Structure, lipid scrambling activity and role in autophagosome formation of ATG9A. Maeda, S., Yamamoto, H., Kinch, L.N., Garza, C.M., Takahashi, S., Otomo, C., Grishin, N.V., Forli, S., Mizushima, N., Otomo, T.# Nat. Struct. Mol. Biol., 2020, 27, 1194-1201.
Investigators
Takanori Otomo, Ph.D.
Research Focus
Dr. Otomo received an undergraduate degree in chemistry from Osaka University in Japan in 1996. He received his Ph.D. in protein bioscience from Osaka University in 2001. Under the guidance of Dr. Toshio Yamazaki, he developed an intein-mediated protein labeling method. He also determined the structure of the apoptotic caspase-activated DNase in complex with its inhibitor. He then obtained a Human Frontier Science Program Long-Term Fellowship to join the laboratory of Dr. Michael Rosen at Memorial Sloan-Kettering Cancer Center in New York in 2001.
Along with the Rosen lab, he moved to the University of Texas Southwestern Medical Center at Dallas later in the same year. At Dallas, he elucidated the molecular mechanisms of actin regulation by formin proteins. In 2007, Dr. Otomo started his independent laboratory as Assistant Professor in the Department of Molecular Biology at The Scripps Research Institute in La Jolla. He was promoted to Associate Professor in 2018 in the Department of Integrative Structural and Computational Biology at Scripps. He joined SDBRI in early 2022.
The Otomo lab aims to understand the mechanism of autophagy, the lysosome-dependent bulk degradation process in cells. The hallmark of autophagy is the de novo formation of the membrane compartment termed autophagosome in the cytoplasm. Cytoplasmic materials, including harmful protein aggregates and dysfunctional organelles, are sequestered into the autophagosome and broken down in a lysosome upon the fusion between the autophagosome and the lysosome. Autophagy is crucial for maintaining cellular health and fighting against pathogens. Its defects are closely linked to human health and diseases, such as neurodegeneration, cancer, infections, and aging.
The Otomo lab combines structural biology, biochemistry, and cell biology to determine the functions of core autophagy-related (ATG) proteins. The lab’s achievements include the structural basis for the lipid conjugation of the autophagic ubiquitin-like protein ATG8, the identification of the lipid transfer function of ATG2, and the discovery and the structural basis of the lipid scrambling activity of ATG9 membrane protein. The lab now seeks to define the overall mechanism of autophagosome biogenesis based on the obtained mechanistic information. The lab is also developing rational strategies to intervene in autophagy for curing neurodegenerative disorders and cancer.
Education
Ph.D. in Protein Bioscience, Osaka University, 2001
M.Sc. in Chemistry, Osaka University, 1998
B.Sc. in Chemistry, Osaka University, 1996
Professional Experience
2022 – Present, Current Associate Professor, San Diego BioMed
2018 – 2022 Associate Professor, Department of Integrative Structural & Computational Biology, The Scripps Research Institute
2013 – 2018 Assistant Professor, Department of Integrative Structural & Computational Biology, The Scripps Research Institute
2007 – 2012 Assistant Professor, Department of Molecular Biology, The Scripps Research Institute
2001 – 2007 Postdoctoral Fellow, University of Texas Southwester Medical Center
2001 – 2001 Postdoctoral Fellow, Memorial Sloan-Kettering Cancer Center
Select Publications
The autophagic membrane tether ATG2A transfers lipids between membranes. Maeda, S., Otomo, C., Otomo, T.# eLife, 2019, 8. pii: e45777.
Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2A-WIPI4 complex. Chowdhury, S.*, Otomo, C.*, Leitner, A., Ohashi, K., Aebersold, R., Lander, G.C.#, Otomo, T.# Proc. Natl. Acad. Sci. USA. 2018, 115, E9792-E9801
Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Otomo, C., Metlagel, Z., Takaesu, G., Otomo, T.# Nat. Struct. Mol. Biol. 2013, 20, 59-66.
Structural basis of ATG3 recognition by the autophagic ubiquitin-like protein ATG12. Metlagel, Z., Otomo, C., Takaesu, G., Otomo, T.# Proc. Natl. Acad. Sci. USA. 2013, 110, 18844-9.
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