Metabolome Analysis

I am currently based not at the Shonan Fujisawa Campus (SFC), but at a place called the Tsuruoka Town Campus of Keio (TTCK) in Tsuruoka City, Yamagata Prefecture. Within TTCK is the Keio University Institute for Advanced Biosciences (IAB) , which conducts experiments and research using cutting-edge biotechnology. I am currently conducting research on cancer metabolism at this institute.

I am working on research into "the metabolism involved in cancer malignancy," with a particular focus on the epithelial-mesenchymal transition, or EMT.

EMT is a phenomenon in which cells in areas called "epithelia," such as the skin and organs, change into another form called "mesenchymal cells." "Epithelial cells" are nearly spherical, have strong bonds with each other, and are stable. In contrast, "mesenchymal cells" are flat and elongated, have weak bonds with each other, and are in an unstable state. It is known that when "epithelial cells" change into these "mesenchymal cells," their speed of movement and the distance they can travel increase.

While this phenomenon plays an important role in processes like fetal development and wound healing, in cancer cells, it is known to lead to cancer malignancy, such as metastasis to other organs and the acquisition of resistance to anticancer drugs. My research aims to comprehensively analyze what kind of metabolism occurs during this EMT in cancer cells, and I hope it will lead to the elucidation of the mechanisms of cancer malignancy and the development of treatments.

First, various individual factors that cause EMT have already been reported. One example is the protein "transforming growth factor," which I am also analyzing in my experiments, as well as environmental changes such as when oxygen fails to reach the inside of a tumor, creating a hypoxic state. There is also prior research suggesting that a gene related to a specific metabolism changes due to EMT, acting as a key factor.

Thus, it is thought that the mechanism of EMT development is not caused by a single factor, but involves many more enzymes and metabolites. However, no studies have yet been reported that comprehensively investigate them.

I want to uncover this complete picture, and I am advancing my research using a technique called "metabolome analysis," which this Institute for Advanced Biosciences focuses on.

"Metabolome analysis" is a technique for comprehensively analyzing where and how many metabolites—such as proteins, sugars, and amino acids—exist. Because it uses a highly precise mass spectrometer, it can measure a greater variety and number of substances with more accurate concentrations compared to conventional methods. By accurately measuring the functions of diverse metabolites and genes and analyzing how they are related, it is expected to lead to the elucidation of phenomena that were difficult to understand with conventional methods.

In my research, I use this analysis technique to verify the relationship between changes in cancer cell metabolism and genes.

The analysis begins by creating a place to grow cells, called a culture medium, in a container like a petri dish, and then culturing and multiplying the target cancer cells within it. After that, the multiplied cells are divided into those that will undergo EMT and those that will not, and the types and amounts of metabolites contained in each cell are measured with analytical equipment. The process involves analyzing the measurement data obtained in this way to clarify the differences and functions of the metabolites.

Data measurement takes about one to one and a half months, but the subsequent analysis is conducted from various angles, so it takes quite a long time.

The equipment used for analysis, called a mass spectrometer, is often limited to just one unit in a typical research institute, but at this TTCK, there are dozens of them. Since it is expensive equipment to begin with, it's often not in a state where students can easily use it.

At TTCK, there is an environment where even students can easily engage in this "metabolome analysis." Not only are the facilities extensive, but there is also a system for receiving guidance on how to use them, and I feel that they provide generous support for student research.

Furthermore, the Institute for Advanced Biosciences has many researchers who are active at the forefront, such as Professor Tomoyoshi Soga, who developed the mass spectrometer. Being able to conduct research near such individuals is a great learning experience and very stimulating.

I advanced to the Graduate School of Media and Governance from the Faculty of Environment and Information Studies, also at SFC. When I was in high school, I had the opportunity to hear a lecture by Professor Masaru Tomita, a professor at Keio University and also the Director of this Institute for Advanced Biosciences. I became very interested in cutting-edge biology and decided I wanted to go to SFC. There were many other universities with faculties related to biology and medicine, but as I listened to various stories, I was very attracted to the welcoming atmosphere for SFC students and the environment where I could focus on research.

Then, after entering the Faculty of Environment and Information Studies, I arrived at my current research from the perspective of "Can I use metabolome analysis to study the elucidation of disease mechanisms?" which I was originally interested in.

A major appeal of the Graduate School of Media and Governance is its curriculum that allows you to learn along with your research theme, and the system that makes it easy to go to Tsuruoka for research when you want to.

From my fourth year of undergraduate studies, my research at TTCK became my main focus. I completely moved my base to Tsuruoka and have been taking classes, doing practical training, and conducting experiments here. In Professor Tomita's lecture that inspired me to go to SFC, I also heard about "the state-of-the-art research institute in Tsuruoka City," and I had always hoped to one day conduct research in such an environment, so I was very happy to actually be able to do so.

