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Organized by
Nano Life Science Institute of Kanazawa University
Cancer Research Institute of Kanazawa University

Co-Organized by
Institute for Frontier Science Initiative of Kanazawa University
Kanazawa Association of Tumor Biologists

Symposium Website
https://nanolsi.kanazawa-u.ac.jp/en/4th-sympo/

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4th

NanoLSI Symposium- Bio-imaging, sensing and manipulation for medical science -International Symposium on Tumor Biology
in Kanazawa2020
November 26-27, 2020
- Vanue -OnlinePROGRAMME
Session1

8:00 am-8:30 am (JST), Nov. 26
12:00 am-12:30 am (CET), Nov. 26
6:00 pm-6:30 pm (EST), Nov. 25

Simon SCHEURING

2

8:30 am-9:00 am (JST), Nov. 26
12:30 am-1:00 am (CET), Nov. 26
6:30 pm-7:00 pm (EST), Nov. 25

Yusuke MIYANARI

3

9:00 am-9:30 am (JST), Nov. 26
1:00 am-1:30 am (CET), Nov. 26
7:00 pm-7:30 pm (EST), Nov. 25

Kenneth S. ZARET
Professor
University of Pennsylvania

Two-Parameter, Single-Molecule-Tracking Assessments
Discriminate Diverse Regulatory Factor Behaviors in
Chromatin

4

9:30 am-10:00 am (JST), Nov. 26
1:30 am-2:00 am (CET), Nov. 26
7:30 pm-8:00 pm (EST), Nov. 25

Takanori TAKEBE

Promise and Impact of Organoid Medicine

Professor
Weill Cornell Medicine

Associate Professor
WPI-NanoLSI / CRI

P6

Simon SCHEURING

P8

Yusuke MIYANARI

Nano Life Science Institute
Cancer Research Institute, Kanazawa University

P10

Kenneth S. ZARETUniversity of Pennsylvania

P12

Takanori TAKEBETokyo Medical and Dental University

P14

Tomoki OGOSHI

Kyoto University
Nano Life Science Institute, Kanazawa University

Printed Nanofilm to Engineer Bioelectronic “Second
Skin”

P16

Toshinori FUJIE

Tokyo Institute of Technology

CUBIC-HistoVIsion: a versatile three-dimensional
whole-organ/body staining and imaging based onelectrolyte-gel properties of biological tissue

P18

Etsuo SUSAKI

P20

Susumu KITAGAWA

P22

Nobuo NODA

P24

Noriyuki KODERA

Nano Life Science Institute, Kanazawa University

P26

Shinji WATANABE

Nano Life Science Institute, Kanazawa University

P28

Victor SHAHIN

P30

Keehoon JUNG

P32

Takeshi IMAMURA

P34

Ann-Marie CHACKO

Duke-NUS Medical School

P36

Masanobu OSHIMA

Nano Life Science Institute
Cancer Research Institute, Kanazawa University

Toward understanding transcriptional events deep inside
the chromatin jungle

Chemistry-Driven Challenges: from Molecule to Nano/Microscale
Chair: Satoshi ARAI ( Associate Professor / WPI-NanoLSI )1

Tomoki OGOSHI

2

2:00 pm-2:30 pm (JST), Nov. 26
6:00 am-6:30 am (CET), Nov. 26
12:00 am-12:30 am (EST), Nov. 26

Toshinori FUJIE

3

2:30 pm-3:00 pm (JST), Nov. 26
6:30 am-7:00 am (CET), Nov. 26
12:30 am-1:00 am (EST), Nov. 26

Etsuo SUSAKI

4

3:00 pm-3:30 pm (JST), Nov. 26
7:00 am-7:30 am (CET), Nov. 26
1:00 am-1:30 am (EST), Nov. 26

Susumu KITAGAWA

Professor
Kyoto University / WPI-NanoLSI

Associate Professor (Lecturer)
Tokyo Institute of Technology

Associate Professor
The University of Tokyo

Distinguished Professor
Kyoto University

Supramolecular Assemblies of Pillar[n]arenes for
Molecular Separation, Artificial Water Channels andBiosensor Applications

