JSPS Quarterly
No.53 2015 Autumn

Research and Life in Japan by a JSPS Fellow (35)

Dr. Jorge Luis Espinoza Calderon

JSPS Postdoctoral Fellow, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 2014-present
Visitor Research Fellow, Hematology Branch, National Institutes of Health, USA, 2012-2014
Research Fellow, Department of Cellular Transplantation Biology, Kanazawa University, 2010-2012
Emergency Medicine Attendant Physician, Department of Emergency Medicine, Baptist Hospital of Nicaragua, 2002-2005
Clinical Medicine Instructor, National University of Nicaragua, 2002-2005
M.D., National University of Nicaragua, 1997

Hailing from Nicaragua, Dr. Jorge Luis Espinoza Calderon has been conducting research with his host professor Dr. Shinji Nakao at Kanazawa University under a JSPS postdoctoral fellowship. We asked him about his research and life in Japan.

Please tell us about your background.

Before coming to Japan, I had been working as a medical doctor at a national university in Nicaragua. I was trained in emergency medicine there. At some point, I decided to switch to another field. I was motivated to study cancer, but in my country I didnít have an opportunity to do so. We didnít have a research culture because clinical treatment was given higher priority. Then, I found that the embassy of Japan in Nicaragua was offering a scholarship to go to Japan to take a doctoral course.
I completed my doctoral program under the mentorship of Dr. Nakao at Kanazawa University, thanks to a MEXT scholarship. Thereafter, I moved to the US to do a postdoctoral fellowship at NIH. During my tenure in the US, I continued my research collaboration with Dr. Nakao. Early last year, I met him at a symposium in the US and we talked about applying for a JSPS fellowship to conduct an advanced study using the iPS technology to understand the pathogenesis of aplastic anemia.

How is that research going under the JSPS fellowship?

At the Department of Cellular Transplantation Biology in Kanazawa University and in collaboration with researchers from Kyoto University, I am using iPS cells derived from patients with aplastic anemia to generate functional hematopoietic cells (blood cells) for the purpose of identifying potential mechanisms that cause this life threatening disease and to ultimately design novel treatments. This disease is characterized by a failure in the production of blood cells resulting from the destruction of the patientís blood stem cells (blood cells in the bone marrow that give rise to all other blood cells).
It is known that in aplastic anemia the blood stem cells are destroyed by the patientsí own immune cells as part of an abnormal immune response, which is triggered by still unknown mechanisms. Because of the low number of blood cells in the bone marrow of patients with aplastic anemia, it has been intrinsically difficult to study this disease systematically. Taking advantage of iPS cell technology, we are now able to generate a sufficient number of blood stem cells from patients with aplastic anemia. These cells will be excellent tools for understanding the cause of this disease and thus developing novel therapeutic approaches.
At the same time, in collaboration with other researchers in Japan, I am trying to identify new pharmacological agents (preferentially non-toxic drugs) with therapeutic potential for certain types of blood cancers that are refractory to currently available treatments and therefore have a poor prognosis.

Thatís a very interesting research subject. How did you become engaged in it?

When I was doing my doctoral and postdoctoral research, I was involved in several projects, one of them being the identification of mechanisms that make the immune cells of aplastic anemia patients destroy their own blood stem cells. The discovery in 2006 by Dr. Shinya Yamanaka of Kyoto University that adult cells can be genetically reprogrammed to a pluripotent stem cell state revolutionized the stem cell field, offering a new tool for scientists to study the ways diseases develop, opening the potential use of iPS cells in regenerating damaged tissues of the body. I was wondering whether iPS cell technology could be effectively applied to the study of aplastic anemia.

How did you get to know your Japanese host, Dr. Nakao?

I found him through an Internet search and learned about his clinical work at Kanazawa University. I was very impressed by the success that he and his staff achieved with a novel technique called ďmini-transplantĒ for the effective treatment of certain blood cancers. That mini-transplant is less toxic than a normal transplant. His research work on aplastic anemia is also highly recognized throughout the world. I wanted to do research related to clinical practice because of my background as a doctor, so I found that Dr. Nakaoís laboratory would be a good place for me.

What are your research achievements so far working with Dr. Nakano?

Over the past few months, we have optimized a method for generating blood cells from iPS cells in the laboratory. We have succeeded in generating blood stem cells from iPS cells derived from patients with aplastic anemia, and we have characterized those cells in terms of certain factors that may determine their susceptibility to destruction mediated by the patientís immune cells.
In the other studies, I have found a highly promising agent that may be effective in the treatment of acute myeloid leukemia. In our assays, this agent has shown extraordinary efficacy in eliminating cancer cells while sparing normal cells, a feature that accounts for its low toxic profile.

You have research experience in both the US and Japan. What is your impression of Japanís research environment?

