Keio University

1: Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival

Science of the Month - June 2018

Nat Commun.

2018 Apr 19;9(1):1561. doi: 10.1038/s41467-018-03899-1.

Megumi Shiota, Masayuki Naya, Takehiro Yamamoto, Takako Hishiki, Takeharu Tani, Hiroyuki Takahashi, Akiko Kubo, Daisuke Koike, Mai Itoh, Mitsuyo Ohmura, Yasuaki Kabe, Yuki Sugiura, Nobuyoshi Hiraoka, Takayuki Morikawa, Keiyo Takubo, Kentaro Suina, Hideaki Nagashima, Oltea Sampetrean, Osamu Nagano, Hideyuki Saya, Shogo Yamazoe, Hiroyuki Watanabe, Makoto Suematsu

A research group from the Department of Biochemistry, Keio University School of Medicine, including Guest Professor Makoto Suematsu (62nd graduating class), part-time lecturers Megumi Shiota and Masayuki Naya, and full-time lecturers Takehiro Yamamoto, Takako Hishiki, and Yasuaki Kabe, has successfully developed a method to automatically visualize the location of cancer without labels or stains. By developing a special substrate coated with gold nanoparticles, the team used Surface-enhanced Raman Spectroscopy imaging (SERS imaging) to detect "interatomic vibrations" from numerous metabolites in cancerous and non-cancerous regions of frozen mouse pathological tissue sections. They then statistically analyzed the differences in the metabolic profiles of these two regions to identify the cancer. Cancer cells are rich in "sulfur-containing functional molecules" involved in the regulation of cell proliferation and cell death. These molecules interact with the gold nanoparticles, generating Raman scattered light that reflects their unique interatomic vibrations. This study demonstrated that in addition to detecting existing antioxidant molecules like glutathione, it is also possible to detect and visualize an abundance of functional molecules called polysulfides, which are generated from hydrogen sulfide, in cancerous tissue. While conventional pathological diagnosis has primarily relied on methods based on identifying the morphological features of cells and nuclei, this research opens up the possibility of distinguishing between cancerous and non-cancerous areas through a biochemical qualitative diagnosis under label-free and stain-free conditions.

(Makoto Suematsu, Guest Professor, Department of Biochemistry, 62nd graduating class)

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2: Two Classes of Secreted Synaptic Organizers in the Central Nervous System

ANNUAL REVIEW OF PHYSIOLOGY

2018, VOL 80, 80 243-262; 10.1146

Yuzaki, Michisuke

The lab members who contributed to this achievement

In the human brain, approximately 100 billion neurons connect via as many as 1,000 trillion synapses to form neural circuits. Synapses are not only determined by genes but also change throughout life in response to neural activity. As a result of recent genomic and brain imaging studies, many psychiatric and neurological disorders and developmental disabilities, such as Alzheimer's disease, schizophrenia, and autism spectrum disorder, are increasingly considered to be "synaptopathies" caused by synaptic dysfunction. Therefore, elucidating how synapses are formed, maintained, and lost in pathological processes is a critical issue not only for basic science but also for clinical medicine. The molecules that regulate synapse formation were largely known to be cell adhesion molecules (e.g., Neurexin) and secreted (diffusible) molecules (e.g., Wnt). The former act at close range to promote synaptic maturation, while the latter diffuse over long distances to promote synapse formation. Recently, extracellular scaffold proteins (e.g., Cbln1), which are secreted and then remain in the synaptic cleft to serve as a scaffold for various molecules, have been gaining attention as a third category. This review summarizes recent findings and discusses these two types of secreted molecules.

(Michisuke Yuzaki, Professor, Department of Physiology, equivalent to the 64th graduating class)

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Other Publications

1: Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis

GASTROENTEROLOGY,

154 (4):935-947; 10.1053/j.gastro.2017.11.024 MAR 2018

Naganuma M, Sugimoto S, Mitsuyama K, Kobayashi T, Yoshimura N, Ohi H, Tanaka S, Andoh A, Ohmiya N, Saigusa K, Yamamoto T, Morohoshi Y, Ichikawa H, Matsuoka K, Hisamatsu T, Watanabe K, Mizuno S, Suda W, Hattori M, Fukuda S, Hirayama A, Abe T, Watanabe M, Hibi T, Suzuki Y, Kanai T

2: Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence during Disease Progression

CELL STEM CELL,

22 (3):454-+; 10.1016/j.stem.2017.12.009 MAR 1 2018

Seino Takashi, Kawasaki Shintaro, Shimokawa Mariko, Tamagawa Hiroki, Toshimitsu Kohta, Fujii Masayuki, Ohta Yuki, Matano Mami, Nanki Kosaku, Kawasaki Kenta, Takahashi Sirirat, Sugimoto Shinya, Iwasaki Eisuke, Takagi Junichi, Itoi Takao, Kitago Minoru, Kitagawa Yuko, Kanai Takanori, Sato Toshiro

3: Novel polyubiquitin imaging system, PolyUb-FC, reveals that K33-linked polyubiquitin is recruited by SQSTM1/p62

AUTOPHAGY,

14 (2):347-358; 10.1080/15548627.2017.1407889 2018

Nibe, Yoichi; Oshima, Shigeru; Kobayashi, Masanori; Maeyashiki, Chiaki; Matsuzawa, Yu; Otsubo, Kana; Matsuda, Hiroki; Aonuma, Emi; Nemoto, Yasuhiro; Nagaishi, Takashi; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Nakada, Shinichiro; Watanabe, Mamoru