Weill Cornell Medicine

1

Nobuo NODA2

5:30 pm-6:00 pm (JST), Nov. 26
9:30 am-10:00 am (CET), Nov. 26
3:30 am-4:00 am (EST), Nov. 26

Noriyuki KODERA

3

6:00 pm-6:30 pm (JST), Nov. 26
10:00 am-10:30 am (CET), Nov. 26
4:00 am-4:30 am (EST), Nov. 26

Shinji WATANABE

4

6:30 pm-7:00 pm (JST), Nov. 26
10:30 am-11:00 am (CET), Nov. 26
4:30 am-5:00 am (EST), Nov. 26

Victor SHAHINLaboratory Head
Institute of Microbial Chemistry

Professor
WPI-NanoLSI

Associate Professor
WPI-NanoLSI

Professor
University of Münster

Autophagy regulation by liquid-liquid phaseseparation
Single-molecule visualization of intrinsicallydisordered Rett syndrome protein, MeCP2 by highspeed Atomic Force Microscopy
Probing and characterizing nano-bio interfaces byscanning ion conductance microscopy
Facilitating nuclear delivery of pharmacological
nanoparticles by interfering with the selective nuclear
pore barrier

Imaging Approaches to Explore Cancer Biology
Chair: Masanobu OSHIMA ( Professor / WPI-NanoLSI / CRI )1

10:00 am-10:30 am (JST), Nov. 27
2:00 am-2:30 am (CET), Nov. 27
8:00 pm-8:30 pm (EST), Nov. 26

Keehoon JUNG

2

10:30 am-11:00 am (JST), Nov. 27
2:30 am-3:00 am (CET), Nov. 27
8:30 pm-9:00 pm (EST), Nov. 26

Takeshi IMAMURA

3

11:00 am-11:30 am (JST), Nov. 27
3:00 am-3:30 am (CET), Nov. 27
9:00 pm-9:30 pm (EST), Nov. 26

Ann-Marie CHACKO

4

11:30 am-12:00 pm (JST), Nov. 27
3:30 am-4:00 am CET), Nov. 27
9:30 pm-10:00 pm (EST), Nov. 26

Masanobu OSHIMA

Assistant Professor
Seoul National University College of Medicine

Professor
Ehime University

Assistant Professor
Duke-NUS Medical School

Professor
WPI-NanoLSI / CRI

The University of Tokyo

New Dimensions of Porous Coordination Polymers/
Metal-Organic Frameworks

Nano-Scale Approaches to Physiological and Pathological Phenomena
Chair: Toshio ANDO ( Professor / WPI-NanoLSI )5:00 pm-5:30 pm (JST), Nov. 26
9:00 am-9:30 am (CET), Nov. 26
3:00 am-3:30 am (EST), Nov. 26

Session4

High-Speed Atomic Force Microscopy: A Forceful Tool for
Molecular Biophysics

Professor
Tokyo Medical and Dental University

1:30 pm-2:00 pm (JST), Nov. 26
5:30 am-6:00 am (CET), Nov. 26
11:30 pm-12:00 am (EST), Nov. 25

Session3

4

Molecular and Cellular Dynamics in Biological Regulation and Regenerative Medicine
Chair: Kunio MATSUMOTO ( Professor / WPI-NanoLSI / CRI )1

Session2

ORAL PRESENTATION

Kyoto University

Institute of Microbial Chemistry

University of Münster

Seoul National University College of Medicine

Real-time intravital characterization of non-classicalmonocytes in cancers
Development of in vivo cancer imaging techniqueby advanced multi-photon laser excitation
microscopy
Developing novel probes for in vivo molecular PET imaging
of cancer immunotherapy
Polyclonal metastasis of colorectal cancer

Ehime University

5

Simon SCHEURING
Department of Anesthesiology, Department of Physiology and Biophysics
Weill Cornell Medicine, USA

High-Speed Atomic Force Microscopy:
A Forceful Tool for Molecular Biophysics

Contact : sis2019 [at sign] med.cornell.edu
Please replace [at sign] with @.

