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Toshio Kitamura: a pioneer of retrovirus-mediated expression cloning

Posted By Connections Editor, Wednesday, March 6, 2013
Updated: Tuesday, February 26, 2013

Toshio Kitamura, M.D., Ph.D.
Division of Cellular Therapy and Division of Stem Cell Signaling
The Institute of Medical Science
The University of Tokyo

Dr. Kitamura’s interest in hematology and stem cell research began early in his career. "When I was working as a physician in the university hospital, I was very interested in observing the blood smears of patients with hematological malignancies,” Dr. Kitamura explains. "I wanted to understand the reasons behind the morphological changes of blood cells.” This curiosity motivated Dr. Kitamura to join the department of hematology-oncology at the hospital in 1983 as a clinical hematologist.

After six years of clinical and research training at the University of Tokyo and the Cancer Center Institute, Dr. Kitamura moved to the US to work at DNAX Research Institute of Molecular and Cellular Biology as a postdoctoral fellow. It was here that he met a key mentor, his supervisor Dr. Atsushi Miyajima. "He allowed me to do the experiment based on my hypothesis,” says Dr. Kitamura of his supervisor. "He also gave me an important suggestion for establishing an expression cloning system based on retrovirus-mediated gene transfer, because he knew how interested I was in retrovirology. Through his work as a postdoctoral fellow at DNAX, Dr. Kitamura presented the first evidence for the common subunit shared between multiple cytokine receptors.

Four years later Dr. Kitamura started his own laboratory at DNAX Research Institute. He wanted to present his research findings at ISEH and become a member of the society. His lab now has thirteen graduate students, two postdoctoral fellows, three assistant professors, and a technician. Dr. Kitamura emphasizes the importance of understanding and valuing each student and fellow’s unique strengths. "I always try to encourage students and postdoctoral fellows to continue to think about science. I also make recommendations on how the students and fellows should proceed in their careers based on their individual aptitudes.” He often recommends that his students and fellows go abroad for their research. Dr. Kitamura also offers these wise words for new investigators entering the field: "Thinking is the most important and valuable part of being a scientist. If you love to think and speculate, you will have a better chance of becoming a great scientist.” He also explains that because researchers can now isolate hemopoietic cells as well as patients’ leukemic cells with high purities, research in hematology often leads other fields.

Dr. Kitamura’s current research focuses on genetic and epigenetic control of leukemogenesis, in particular the roles of mutations in epigenetic regulators including EZH2, TET2, and ASXL1. His research has made some exciting discoveries. "Mutations in EZH2, TET2 or ASXL1 alone induce MDS-like symptoms in mouse models. We identified one of the underlying molecular mechanisms of ASXL1 mutation-induced MDS,” Dr. Kitamura explains. In addition, Dr. Kitamura contributes to the field by offering a cytokine-dependent TF-1 cell line which he established from one of his patient in 1987, as well as a retrovirus vector pMX and a packaging cell line PLAT-E. These tools are now widely used by the scientific community.

Dr. Kitamura has also borne witness to the rapidly evolving nature of hematological research. He notes that comprehensive analyses are increasingly common, including whole genome sequencing; whole genome methylome; expression profiles, and ChIP-seq. Computers are now necessary to analyze the huge amount of data derived from these comprehensive studies. Additionally, he identifies the greatest challenge now facing the hematology and stem cells field: discovering a method to eliminate leukemic stem cells. "I do not know how it can be managed,” Dr. Kitamura states. "It’s possible that this goal will be reached with a chance factor.”

Dr. Kitamura comments that while he has been able to secure funding for his research thus far, there is an increasing tendency toward funding translational research rather than basic science, particularly since the development of iPS cells in Japan.

Dr. Kitamura has been a member of ISEH for over 20 years. In addition to holding the post of the Associate Editor for Experimental Hematology, he has also been a member of the Board of Directors, as well as a part of a number of ISEH committees. He enjoys being part of a close community with good basic and clinical science. He believes that ISEH offers many opportunities to young researchers. He is always happy to attend the ISEH Annual Scientific Meeting to see his many friends within the ISEH community. His favorite ISEH memory is of driving the Monte Carlo F1 racecourse at an Annual Scientific Meeting.

Dr. Kitamura enjoys listening to Pink Floyd music, reading Haruki Murakami novels, and playing golf. He also plays the drums in a rock band called Negative Selection, which consists of five researchers in hematology and immunology.

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