What made you initiate your current research?

As a matter of fact, I came up with the idea for this research when I was a graduate student. At that time, a classmate of mine, Student A, who was also a graduate student, and I were in the same laboratory. Although he was really clear-headed, he was uncooperative, often causing conflicts with other laboratory members. One day, as always, after he broke the laboratory rules (he didn’t clean up beheaded rats), I went to the bathroom shaking with anger. In the bathroom, I was trying to think of a way to deal with him. It was after murmuring, "He is a 'cancer.' How can we get rid of him?" that I came up with this idea. "What happens with real cancer?" In our society, when an unruly punk appears, the police handle it. At the same time, with a person who is only slightly bad, such as Student A, those around that person attempt to exclude or correct that person. Similarly, highly malignant tumor cells are handled by special cells referred to as immune cells, while the surrounding normal cells may handle slightly bad mutant (precursor) cells. This is an interesting idea! Upon searching through a variety of literature, I could not find any reports regarding the mutual interaction between normal epidermal cells and mutant cells, so from then on I became excited to study this hypothesis.

Figure 1. The appearance of Src mutant cells being ejected from the normal cell layer
Src cells stained with a fluorescent dye (CMTPX) were mix cultured with non-stained normal epidermal cells, after which they were observed with a time-lapse microscope over time.
Time is the elapsed time inducing Src activation. The red arrows indicate the Src mutant cells.

Unfortunately, I was not given an opportunity to study this theme as a graduate student or in my post-doctoral research; however, after leaving the laboratory, I finally had an opportunity to initiate this research in my own laboratory in London. One day in 2005, together with a post-doctoral researcher, Catherine, upon examination of the outcome of mixing normal cells and oncogeneic protein Src mutant cells using a time-lapse microscope, we observed the Src mutant cells being ejected from the normal cell layers (Figure 1). The normal cells eliminated the Src mutant cells from their society. I still cannot forget the excitement of watching that video at that time.

 

What kind of equipment do you use and what kind of experiments do you conduct?

In our laboratory, we study cancers mainly through cell biology and biochemical methods. Incubators and incubation rooms to culture normal epidermal cells and cancer cells are required. In addition, we examine the dynamics of these cells using various types of microscopes (e.g., confocal microscopes: used for observing the microstructure of cell interiors and cell membranes; time-lapse microscopes: used for observing cell dynamics with videos). Moreover, we make full use of various techniques including electrophoresis, immunoprecipitation, and gene amplification, in order to analyze intracellular genes and proteins.

 

What is your next goal?

In the past, using the cultured cells of mammals, we reported, for the first time in the world, that mutant cells surrounded by normal cells end up dyeing or being excluded from the body. As such, it has been revealed that normal cells have the ability to destroy various types of mutant cells. At the same time, the molecular mechanisms of how normal cells recognize mutant cells and eliminate them have not been elucidated at all (Figure 2). Currently, in my laboratory, we are focusing all our energy on exploring the significant molecules related to these phenomena. If molecules functioning at the boundary between normal cells and mutant cells are determined, those molecules will become the target of medical agents. In advancing this research, my goal is to lead the development of entirely novel cancer therapeutics that "make surrounding normal cells attack cancer cells." I approach my daily research with a strong motivation to save patients suffering from cancer.

The whole point of science is that it is "international." There is little meaning if a "discovery" is not the first in the world. Only world-first discoveries gain a high reputation. There is no better feeling than that which comes with the superiority of looking at the data and thinking "I may be the first to have found this." Every day will be the Olympics for you. Through providing such enjoyable experiences in science to young students, I wish to train world-class, next-generational researchers.

Figure 2. Phenomena occurring at the boundary of normal cells and mutant cells