Toyomasa Katagiri

Director
​​National Institutes of Biomedical Innovation, Health and Nutrition

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Dr. Toyomasa Katagiri was obtained MSc. from an MSc from Kagawa University, Faculty of Agriculture, followed by a Ph.D. from Osaka University School of Medicine. In the early stages of his career, Dr. Katagiri served as a Research Associate at Otsuka Pharmaceutical Co., Ltd.. His passion for cancer research led him to the Japanese Foundation for Cancer Research, where he held positions in the Department of Biochemistry and the Department of Human Genome Analysis at the Cancer Institute. These roles from 1992 to 1998 were pivotal in establishing his long-term research in cancer genomics, especially identification of breast cancer susceptibility genes.  

Dr. Katagiri's international experience was augmented during his tenure as a Postdoctoral Fellow at the Department of Medical and Molecular Genetics, Division of Genetics and Development, at King's College London’s Guy's, Kings, and St Thomas' School of Medicine, where he expanded his expertise in cancer genetics. Upon returning to Japan, he contributed to the University of Tokyo's Human Genome Center as an Assistant Professor, later becoming an Associate Professor, highlighting his growing reputation in cancer genomic research. 

Dr. Katagiri's academic leadership further blossomed at The University of Tokushima. As a Professor at the Division of Genome Medicine, Institute for Genome Research from 2008 to 2016, and continuing in this role at the Institute of Advanced Medical Sciences, his work has been instrumental in cancer drug discovery and its clinical applications through comprehensive cancer genomics. In 2020, Dr. Katagiri was appointed as the Director of the Institute of Advanced Medical Sciences at Tokushima University, overseeing a crucial period of innovation and research expansion. As of 2023, Dr. Katagiri has assumed a Director of the National Institute of Biomedical Innovation, National Institutes of Biomedical Innovation, Health, and Nutrition. 

For his accomplishment, he received the young investigator awards of the Japanese Cancer Association, and many research funds that includes Princess Takamatsu Cancer Research Fund, and Kobayashi Foundation for Cancer Research, SGH Cancer Research Grant, and the Naito Foundation Research Gant.

Speech title & Synopsis

Development of Peptide-Based PPI Inhibitor Targeting the BIG3-PHB2 cancer specific complex for Breast Cancer

Approximately 70% of breast cancer cases exhibit estrogen receptor alpha (ERα) expression. Current endocrine therapies mainly target the estrogen (E2)/ERα signaling pathway with selective ERα modulators, ERα downregulators, and aromatase inhibitors. However, their efficacy is compromised due to high rates of intrinsic and acquired resistance. Thus, the identification of resistance factors and pathways, and the development of novel treatments are imperative. We have focused on the tumor suppressor Prohibitin 2 (PHB2). Although PHB2 is frequently overexpressed in breast cancers without somatic mutations or epigenetic alterations, the inactivation mechanism of PHB2 was still puzzled in cacner cells. We previously showed that the cancer-specific scaffold protein BIG3 inhibits E2-dependent phosphorylation of PHB2 by direct interaction, crucial for ERα transcriptional activity, leading to continuous E2 signaling activation in breast cancer cells. Crucially, BIG3 levels correlate significantly with poor prognosis. We developed a stapled peptide inhibitor, ERα Activity-Regulator Synthetic Peptide (stERAP), targeting the BIG3-PHB2 interaction, harnessing PHB2's tumor-suppressive properties. stERAP specifically disrupts the BIG3-PHB2 interaction, imparting durable suppressive effects on E2-induced tumor progression in xenograft mice bearing ERα-positive breast cancer cells through weekly intravenous administration. Preclinical testing showed no adverse effects in cynomolgus monkeys and rats. Notably, the BIG3-PHB2 complex localizes to the cytoplasm in ERα-positive cells but relocates under the plasma membrane in tamoxifen-resistant ERα-positive cells. Remarkably, in tamoxifen-resistant cells, stERAP disrupts the membrane-associated BIG3-PHB2 complex, restoring the tumor-suppressive function of PHB2 at the membrane and overcoming tamoxifen resistance. This presentation will detail the antitumor efficacy of stERAP in breast cancer and its potential applicability across various cancer types.