Professor Junichi Takagi is the winner of the 2023 FAOBMB Entrepreneurship Award
Professor Junichi Takagi
Institute for Protein Research, Osaka University, Japan
Junichi Takagi earned B.S. (1985), M.S. (1987), and Ph.D. (1990) from the Tokyo Institute of Technology with his studies on biochemical characterization of proteins implicated in hemostasis, particularly blood coagulation factors and platelet receptors. He continued to do research at the same institute as an Assistant Professor in the lab of Yuji Saito, where he discovered a new cell adhesion substrate against VLA-4 integrin. In 1996, he spent 6 months at the lab of Yoshi Takada at The Scripps Research Institute in La Jolla, USA, as a Japan Society for the Promotion of Science (JSPS) Visiting Research Fellow and studied structure-function relationship of integrin adhesion receptors. In 1998, he moved to the lab of Tim Springer at Harvard Medical School in Boston to expand the research expertise to the field of structural biology. This led to the publication of several major papers on integrin and related molecules. His discovery that integrin’s activity is governed by its conformational state at the cell surface changed the way we understand how cell’s adhesion behavior is regulated at the molecular level, and Takagi’s paper has been cited more than 1,400 times. At Harvard he was appointed an Assistant Professor in the Department of Pediatrics. In 2003 he returned to Japan as a Professor at the Institute for Protein Research, Osaka University.
During his career at Harvard (1998-2002) and Osaka University (2003-present), Professor Takagi’s research interest had always been centered on structural and functional analyses of receptor-ligand interactions, mainly through the structural study of receptor ectodomains and extracellular proteins, using both X-ray crystallography and electron microscopy. At the same time, his structural studies necessitated him to develop many new technologies to allow high quality protein production/purification. For example, he developed multiple peptide affinity tag systems that can rapidly purify unstable proteins from crude mixture. These include the TARGET tag with the ability to elute captured tagged proteins from the antibody resin under very mild conditions, and a PA tag that can achieve single-step purification of ultra-pure membrane protein. Due to the excellent purification compatibilities, both tag systems have been commercialized and are sold and used worldwide. Another example of the transition of his basic research outcome into a commercial product is the discovery of a protein stabilizer of Wnt protein, a very important but highly unstable stem cell growth factor. This has led to the development of a culture supplement that can be used to establish organoid cultures, and this supplement is now commercially available and widely used in labs and clinics, to obtain organoids from various normal and cancer tissues.
In 2015, Junichi Takagi started a very important collaboration with Hiroaki Suga of University of Tokyo, the inventor of a macrocyclic peptide discovery platform RaPID (Random non- standard Peptides Integrated Discovery) system. By combining his expertise on structural biology and protein engineering, he and Suga co-invented “Lasso Graft Technology” (hereinafter abbreviated as LG method). This is a technique for grafting the ability of a cyclic peptide to bind to a pharmaceutical target onto an unrelated protein. The LG method imparts the extremely high specificity and affinity for drug target proteins, which was previously possessed by the cyclic peptide, onto the scaffold protein. Using this technology, not only was it possible to create multi-specific antibodies (one antibody recognizing multiple antigens) in a short period of time, but also it became possible to confer novel binding activity to proteins that had never been considered as viable form of biopharmaceuticals (such as serum albumin). The LG method is expected to be implemented in an extremely wide range of fields, as it presents a new way of making biopharmaceuticals, rather than a tool to develop a particular drug for a specific disease. In 2017, Takagi and Suga co-founded MiraBiologics Inc., a bio-venture that develops pharmaceuticals based on this technology. The company is already collaborating with multiple Japanese and global major pharmaceutical companies and is proceeding with specific drug discovery projects. MiraBiologics is also developing several drugs for rare diseases in-house, through joint research between the founders and other academic researchers.
During his research career, Professor Takagi has published about 200 peer-reviewed original papers and has achieved an H-index of 68. He has filed about 15 patents, among which five (including two that are already granted) are on the technology being used by the MiraBiologics company. He has been invited to give lectures at numerous international conferences including Keystone Symposia and Gordon Research Conferences. He has also served as an external evaluator for several research institutes and academic appointment/promotion processes in foreign countries including USA, Germany, Singapore, and South Korea. His scientific contribution was acknowledged by receiving prizes such as the President’s Excellent Research Awards (2013, 2014) by Osaka University, and the JSGCT Award for Outstanding Research in Gene Therapy (2021) by the Japanese Society for Gene and Cell Therapy. Professor Takagi’s research has always been focused on solving basic biological questions – at the same time, he has shown strong entrepreneurship through making numerous innovative inventions.