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CREST Research Supervisor Dr. Toshio Suda talks about iPS cell research and what will come next (2) -All 4 episodes-

Dr. Toshio Suda

In CREST, we concentrate our efforts on " fundamental research towards application"
Understanding epigenetics and germ cells is a key to innovation after Prof. Yamanaka

Interviewer :
By the way, you are the Research Supervisor of the research area "Fundamental Technologies for Medicine Concerning the Generation and Regulation of Induced Pluripotent Stem (iPS) Cells" of CREST, JST. How did you set the goals in the research area?

Dr. Toshio Suda

Suda :
For clinical applications of iPS cells, there is another MEXT research project, "The Project for Realization of Regenerative Medicine", led by Dr.Shin-ichi Kohsaka (Program director) and program officers. In my CREST, we concentrate our efforts on basic studies before clinical applications, for example, for understanding the mechanisms of cell reprogramming, and developing technologies for reprogramming. The project also includes studies relatively close to clinical applications, for example on disease models.
We also attach much importance to basic studies on epigenetics and germ cells.

Interviewer :
I did not know the word "epigenetics" until recently.

Suda :
Many scientists have come to take up epigenetics as an important subject since only several years. Epigenetics is a young discipline and research has just started.
We already knew that clone animals or monozygotic twins that were identical in their genomic DNA sequences might show different expressions of a genetic predisposition. Recently we have noted that factors other than the DNA sequences are responsible for changes in gene expressions (epigenetic changes) : chromatin structure, microRNA (small molecule RNA), methylation and acetylation of DNA, and chemical modification of histones.

For example, there is an inherited disease called "thalassemia". In thalassemia patients, normal adult hemoglobin is not produced.
n adults, fetal hemoglobin is usually not produced as transcription of the responsible gene is inhibited by DNA methylation. Some scientists had an idea that it would be possible that in thalassemia patients, they give a chemical agent to induce DNA demethylation and supply fetal hemoglobin as a substitute for adult hemoglobin. However, a technique for "targeted methylation" is not yet available, and it might be difficult to develop such a technique.

Interviewer :
You attach much importance to germ cell research in your project, aren't you?

Suda :
In my research area, there are researchers who are working on germ cells.
I am sure that epigenetics will be the most important area of research after iPS cells.
Our studies are to understand the characteristics of germ cells that control epigenetic mechanisms, and not to manipulate these mechanisms.

Germ cells are committed and differentiated in early stages of development. When they are primordial germ cells, DNA demethylation occurs and all epigenetic changes are reprogrammed, and, DNA methylation recurs when they become a sperm or ovum.

Dr. Toshio Suda

Interviewer :
Why is the process so complicated?

Suda :
We do not know yet the mechanism. Some explain that it is to distinguish maternal genes and paternal genes, or memorize them in the cells.

Interviewer :
Reprogramming occurs again in a fertilized ovum.

Suda :
When we produce a clone animal (a frog or Dolly, for example), we transfer a nucleus into an ovum, and immediately after the transfer, the ovum reprogram all the genes of the nucleus introduced.
When we generate iPS cells, we reprogram differentiated cells by adding transcription factors. If we understand the mechanism of reprogramming in the nuclear transfer, it will give us an idea to develop a technique for generating iPS cells without using transcription factors.

Interviewer :
That is an interesting research. I am sure that there are many people involved.

Suda :
Unexpectedly, there are not so many people involved in this area of research. It seems that most people are interested in applications of iPS cells in regenerative medicine. Japan is leading this field, and I hope that this study will lead to an innovation "post Dr. Yamanaka".


Interviewed by Katsuaki Sato,Mio Watanabe(Japan Science Technology Agency)
Published on 16 March, 2010

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Dr. Toshio Suda

Professor for developmental biology courses, The Sakaguchi Laboratory, School of Medicine, Keio University, visiting professor at the Institute of Molecular Embryology and Genetics, Doctor of Medicine, physician, and, certified physician and educator of the Japanese Society of Hematology.

In 1974 : Graduated from School of Medicine, Yokohama City University
Since 1974 : Resident physician at the Department of Pediatrics, Kanagawa Children's Medical Center
Since 1978 : Assistant at the Department of Hematopoiesis, Institute of Hematology, Jichi Medical University
Since 1982 : Research associate at the Department of Internal Medicine, Medical University of South Carolina
Since 1984 : Instructor at the Department of Hematopoiesis, Institute of Hematology, Jichi Medical University
Since 1991 : Associate professor of hematology at the Department of Hematopoiesis, Institute of Hematology, Jichi Medical University
Since 1992 : Professor at the Division of Developmental Regulation, the Institute of Molecular Embryology and Genetics, School of Medicine, Kumamoto University
Since 2000 : Chief at the Institute of Molecular Embryology and Genetics, School of Medicine, Kumamoto University
Since 2000 : Professor at the Department of Hematopoiesis, the Division of Organogenesis, the Institute of Molecular Embryology and Genetics, School of Medicine, Kumamoto University
Since 2002 : The present post

From 2000 to 2004 : Project leader of "Characterization of Somatic Stem Cells and Tissue Reconstruction", Research for the Future Program, Japan Society for the Promotion of Science.
Since 2008 : Research Supervisor of "Fundamental Technologies for Medicine Concerning the Generation and Regulation of Induced Pluripotent Stem (iPS) Cells", CREST, JST, and committee member of The Japanese Society of Hematology.

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