What is the current focus of your research, and what do you find most rewarding about your work?
Through the use of "reverse reduction-ism” based approaches, the Takebe Laboratory investigates:
• The development of complex human organoid models;
• The self-driven mechanisms of organogenesis;
• Developing technology prototyping towards drug discovery/transplant applications.
Through these efforts, with a major focus on foregut- and midgut-derived systems, our lab aims to contribute to human health by establishing new therapies especially for treating intractable pediatric disease.
What led you to become a scientist and to stem cell research?
I had always been interested in transplantation. In my later medical school years, after a career-changing experience in New York, I became interested in growing livers in a dish for future transplantation. While spending time as part of a surgical elective at Columbia University, one of the world’s largest liver transplant centers, I was forcibly struck by patients dying from liver failure owing to organ shortage crisis. Facing many such patients, my aspiration moved towards the establishment of an alternative approach to transplantation. After obtaining my MD degree, I accepted a research position at Yokohama City University in Japan and decided to initiate studies on the then emerging field of induced pluripotent stem (iPS) cells, with an approach to translate knowledge of organogenesis into organoid-genesis using stem cells.
What is the most exciting aspect of your work?
I am always intrigued by nature’s amazing ability to make precise organ systems. In the embryo, organ-forming cells rely on an elaborate communication system involving nearby cells to develop into three-dimensional organs. Such robust, reproducible and stereotypic capacity of organogenesis can be translated into experimental approaches to make miniature organs in a dish, so called organoids.
In 2011, I coaxed the formation of liver-cell precursors, or hepatoblasts, from pluripotent cells and mixed them with mesenchymal and endothelial cells, almost serendipitously, on NON-cell culture petri dishes (I had mistakenly grabbed the “wrong” plates, which were not suitable for monolayer cell culture), and found a surprising degree of self-organization into miniature 3D tissues. I still remember coming into lab and visualizing these mind-blowing spheroid formations, which my less-than-impressed lab-co-workers thought were merely “contamination”. My team has since built additional complexity into the liver system. We have integrated endothelial cells, macrophages, and most recently extra hepatic biliary systems into our ‘miniature livers’ (or organoids).
What guidance would you share in talking with trainees interested in pursuing your area of research?
Summarized below is my philosophy in pursuing research in science:
1. “Imagine, Small”: Think weird / crazy / small ideas, constantly share your thoughts with others, and don’t forget that the simplest experiment may be the most critical.
2. “Involve, Friends”: Define what you cannot do and find collaborators. Interact with people with different backgrounds and expertise.
3. “Inspire, People”: Amplify your small idea, visualize its potential, and inspire!
Creation from zero is always a risk and takes tremendous courage to commit and accept the outcome. This ability to make a conscious, risky, decision is unique to human beings, and we, as scientists, should exploit it.
Do you have any mentors or individuals who have inspired you in your stem cell work?
- Hiro Nakauchi: my mentor from early medical school days till now.
- The late Yoshiki Sasai’s review article published in Nature, which defined cytosystems dynamics, inspired me a lot in the design of my experiments.
- James Wells & Aaron Zorn: Amazingly collaborative and complementary laboratories that jointly mentor both me and my team in Cincinnati.
How do you spend your free time?
I spend most of my free time working on a life passion that is not related to stem cells. I am working on design-based approaches that promote the well-being and awareness of the general population through various daily touch points. As a proof-of-principle, I have voluntarily worked with artistic creators for over 8 years (since I was a med student), most of whom are in advertising. In 2018, I founded a state-of-the-art design center at my alma mater Yokohama City University Medical School: the YCU-Communication Design Center (YCU-CDC). Recruited faculty and staff include graphic designers, copy writers, web editors, and educators and we collaborate with local design firms and advertising agencies. In a recent project we used a "fashion-based" approach to fight obesity by visualizing body shape.
What is something your peers would be surprised to learn about you?
I multitask across many different disciplines, ranging from stem cells to design.
What do you most value about your membership with the ISSCR?
I appreciate the super-generous community, activities, and very friendly and instructive leadership, which is balanced by the highest-level of stem cell science. I also find that active strategies of inclusion, by age, gender, and international diversity and so on, is very helpful for interacting with diverse people, which I really enjoy.