Lab Spotlight: Yamazaki Lab

Each month, Simply Blood spotlights a lab contributing to the fields of hematology, immunology, stem cell research, cell and gene therapies, and more. Get to know groups doing cutting edge research from around the world! This month, we are featuring the Yamazaki Lab which is based out of The Institute of Medical Science, The University of Tokyo in Japan (https://www.cbms.k.u-tokyo.ac.jp/en/labs/yamazaki/).

You have quite a unique career path, aren’t you? So when and how did you start considering becoming a PI?
I did not think I would be able to become a PI in the past. (*Prof. When he started working in this field, Yamazaki was a technical staff, not even a bachelor's student.) At that time, simply performing experiments was fun, so I did not prioritize obtaining academic degrees. Later, however, I started feeling more fun writing a paper by myself, with which I could connect myself and discuss science with other national and international researchers worldwide. My desire to spread my idea and developed technologies to the world through my own research funding led me to become a PI as a result.

Having said that, you are not just one of the PIs but have already become a world-leading scientist. So it must be based on your unique ideas; where do those unusual ideas originate?
Basically, I have a twisted mind; I do not easily tap into current trends and follow facts that everyone blindly believes. So from where do my ideas come? Of course, I have learned stem cell biology, molecular biology, and medical sciences as a minimum requirement, but additionally, I briefly studied other fields of sciences (physics, astronomy, etc.) as well to apply some ideas to our projects. It might have made me slightly different from other researchers, and I believe it is the right thing.

What is the current central research theme of your lab?
The first one is how to expand HSC ex vivo efficiently. The protocol recently published in Nature (ref.1) is still at the basic research level; hence, we aim to increase the efficiency sufficient for clinical applications, particularly overcoming individual differences. As the next one, since hematopoietic stem cells are now understood as a heterogenous population, we are trying to uncover the identity of each HSC, not simply using typical transcriptomic analyses but with kinetics analysis, imaging approaches, and mathematical modeling. In addition, we are interested in genome editing and gene therapy.

You have worked on many types of research topics in the hematology field. Which works were turning points for your research theme and/or career?
The most important paper for me is the one studying roles of lipid raft formation in HSC published in the EMBO journal, in which we could visualize signal transductions in HSCs (ref.2). It was the first time I could complete my own idea as a scientific paper, so quite memorable and feeling as an origin of my current research. In such a sense, not only the papers published in top journals such as Cell (ref.3) and Science (ref.4), but also the one in Stem Cell Reports (ref.5) is also unforgettable since all of those papers made me confident to be a researcher, not just a technical staff.

Which of your own published papers would you choose as your favorite one?
In terms of successful ex vivo HSC expansion, instead of the murine HSC expansion using polyvinyl alcohol published in Nature (ref.6), I would select the Stem Cell Reports paper (ref.4). Because, in that paper, we discovered the cause of the functional diversity of albumin between different lots, to which no others were paying attention. Therefore, I felt, “Take that!”.

What is the tip for organizing the lab well? What do you think is important for that?
Besides providing an excellent research environment, including materials and equipment, selecting projects that both PI and students/researchers agree on and are interested in is imperative. The lab members might lose motivation if the PI enforces a project without sufficient discussion. Therefore, in my lab, each member sometimes works on two projects; the agreed project (mainly based on PI’s interest) and projects considered by the lab member. Of course, it depends on the financial situation, but I think it is an essential experience to fail on projects initiated by themselves.

Do you have any advice for junior researchers willing to become PI?
Sometimes, I see junior researchers who published a paper in top journals from a big lab and become independent PI; however, they have trouble managing the lab and finally quit science. Regarding lab management, it would be important to learn from philosophy. For example, we can study how to manage one team (or community, society) from China's Sanguozhi (Three Kingdom Saga). Historically, many people have been considering methods to operate organizations nicely for more than 2000 years – there are many hints from such literature. In my feeling, studying one of the main themes in philosophy - what are humans? - would help the way to tackle issues happening in the lab.

Could you name a couple of concrete people you learned from?
Personally, thoughts of Marcus Aurelius Antoninus make me calm when I need to have patience in human relationships. In the case of Sanguozhi, I liked Han Fei’s idea.

When you feel stressed, how would you release it? I remember you liked driving when you were working as a technical staff.
Yes, I still like driving! Every day I commute from my house in Yokohama to my office in Tsukuba, approximately 100 km in one way, by driving, which is an excellent way to release stress. In addition, I like playing games, especially Nintendo Switch is my favorite.

However, when can you read books if commuting takes so long?
I am using Amazon Audio Book to read the book during driving. It’s very convenient, I use it to check typos in my new grant applications as well.

In the long run, what would you like to achieve?
As the basic science, I want to make discoveries that can revert stereotypical ideas regarding stem cells. As a clinical application, I dream of bringing our achievements to actual therapies.

How ISEH benefits you and your research?
I am an ISEH member and attend most of the annual meetings. This is the only scientific community focusing on “deep” basic hematology. I have attended many national and international hematology-related meetings, but ISEH feels like a “home” to me. It is definitely a benefit for the members to communicate with so many world-leading researchers through this excellent society.

Prof. Satoshi Yamazaki

Division of Cell Regulation,  

Center of Experimental Medicine and Systems Biology, 

The Institute of Medical Science, The University of Tokyo.

References

1. Sakurai M, Ishitsuka K, Ito R, et al. Chemically defined cytokine-free expansion of human haematopoietic stem cells. Nature. 2023 Mar;615(7950):127-133.
2. Yamazaki S, Iwama A, Takayanagi S, et al. Cytokine signals modulated via lipid rafts mimic niche signals and induce hibernation in hematopoietic stem cells. EMBO J. 2006 Aug 9;25(15):3515-23.
3. Yamazaki S, Ema H, Karlsson G, et al. Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell. 2011 Nov 23;147(5):1146-58.
4. Taya Y, Ota Y, Wilkinson AC, et al. Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation. Science. 2016 Dec 2;354(6316):1152-1155.
5. Ieyasu A, Ishida R, Kimura T, et al. An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors. Stem Cell Reports. 2017 Mar 14;8(3):500-508.
6. Wilkinson AC, Ishida R, Kikuchi M, et al. Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature. 2019 Jul;571(7763):117-121.

Blog post contributed by Kenichi Miharada, PhD, ISEH Publications Committee

Please note that the statements made by Simply Blood authors are their own views and not necessarily the views of ISEH. ISEH disclaims any or all liability arising from any author's statements or materials.