I think there are clear cultural differences between the countries. In general, it seems that Japanese scientists tend to work under a hierarchical model of research, in which tradition plays a crucial role. Conversely in the US, scientists tend to work in a rotating model. Although there are differences in the ways research is conducted, I believe that Japanese scholars are also conducting excellent research. Regarding more specific differences, I think that one big difference is the budget. In the US, research grants from NIH are several times more than those in most institutions in Japan. Another important difference is that in the US there is more collaborative research between academic institutions and industry.

What is your impression of your host institution?

Kanazawa University is a medium-sized national university with a respectable research infrastructure. I am very impressed with how much the research facilities in the university have improved over the last few years with the acquisition of modern equipment and cuttingedge apparatuses to perform advanced research. Dr. Nakaoís laboratory provides a free environment in which to pursue research with talented students and faculty staffs. That creates a friendly and harmonious atmosphere for the overseas researchers.
I also remember that when I was in the doctoral course, I received very good service from the universityís international office. They organized trips within Japan for the international students and were always very nice. They also offered Japanese learning classes at the universityís main campus, which I used to attend.

Your Japanese pronunciation is very good. Did you begin learning Japanese before you came to Japan?

I feel the same when I talk with Japanese people who have learned Spanish, which is my native language. I think the phonetic sounds in the two languages are quite similar.
I studied hiragana (a set of about 50 Japanese characters) in Nicaragua, and thought that Japanese was easy to learn. However, when I came to Japan I realized that kanji (a set of over 2,000 characters derived from Chinese) is most important in oneís everyday life. Learning kanji, however, is difficult for me.

What do you think of life in Japan - its culture and customs?

Japan is completely different from the country where I grew up; however, Japan has transformed me in many aspects. Japanís orderliness and civility are virtues that amazed me from the first time I had contact with this country. Another stunning characteristic of Japan is the perfect mixture of modernity and tradition, while obviously safety and efficiency are distinctive of this country as well. My country was devastated by civil wars from 1970 toward 1990 and during that time the nation was also shocked by various natural disasters, including an earthquake that completely destroyed the capital city in 1972. Unfortunately, our responses to those adversities were not the best. I wish we could have had a little of the perseverance, civility and stoicism and all those virtues that have helped Japan to recover from massive natural disasters and the destruction caused by World War II.

When do you feel Japanese civility in your daily life?

I can feel it almost every day. For example, if you come to Japan, even when passing through immigration at an airport, you will really feel welcome. That is not only at airports, but everywhere you go Japanese people are very kind. Even if you donít speak Japanese, they will try to help you.

What do you plan to do after your fellowship ends?

I wish to continue my research in the fields of andrology/urology. I will need to discuss and consult with my professor, Dr. Takenaka, about my future path. If I have a chance to do so, I would like to continue my research in Japan before moving back to Greece.

What do you plan to do after your fellowship ends?

I will go back to my home country. Hopefully the faculty position in the university hospital will still be open to me. If so, I will have a chance to not only work as a healthcare provider, but also to continue my scientific research. I want to share the knowledge and experiences I have gained in Japan with colleagues and students in Nicaragua. My ultimate goal is to achieve discoveries that can be effectively translated into therapies, so I will be focused on studies that have clinical potential.

Pl ease g ive some adv ice for young researchers who may be thinking about doing research in Japan?

I think the JSPS program offers a great opportunity not only to conduct advanced research for your professional development but also to enjoy life in Japan. I am really grateful to have been awarded this fellowship. Japan may be quite different in many ways, particularly for Westerners. However, I believe that enjoying Japanís unique culture and customs is the first step to turning differences into a successful experience. In addition, it is crucial to have a good relationship with your host researcher and colleagues. I would like to end by paraphrasing Facundo Cabral, who was a Latin-American philosopher. He said something that may seem obvious and quite simple but it is filled with a lot of wisdom, ďBe aware of the present because life is here and right now, take care of the present, because in it, you will live the rest of your life.Ē We have the tendency to pay too much attention to the future and do not pay enough attention to the present, but in fact the present is the only time we can give to whatís important while living in this world.

After our interview with Dr. Luis Espinoza, we met his host Dr. Nakao and laboratory colleagues, and were very impressed with the glowing and closeknit collegial relationship they share. Dr. Luis Espinozaís conversation with us demonstrated just how productive such close collaboration can be as they work to apply iPS cells to elucidating the pathology of diseases whose causal mechanisms have been difficult to understand. He and his colleagues are already achieving significant results that can lead to the development of much needed and hoped for treatments and cures. We are greatly encouraged that even after returning to Nicaragua, Dr. Luis Espinoza will continue working with his Japanese colleagues in an effort to ďachieve discoveries that can be effectively translated into therapies.Ē

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JSPS Quarterly No.53 2015