Simon SCHEURING
Department of Anesthesiology, Department of Physiology and Biophysics, Weill Cornell Medicine, USA

High-speed atomic force microscopy (HS-AFM)[1] is a powerful technique that

Research Interests

provides dynamic movies of biomolecules at work. HS-AFM has the notable

Membrane protein, Structure, Conformational changes, Atomic Force Microscopy, Force Spectroscopy

environmental cues such as changes of pH, ions, ligands, temperature, light andadvantage that it per mits to subject the proteins under investigation toforce. This is particularly advantageous for the study of ion channels that respondto a wide range of stimuli [2], and transporters with substrate-dependent activities.

Education Professional Career

To break current temporal limitations to characterize molecular dynamics using HS-

1997 - 2001

PhD thesis: Summa cum laude, Biozentrum, University Basel, Switzerland(HS-AFM-HS), a technique whereby we oscillate the HS-AFM tip at a fixed position

2001 - 2003
2004 - 2007

Postdocs: University Basel, Switzerland (2001), Institut Curie, Paris, France (2002, 2003)

2001 - 2005
2007 - 2012

Habilitation (HDR), Université Pierre et Marie Curie, Paris 6, Jussieu, Paris, France

2010 - 2011

Director INSERM U1006, Institut Curie, Paris, France

2012 - 2016

DR1 INSERM – Senior Research Director, INSERM

2012 - 20162017 - present

Director INSERM U1006, INSERM/Aix-Marseille Université, Marseille, France

CR2 INSERM – Researcher, Institut Curie, Paris, France

us to determine the dynamics of individual unlabeled amino acid transporters at
millisecond temporal resolution [4].

HS-AFM frames and schematic of aminoacid transporter GltPh in membrane.

Top: HS-AFM line scanning kymograph with 3.3ms temporal resolution of GltPh transport motion.
Bottom: Height/time trace and idealized state assignment (red).

Professor, Weill Cornell Medicine, Anesthesiology, Physiology & Biophysics, NY, USA

References

Atomic Force Microscopy application and development[ 1 ] A high-speed atomic force microscope for studying biological macromolecules, PNAS, 2001, 98(22):12468-12472,
doi.org/10.1073/pnas.211400898, Toshio Ando, Noriyuki Kodera, Eisuke Takai, Daisuke Maruyama, Kiwamu Saito,
and Akitoshi Toda

Honors2019 - 2024
2012 - 20172006 - 2010

and detect the motions of the molecules under the tip [3]. These methods allowed

DR2 INSERM – Junior Research Director

Scientific Activities
1995 - present

AFM, we use HS-AFM line scanning (HS-AFM-LS) and HS-AFM height spectroscopy

NIH Director's Pioneer Award (DP1)ERC Starting/Consolidator Grant 2012
INSERM Avenir 2005 Program Awardee

Publications
Millisecond dynamics of an unlabeled amino acid transporter, Nature Communications, 2020, 11(5016), doi.org/10.1038/s41467-020-18811-z, TR

1. Matin#, GR Heath#, GHM Huysmans, O Boudker & S Scheuring[ 2 ] Force-induced conformational changes in Piezo1, Nature, 2019, 573(7773):230–234, doi. 10.1038/s41586-0191499-2, Yi-Chih Lin, Yusong R Guo, Atsushi Miyagi, Jesper Levring, Roderick MacKinnon & Simon Scheuring[ 3 ] High-Speed AFM Height Spectroscopy (HS-AFM-HS): Microsecond dynamics of unlabeled biomolecules, Nature
Communications, 2018, 9(1):4983. doi:10.1038/s41467-018-07512-3, George Heath & Simon Scheuring[ 4 ] Millisecond dynamics of an unlabeled amino acid transporter, Nature Communications, 2020, 11(5016), doi.
org/10.1038/s41467-020-18811-z, Tina R Matin, George R Heath, Gerard HM Huysmans, Olga Boudker & Simon
Scheuring

Force-induced conformational changes in Piezo1, Nature, 2019, 573(7773):230–234, doi. 10.1038/s41586-019-1499-2, Y-C Lin#, YR Guo#, A Miyagi, J

2. Levring, R MacKinnon* & S Scheuring

High-Speed AFM Height Spectroscopy (HS-AFM-HS): Microsecond dynamics of unlabeled biomolecules, Nature Communications, 2018, 9(1):4983.

