Dr. Yasumasa Ishida, M.D., Ph.D., Independent Associate Professor, Laboratory of Functional Genomics and Medicine, Division of Biological Sciences, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan

This is a summary of the curriculum vitae (CV) of Dr. Yasumasa Ishida, M.D., Ph.D., Independent Associate Professor, Laboratory of Functional Genomics and Medicine, Division of Biological Sciences, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan.

Dr. Ishida is known for his key contributions to the discovery and early research on programmed death-1 (PD-1), a critical immune checkpoint protein involved in regulating immune responses. When working for Professor Tasuku Honjo‘s lab at Kyoto University in the early 1990s, he was the first to discover the gene for PD-1 when looking for molecules contributing to T cell death in the thymus. Later, Professor Honjo’s group would demonstrate that PD-1 more generally acts as a negative regulator of immune responses, and that in a subgroup of cancer patients blocking PD-1 functions by antibody treatment strengthens their protective immune responses against their tumors. Professor Honjo would get the Nobel Prize for this work in 2018, together with Professor James Allison who made similar findings for another immune checkpoint molecule called CTLA-4,  Among the key publications selected by the Nobel Prize Committee for explaining the awarding of the Nobel Prize was Dr. Ishida’s paper (https://www.nobelprize.org/prizes/medicine/2018/press-release/):

The Key publications listed in the Nobel Prize Committee Press release as underlying the 2018 Nobel Prize in Physiology or Medicine by Professor Tasuku Honjo and Professor James P. Allison.

Dr. Ishida was born in Nagoya and was classmates with Professor Motoshi Suzuki of Fujita Health University, both in High School and later at Medical School of Nagoya University. At Medical School they also studied together with Professor Yoshiki Hirooka, now also working at Fujita Health University, and they have all been good friends ever since.

Dr. Ishida had a passion for research, and after getting his medical degree, he did his Ph.D. studies in the group of Professor Honjo at Kyoto University. As explained above, this culminated in his discovery of PD-1. However, even before that he already got publication in top journals like Nature (Nishi, Ishida, and Honjo, 1988) and Journal of Experimental Medicine (Ishida et al. 1989). Those studies were about the cytokine interleukin 2 (IL-2) and its specific receptor chain IL-2Rα (aka “CD25”). Although not known at the time, like PD-1, IL-2 and IL-2Rα are also very critical for the immune-inhibitory part of the immune system, and—at least in hindsight—Dr. Ishida’s early studies already provide hints toward this realization.

After his Ph.D., Dr. Ishida would remain in the group of Professor Honjo, where he was Assistant Professor from 1991-1996. The last three years of that period, however, he worked at Harvard University for Professor Philip Leder (1934-2020), who is a famous geneticist and won big prizes like the Lasker award in 1987. Here, Dr. Ishida developed a GFP-labelled retroviral “gene trapping” system for helping to find new gene functions, which was published in Nucleic Acids Research (Ishida and Leder 1999).
After coming back to Japan, Dr. Ishida first worked short periods as a Head at the National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, in the group of Dr. Kiyotoshi Kaneko, and as an Associate Professor at the Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, in the group of Professor Shimon Sakaguchi. In his work with Professor Sakaguchi, Dr. Ishida would meet an “old friend” in the form of IL-2Rα, now as a recognized marker of regulatory T cells (T cells that help to suppress immune reactions) (Shimizu et al., Nature immunology, 2002).
From 2001, Dr. Ishida then got his own group at the institute where he still works today, as an Independent Associate Professor in the Laboratory of Functional Genomics and Medicine, Division of Biological Sciences, Graduate School of Science and Technology, Nara Institute of Science and Technology, Nara, Japan. Here, he has kept working on topics in genetics and immunology, including in relation to cancer therapy, and with the further elucidation of PD-1 function as one of his major focuses.
In 2014, for his work on PD-1, Dr. Ishida received the JCA-CHAAO Award which is presented by the Japanese Cancer Association and the Chinese Anti-Cancer Association to individuals or groups that have made significant contributions to cancer research.
To end this Science Portrait of Dr. Ishida, it probably is nice to list some quotes from interviews with Professor Honjo:
Interviewer: ” When the PD-1 protein was discovered in 1992,were you already seeking to develop a drug for cancer treatment?
Professor Honjo: “No, I wasn’t. PD-1 was originally discovered by Dr. Yasumasa Ishida (currently an associate professor at the Nara Institute of Science and Technology), who was a graduate student at that time. He was searching for a molecule that could induce T-cell death, which had been a major challenge for the immune system.
In a 2021 interview, also looking back at the early days of PD-1 research:
Professor Honjo: “I was struck by the enthusiasm of Yasumasa Ishida who came to our graduate school after clinical training in Nagoya“.
It is a great pleasure and honor that Dr. Ishida will speak to Fujita University about his journey in PD-1 research!