I continued my research on cancer metabolism for four years starting from my undergraduate days, and it was so interesting that there were many things I thought, "I want to do this," and "I want to do that." It felt like a waste for the research to end in four years, so I decided to advance to the master's program and work hard on research for another two years. Therefore, I had no hesitation in advancing to the master's program.

I have now finished my first year of the master's program and have just entered my second, but I feel that I have even more things I want to know and do than I did as an undergraduate. The more research I do, the more results I get and the more things I don't understand, so I have a strong desire to research more and learn more.

The best thing about coming to Tsuruoka is that I can concentrate on my research.

I currently live in a dormitory for affiliates of the Institute for Advanced Biosciences staying at TTCK. It's located close to the institute, making it a very easy environment to commute.

I can go to the university as soon as I feel like it, and go home as soon as my research is done. I feel that my personal life and my research are very integrated. The time I spend on research and the time I spend on my normal life are very close within a single day, and the feeling that research has become a part of my life is very comfortable for me.

I also feel that the human connections at TTCK are very close. Since many people live in the same place, there are many opportunities to share meals, and I think the members who participate become very good friends.

My supervising professors are always ready to consult with me not only during the weekly scheduled meetings but also whenever I get experimental results or have something I don't understand. As for the students, most of us live in the same dormitory or conduct experiments and work in the same building, so we spend a lot of time together both inside and outside the lab. We plan costume Halloween parties using the wellness room on campus, and we celebrate various milestones together with events like farewell and welcome parties, birthday parties, and cherry blossom viewing.

I believe the Graduate School of Media and Governance is an environment where, if you decide what you want to do and take action, there are many people who will support you.

Although I had the desire to do cancer research, I entered the program without even knowing how to conduct an experiment. From there, I believe I was able to advance my research by proactively seeking opinions from the professors and senior students at the institute. My seniors taught me how to use the laboratory and experimental methods from scratch, and I gradually became able to do more. With proposals and support from the professors, I feel I've made it this far.

At first, it may feel difficult to take the initiative, but precisely because it's a place where many people will help you, I really want you to go and talk to them. I think it's a graduate school where you can have various experiences depending on your own motivation and effort, so I recommend "just trying it."

Through "metabolome analysis" so far, I have been able to find several candidate genes that become key when metabolism changes due to EMT. Currently, I am trying to verify whether these genes are actually key, as well as what relationship they have with cancer cell migration and the acquisition of resistance to anticancer drugs.

Also, in the future, I hope to contribute to the development of treatments and therapeutic drugs that can suppress cancer malignancy. It may be difficult to create a drug directly from my research, but I would be very happy if this research serves as a catalyst, drawing attention to the metabolism of cancer cells or leading to more advanced research, ultimately resulting in the development of new drugs. The type of cancer cells and the patient's condition differ from person to person, and their environment and feelings also vary. An increase in the types of therapeutic drugs leads to more choices for patients. They can choose various drugs according to their own situation. I hope things will develop in that direction.

First, I want to summarize the research I am currently doing and present it externally by the time I complete my master's program. Beyond that, I hope to leverage the biotechnology research and experimental techniques I have learned at this Institute for Advanced Biosciences to contribute, even in a small way, to the advancement of medicine and life sciences in the future.

The Graduate School of Media and Governance is, I believe, an environment that supports what you want to do.

As I've advanced my research, I've often felt supported by various people and systems—the curriculum, professors, senior students, and my peers. So, the idea of a "supportive environment" feels just right for me.

Keio University Institute for Advanced Biosciences

Advanced Biosciences Research Group

Keywords: Advanced Biosciences, Systems Biology, Bioinformatics, Biotechnology, Life Science Informatics, Genetic Information Processing, Metabolomics, Analytical Chemistry, etc.

Research Content: The Tsuruoka Town Campus of Keio (TTCK), the base of operations, was established in Tsuruoka City, Yamagata Prefecture, in April 2001 in collaboration with Yamagata Prefecture and the municipalities of the Shonai region.

The Institute for Advanced Biosciences, also founded at TTCK in 2001, uses cutting-edge biotechnology to comprehensively analyze biological data such as genomes, metagenomes, transcriptomes, proteomes, and metabolomes, and advances research to understand this massive amount of data through computer analysis, modeling, and simulation. It has garnered worldwide attention as a pioneer in a new life science called "Integrated Systems Biology," based on this big data. In recent years, these technologies have not only created breakthroughs in bioscience but have also been applied to fields such as medicine, health, the environment, and agricultural, forestry, and fishery products and foods, leading to the birth of numerous venture companies.

At TTCK, undergraduate and graduate students from the Shonan Fujisawa Campus (SFC) stay and follow a curriculum focused on learning life sciences. A year-long "Advanced Biosciences Program" is offered for students of the Graduate School of Media and Governance.

At SFC, computer-based practical courses such as "Biosimulation" and "Genome Analysis Programming" are offered in a state-of-the-art network environment. At TTCK, experimental practical courses such as "Genome Engineering Practice" and "Proteome Analysis Practice" are available, using the latest CE/MS, DNA sequencers, and bioreactors.