraordinarily distinguished research activities.
What is your name and specialist field?
My name is Satoshi Okada and my field of study is primary immunodeficiency. We study patients from a genetic aspect. Patients are compromised hosts, so they show susceptibility to bacteria and viruses. Patients with primary immunodeficiency have a genetic defect. Genetic defect immune-related genes can result in a person with lack of immune cells because of developmental problems.
What new research projects do you have coming up?
Very recently we are focused on the coronavirus, COVID-19. We would like to sequence the genome of patients with severe symptoms associated with COVID-19, especially in children. We know that many children don’t show symptoms. Our hypothesis is children who develop severe symptoms associated with COVID-19 will have some genetic defect. This gene should be very important for host-defense against COVID-19.
We are now tackling this project with many collaborators, including France, Australia, Tokyo, and Rockefeller University in the U.S. We don’t know why young people don’t show strong symptoms. This is a big question. If we find the cause, the important part and possibility is that we develop some treatment. To develop treatment, we need a target.
How did you get into this field of work?
When I became a physician, I did general pediatrics looking for infectious diseases and developmental delays, such as epilepsy. I did general pediatrics for five years. After that job, I went back to university to do my PhD. I started focusing on primary immunodeficiency, and simultaneously, I took care of the patients with endocrinological problems in outpatient care. In our department, PhD students needed to select a field, so I selected pediatrics as an endocrinologist. It was a completely different field from my research field. But it is very good because some of the patients with primary immunodeficiency have some endocrinological defects. There is a link.
What is the best thing about your research work?
My best output from my research was the identification a patient with a mutation of STAT1, a molecule, which mediates cytokine signaling. We identified a patient with a gain-of-function mutation, so the mutation increased activity of STAT1, and such a patient developed a chronic mucocutaneous candidiasis—a rare genetic condition in childhood that impacts skin, nails, and mucosal sites. We identified this molecule in 2011 and the paper was in the Journal of Experimental Medicine.
For publication, the best thing was the identification of RORγt, the master transcription factor of Th17 cells, which helps in the process of eliminating mycobacteria that have entered the body. The findings were published in Science. There have been ten patients identified with this gene.
But for clinical impact, identification of STAT1 gain-of-function has been the best part for me. Up until now, nearly 400 or 500 patients with this disorder are reported worldwide.
What are you most proud of from your work?
The best thing is the thing I am most proud of—the work on STAT1 gain-of-function.
What is the challenge of doing this research?
Identifying responsible genes is very challenging. It’s like fishing.
To find such a gene defect effectively, collaboration is very important. Collaboration is really important because our research is on very rare diseases that affect only a small number of patients in the whole world, so we need to collaborate with many laboratories.
What is the future outlook of this field?
In the future we need to focus on treatment. Gene therapy will be a future prospect for therapy. Right now, we look for the genetic defects and analyze related pathways. Gene editing and gene therapy are the future prospective, but it will take time.
What is your daily work schedule like?
I became a professor in March 2020. There are now many things to do outside of the research. A few years ago, I spent most time writing grant application, mentoring students, and doing research. Now, I can help decide the best direction for research. This is a good part.
Do you still have the same enthusiasm for your work?
Yes. For example, we now want to focus on COVID-19. It is an exciting opportunity. I am very curious, and I am always looking for good targets for research. People should be curious, especially scientists.
What is the best thing about working at Hiroshima University?
I think the people in Hiroshima are very kind and members of our department are really nice people. I am happy to work with such people. I want to say thanks to the PhD students who are working with me. Thanks to them, we have research results based on their hard work. Recently, I don’t have a time to do benchwork. So, I just think about research and writing grants and papers. However, thanks to kind and gentle people, I can continue my research.
What would you like to improve on?
This year I became a professor and it was a step up. Now my goal is to lead a successful department of pediatrics where people are happy and productive.
What are your feelings about collaboration?
For me, collaboration is really important. I want to have many collaborators and trusting collaborators. In the majority of the work, collaboration is a win-win. In 2010, I went to Rockefeller University for my postdoc. My boss from my postdoc is a giant in this field. I still work with him. He invited me to a worldwide collaboration for COVID-19.
How would you describe your work with students?
Research needs interpretation. I discuss results with students and tell them my opinion. Sometimes the discussion changes the direction of the research, so this is very important for the PhD student. We share ideas to breakthrough problems. Sometimes there is a wall to jump. My goal is to be a good teacher to help them with those problems.
When you are not in the office what do you like to do?
For one year, I have been jogging. I’m just a beginner. I ran five kilometers, slowly, in 45 minutes, one or two times a week. My good collaborator likes hiking and he sometimes invites me to a lab retreat. The last time was 2017 and we climbed a mountain. I needed to prepare. At that time, my preparation was walking. I walked to work every day from my home— about 15 to 20 minutes. That was my exercise for four years. We planned a retreat for this year, but it was postponed. We had planned to climb the mountain, so I prepared one year by jogging. That was my motivation!
What will you be doing five years from now?
Previously, we focused on the genome, or DNA, to find genetic defects. But the molecule diagnostic rate is one in three—30 percent. To increase this rate, we are now trying Omics analysis, which means we analyze RNA and protein. Such a large rate of study will increase diagnostic rate.