Curriculum Vitae (CV)

EDUCATION & TRAINING

1980-1982

Premedical Course, Nagoya University School of Medicine

1982-1986

Medical Course, Nagoya University School of Medicine

1986:  M.D.

1986-1987

Resident of Internal Medicine, Aichi Cancer Center Hospital, Nagoya, Japan

1987-1991

Graduate School, Medical Chemistry, Kyoto University

(in the group of Professor Tasuki Honjo, who won the Nobel Prize in 2018)

1991: Ph.D.

 

PROFESSIONAL EXPERIENCE

1990-1991

Fellow of Japan Society for Promotion of Science, Department of Medical Chemistry, Kyoto University Faculty of Medicine

(in the group of Professor Tasuku Honjo)

1991-1996

Assistant Professor, Department of Medical Chemistry, Kyoto University Faculty of Medicine

(group of Professor Tasuku Honjo)

(1993-1996: Absentee Position)

1993-1999

Postdoctoral Research Fellow, Department of Genetics, Harvard Medical School, Boston, USA

(in the group of Professor Philip Leder)

1994-1998

Postdoctoral Research Associate, Howard Hughes Medical Institute

1999-2000

Head, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan

(in the group of Dr. Kiyotoshi Kaneko)

2000-2001

Associate Professor, Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University

(in the group of Dr. Shimon Sakaguchi)

2001-present

Independent Associate Professor, Laboratory of Functional Genomics and Medicine, Division of Biological Sciences, Graduate School of Science and Technology, Nara Institute of Science and Technology (Nara, Japan)

 

LIST of SELECTED PUBLICATIONS

Nishi, M., Ishida, Y., and Honjo, T. Expression of functional interleukin-2 receptors in human light chain/Tac transgenic mice. Nature 331, 267-269 (1988).

Ishida, Y., Nishi, M., Taguchi, O., Inaba, K., Hattori, M., Minato, N., Kawaichi, M., and Honjo, T.Expansion of natural killer cells but not T cells in human interleukin 2/interleukin 2 receptor (Tac) transgenic mice. J. Exp. Med. 170, 1103-1115 (1989).

Ishida, Y., Agata, Y., Shibahara, K., and Honjo, T.Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 11, 3887-3895 (1992).

Ishida, Y. and Leder, P. RET: a poly A-trap retrovirus vector for reversible disruption and expression monitoring of genes in living cells. Nucleic Acids Res. 27, e35 (1999).

Goodwin, N. C., Ishida, Y., Hartford, S., Wnek, C., Bergstrom, R. A., Leder, P., and Schimenti, J. C.DelBank: a mouse ES-cell resource for generating deletions. Nat. Genet. 28, 310-311 (2001).

Matsuda, E., Shigeoka, T., Iida, R., Yamanaka, S., Kawaichi, M., and Ishida, Y. Expression profiling with arrays of randomly disrupted genes in mouse embryonic stem cells leads to in vivo functional analysis. Proc. Natl. Acad. Sci. USA 101, 4170-4174 (2004).

Shigeoka, T., Kawaichi, M., and Ishida, Y. Suppression of nonsense-mediated mRNA decay permits unbiased gene trapping in mouse embryonic stem cells. Nucleic Acids Res. 33, e20 (2005).

Mayasari, N. I., Mukougawa, K., Shigeoka, T., Kawakami, K., Kawaichi, M., and Ishida, Y.Mixture of differentially tagged Tol2 transposons accelerates conditional disruption of a broad spectrum of genes in mouse embryonic stem cells. Nucleic Acids Res. 40, e97 (2012).

Shigeoka, T., Kato, S., Kawaichi, M., and Ishida, Y. Evidence that the Upf1-related molecular motor scans the 3′-UTR to ensure mRNA integrity. Nucleic Acids Res. 40, 6887-6897 (2012).

Yamanishi, A., Matsuba, A., Kondo, R., Akamatsu, R., Tanaka, S., Tokunaga, M., Horie, K., Kokubu, C., Ishida, Y.*, and Takeda, J.* (*corresponding authors) Collection of homozygous mutant mouse embryonic stem cells arising from autodiploidization during haploid gene trap mutagenesis. Nucleic Acids Res. 46, e63 (2018).

Ishida, Y.PD-1: its discovery, involvement in cancer immunotherapy, and beyond. Cells 9, 1376 (2020).

Nagaretnam, I., Yoneshige, A., Takeuchi, F., Ozaki, A., Tamura, M., Shigeoka, T., Ito, A., and Ishida, Y. (submitted & under revision). Granulomatous inflammatory responses are elicited in the liver of PD-1 knockout mice by de novo genome mutagenesis.

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