3. doi:10.1038/s41467-018-07512-3, GR Heath & S Scheuring

6

7

Yusuke MIYANARI
Nano Life Science Institute (WPI-NanoLSI),
Cancer Research Institute, Kanazawa University, Japan

Toward understanding transcriptional events deep
inside the chromatin jungle

Contact : miyanari [at sign] staff.kanazawa-u.ac.jp

Yusuke MIYANARI

Please replace [at sign] with @.

Nano Life Science Institute (WPI-NanoLSI),
Cancer Research Institute, Kanazawa University, Japan

Research Interests

Chromatin is organized in a non-random fashion within 3D nuclear space. During developmental processes, the nuclear

Epigenetics, Stem cell, chromatin, transcription

structural components of the nucleus are responsible for developmental aberrations and several human diseases. Remodelingarchitecture is dramatically reconstructed, resulting in the establishment of cell-type specific nuclear organization. Defects inof the nuclear architecture leads to spatial arrangement of genes, which could affect genome functions including gene
expression. We aim to reveal the role of chromatin dynamics in cell lineage-allocation by deciphering the molecular

Education
2006

mechanisms underlying the remodeling of nuclear organization and their effects on developmental gene expression, using
mouse early embryos and embryonic stem (ES) cells as model systems. We uncovered allelic regulation of key gene for
PhD, Department of Human Tumor Viruses, Graduate School of Biostudies, Kyoto University

reprogramming, Nanog, is crucial for cell-lineage allocation in early mouse embryos [1,2]. We also studied a role of PML
bodies in transcriptional regulation in ES cells [3]. In this seminar, I will present our recent studies to show you how we tackle
our questions.

Professional Career

The promyelocytic leukemia (PML) body is a phase-separated nuclear structure physically associated with chromatin, implying

2006 - 2009

Postdoc, National Institute of Genetics (NIG), JAPAN

mediated chromatin labeling and purification (ALaP) to identify the genomic regions proximal to PML bodies. We found that2009 - 2014

Postdoc, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Strasbourg, FRANCE

2014 - 2020

Associate Professor (PI), National Institute of Basic Biology (NIBB), JAPAN2020 - present

Associate Professor (PI), NanoLSI, Kanazawa University.

its crucial roles in genome functions. However, its role in transcriptional regulation is largely unknown. We developed APEXPML bodies associate with active regulatory regions across the genome and with ~300 kb of the short arm of the Y
chromosome (YS300) in mouse embryonic stem cells. The PML body association with YS300 is essential for the transcriptional
activity of the neighboring Y-linked clustered genes. Mechanistically, PML bodies provide specific nuclear spaces that the denovo DNA methyltransferase DNMT3A cannot access, resulting in the steady maintenance of a hypo-methylated state at
Y-linked gene promoters. Our study underscores a new mechanism for gene regulation in the 3D nuclear space and provides
insights into the functional properties of nuclear structures for genome function.

Scientific Activities
2001 - 2006
2006 - present

Studies on Hepatitis C virus
Epigenetic regulation of cell lineage allocation

Honors2015
2015

The Young Scientists’ Prize, The Commendation for Science and Technology by the MEXT
Takenaka Promotion Prize

Publications
1. Miyanari Y, Torres-Padilla ME, Control of ground-state pluripotency by allelic regulation of Nanog, Nature, 483.470-473. 2012.
Miyanari Y*, Birling CZ. And Torres-Padilla ME*, Live visualization of chromatin dynamics using fluorescent TALEs, Nature Structural & Molecular Biolo-

2. gy, 2013. *Corresponding authors
3.

