2006 - Tadatsugu Taniguchi

Graduate School of Medicine and Faculty of Medicine
University of Tokyo, Japan

Motivation:
The 2006 Pezcoller Foundation-AACR International Award for Cancer Research is given to Tadatsugu Taniguchi, PhD for his groundbreaking discoveries that have had a major impact on cancer research and molecular immunology, which include isolation and characterization of the first cytokine genes (interferon-β; and interleukin-2), discovery of the IRF family of transcription factors, and elucidation of their functions.
Dr. Taniguchi began his career with the major discovery and characterization of the human IFN-β gene, the first interferon and cytokine gene to be identified. In collaboration with Charles Weissmann, he then elucidated the primary structure of type I interferon proteins and demonstrated that IFN-α and IFN-β genes constitute a gene family. This was the first cytokine gene family to be identified. He went on the identify and characterize the human IL-2 gene and isolate the gene encoding the IL-2 receptor β chain. His work demonstrated for the first time that the IL-β chain transmits signals by recruiting non-receptor tyrosine kinases that contribute to the regulation of T cell responses. By generating recombinant IL-2, he made it possible to study the molecular basis of lymphocyte proliferation. His work has led to the first demonstration that IL-2 can promote the growth of B cells and natural killer (NK) cells, in addition to T cells. Availability of recombinant IFN and IL-2 has made possible their use for clinical applications in cancer, hepatitis, and multiple sclerosis, and for studies of molecular signaling mechanisms.
Dr. Taniguchi’s research on cytokine gene expression and signaling led to the discovery of a family of transcription factors, the interferon regulatory factors (IRFs). He demonstrated the important and broad functions of IRF-1 and IRF-2 in the regulation of interferon responses and other immune functions. He also elucidated the general regulatory mechanisms of IFN-α/β gene induction, involving two other members of the IRF family, IRF-3 and IRF-7. Identification of the IRF family broadly impacts cancer research. Dr. Taniguchi’s work determined that IRF-1 regulates cell cycle arrest in cooperation with the tumor suppressor protein p53, that it is involved in the regulation of apoptosis, and that the loss of IRF-1 cooperates with deficiency in p53 function to promote tumorigenesis. This led his group to discover that interferons regulate p53 expression, which established important links between IRFs, interferon signaling, immunity and oncogenesis, the knowledge of which can be exploited for cancer therapy. Finally, Dr. Taniguchi discovered that p53 is activated in cells by virus infection, and he provided evidence that this mechanism plays a role in the elimination of virus-infected cells by apoptosis.
The importance of the IRF family members has been further corroborated with the recent demonstration of their key roles in Toll-like receptor (TLR) signaling in innate and adaptive immune responses. Dr. Taniguchi showed that both IRF-5 and IRF-7 interact with MyD88, the adaptor critical for TLR signaling. He showed that MyD88-dependent activation of IRF-5 is essential for the TLR-mediated induction of pro-inflammatory cytokines (TNF-α, IL-6, IL-12), whereas the activation of IRF-7 is essential for the potent induction of IFN-α/β by TLR9. He also showed that the MyD88-IRF-7 pathway is critical for generating a CD8+ cytotoxic T cell response, knowledge of which is essential for understanding anti-tumor immunity.
Dr. Taniguchi received a BSci in biology at the Tokyo University of Education and a PhD in molecular biology from the University of Zurich and is currently Professor and Chair of the Department of Immunology at the University of Tokyo. He has published over 200 papers and is the recipient of many major honors including the Hammer Prize, Behring-Kitasato Prize, and the Robert Koch Prize. He is a Foreign Associate Member in the U.S. National Academy of Sciences. Dr. Taniguchi has served as Co-Chairperson of the AACR International Affairs Committee and is Associate Editor of Cancer Research.

2006 - TADATSUGU TANIGUCHI
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