- Elucidating the mechanism of large-scale intracellular degradation by autophagy using specific membrane dynamics
- Investigating the involvement of autophagy in various disease states
- Elucidating the mechanism of lifespan extension by autophagy
- Development of therapeutic strategies targeting autophagy
By using a multidisciplinary approach including imaging, cell engineering, molecular biology and biochemistry, the lab aims to clarify the molecular mechanism of autophagy and how to control it
The main research focus of the laboratory is autophagy, a process in which cytoplasmic substances are encapsulated by a membrane structure, the autophagosome, and transported to lysosomes (Fig. 1). Although the discovery of autophagy dates back to the 1950s, its molecular basis remained unknown for a long time. This situation was broken down in 1993 by Yoshinori Ohsumi, Professor of Tokyo Institute of Technology. Dr. Osumi was awarded the 2016 Nobel Prize for Physiology Medicine, for this work, which led to great insights on the physiological and pathological importance of autophagy became clear.
The autophagy field has developed dramatically in the last decade, and many studies are now focusing on its function in mammals. Autophagy maintains cell homeostasis by degrading cellular components and is thought to have a protective effect against a wide range of diseases such as infectious diseases, nephropathy, fatty liver, inflammatory diseases, neurodegenerative diseases, carcinogenesis, and heart failure among others. Its function is also attributed to extending our life spans. Professor Yoshimori joined the the Osumi Laboratory in 1996, where he extended autophagy research to mammalian systems. For example, he identified the autophagosome binding protein LC3 and developed imaging systems to observe autophagy kinetics. The number of cited citations in this paper is over 4,000 and is ranked first in the field. More recently, we have shown that the contact site of the endoplasmic reticulum and mitochondria is the place of formation of autophagosomes, which had been controversial in the field. We also reported that autophagy can remove pathogenic bacteria from the cell (Fig. 2). In collaboration with the nephrology department, we have also found autophagy can selectively remove damage lysosomes, providing a potential mechanism to explain the prevention of hyperuricemia. In collaboration with the department of gastroenterology, we found that higher levels of the autophagy suppressor Rubicon were the main cause of nonalcoholic fatty liver development due to high fat dietary intake. Currently, we are investigating the molecular mechanisms of autophagy, which is expected to have a strong relationship with many pathologies and aid in the development of new treatment strategies.