Kurihara M, Miyanari Y, et al., Genomic profiling of PML bodies reveals transcriptional regulation by PML bodies through the DNMT3A exclusion,
Molecular Cell, 2020, Volume 78, Issue 3, 7 May 2020, Pages 493-505.e8.

References[ 1 ] Miyanari Y, Torres-Padilla ME, Control of ground-state pluripotency by allelic regulation of Nanog, Nature,
483.470-473. 2012.
[ 2 ] Miyanari Y*, Birling CZ. And Torres-Padilla ME*, Live visualization of chromatin dynamics using fluorescent TALEs,
Nature Structural & Molecular Biology, 2013. *Corresponding authors[ 3 ] Kurihara M, Miyanari Y, et al., Genomic profiling of PML bodies reveals transcriptional regulation by PML bodies
through the DNMT3A exclusion, Molecular Cell, 2020, Volume 78, Issue 3, 7 May 2020, Pages 493-505.e8.

89

Kenneth S. ZARETInstitute for Regenerative Medicine (IRM)
University of Pennsylvania, USA

Two-Parameter, Single-Molecule-Tracking Assessments
Discriminate Diverse Regulatory Factor
Behaviors in Chromatin

Contact : zaret [at sign] pennmedicine.upenn.edu
Please replace [at sign] with @.

Kenneth S. ZARETInstitute for Regenerative Medicine, University of Pennsylvania, USA

Research Interests

Our laboratory is interested in the ways that transcription factors initiate cell fate changes in embryonicTranscription factor-chromatin interactions, heterochromatin, cell reprogramming,

development, cell reprogramming, and human diseases such as cancer. We discovered that a certain class of gene
regulatory proteins, which we called "pioneer transcription factors," initiate cell fate changes by their ability totarget DNA sequences that are wrapped on a nucleosome at silent genes in cellular chromatin [1]. The initial

Education
1982
1982-1985

targeting of nucleosomal DNA by a pioneer factor causes an exposure of the underlying nucleosome [2], thus
PhD, Biophysics, University of Rochester Medical School, Rochester, NY
Postdoctoral fellowship, Biochemistry and Biophysics, University of California, San Francisco. CA

allowing cooperating transcription factors, co-regulators, and ATP-dependent nucleosome remodelers to access the
DNA and activate the targeted gene. Yet recent studies have shown that silent genes can exist in various states ofcompaction in chromatin, and pioneer factors have differential access to different types of silenced chromatin. To
better understand these issues, our laboratory employed HALO-tags on diverse chromosomal proteins andProfessional Career
1986- 1999

Professor, Cell, Molecular, and Developmental Biology, Brown University, RI

1999 - 2009

Senior Member, Program Leader, Cell and Dev. Biology Program, Fox Chase Cancer Ctr., PA

2009 - present

Professor and Director, IRM, Perelman School of Medicine, University of Pennsylvania, PA

transcription factors, which enabled single-molecule-tracking (SMT) of the individual molecules in real time, as themolecules diffuse in, or bind to, different chromatin domains in the nucleus of living cells. We began by using SMTof core histone proteins and quantified two parameters of molecular movement tracks over millisecond time scales[3]. We plotted the radius of confinement, which estimates the area in which the molecule performs its confined
motions, against the average displacement, representing the average distance between subsequent steps in a
motion track, over time. The two parameters, though generally positively correlated, present deviations that resolve
five mobility types for core histones with distinct subnuclear localizations. As expected, the mobility of diverse
heterochromatin proteins correlates with lower mobility chromatin, with notable differences that relate to particular

Scientific Activities
1986 - present

Signaling control of cell fate in embryonic development, cell reprogramming

1993 - present

Discovery and mechanism of action of pioneer transcription factors

2012 - present

Biophysical methods, proteomics to understand compacted heterochromatin chromatin2017 - present

Single-molecule-tracking to understand how transcription factors scan genomic chromatinbiochemical features of the proteins. Upon assessing the mobility of diverse transcription factors, we found that
pioneer factors with nucleosome binding ability can access the lowest mobility chromatin domains. Using welldefined mutations of the pioneer factor FOXA1, we found that nonspecific DNA/nucleosome binding and histoneinteractions are essential for scanning compacted chromatin. Our two-parameter SMT approach reveals how gene
regulatory proteins scan the genome during cell fate changes.

References

Honors
2002

Hans Popper Basic Science Award, Amer. Assoc. for the Study of Liver Diseases, ALF

2007

Elected as a Fellow of the American Assoc. for the Adv. of Science2017

Stanley N. Cohen Biomedical Research Award, Univ. Penn.

Publications
Zaret, K.S. (2020) Pioneer transcription factors initiating gene network changes. Annual Review of Genetics, (e-pub: https://doi.org/10.1146/

1. annurev-genet-030220-015007).

[ 1 ] Zaret, K.S. (2020) Pioneer transcription factors initiating gene network changes. Annual Review of Genetics,(e-pub: https://doi.org/10.1146/annurev-genet-030220-015007).
[ 2 ] Iwafuchi, M., et al. (2020) Gene network transitions in embryos depend upon interactions between a pioneer
transcription factor and core histones. Nature Genetics 52, 418-427. PMID:32203463[ 3 ] Lerner, J., Gomez-Garcia, P.A., McCarthy, R., Liu, Z., Lakadamyali, M., and Zaret, K.S. (2020) Two-parameter
mobility assessments discriminate diverse regulatory factors behaviors in chromatin. Molecular Cell 79, 418-5427.
PMID: 32574554

Iwafuchi, M., Cuesta, I., Donahue, G, Takenaka, N. Osipovich, A.B., Magnuson, M. A., Roder, H., Seeholzer, S.H., Santisteban, P., and Zaret, K.S. (2020)

2. Gene network transitions in embryos depend upon interactions between a pioneer transcription factor and core histones. Nature Genetics 52,
418-427. PMID:32203463

Lerner, J., Gomez-Garcia, P.A., McCarthy, R., Liu, Z., Lakadamyali, M., and Zaret, K.S. (2020) Two-parameter mobility assessments discriminate diverse

3. regulatory factors behaviors in chromatin. Molecular Cell 79, 418-5427. PMID: 32574554
1011

Takanori TAKEBE

Promise and Impact of Organoid Medicine

Institute of Research, Tokyo Medical and Dental University, Japan
Communication Design Center, Yokohama City University, Japan
Division of Gastroenterology, Hepatology and Nutrition and Division of
Developmental Biology, Cincinnati Children's Hospital Medical Center, USA

Takanori TAKEBE
Institute of Research, Tokyo Medical and Dental University, Japan
Communication Design Center, Yokohama City University, Japan
Division of Gastroenterology, Hepatology and Nutrition and Division of Developmental Biology,

Contact : ttakebe.ior [at sign] tmd.ac.jp

Cincinnati Children's Hospital Medical Center, USA

Please replace [at sign] with @.

Research Interests
Stem cell and developmental biology, organoid medicine

organoids range from simple epithelial structures to complex, disorganized tissues with large cellular diversity. The
current challenge is to engineer cellular complexity into organoids in a controlled manner that results in organizedassembly and acquisition of tissue function. These efforts have relied on studies of organ assembly during embryonicdevelopment and have resulted in development of organoids with multilayer tissue complexity and higher order

Education
2011
2019

Organoids are multicellular structures that can be derived from adult organs or pluripotent stem cells. Early versions offunctions. For example, we show that antero-posterior interactions recapitulate the foregut and the midgut boundary
M.D., Yokohama City University School of Medicine
Ph.D., Yokohama City University School of Medicine

in vitro, modeling the inter-coordinated specification and invagination of the human hepato-biliary-pancreatic systemfrom human pluripotent stem cells. Coupled with patient-derived stem cells, my group studied the mechanisms ofhuman hepatic diseases that includes viral hepatitis, steatohepatitis, recently extended to drug induced liver injury(DILI), wherein organoid modelled the clinical phenotype and genotype are correlated. Here I will summarize the next

Professional Career
2011 - 20132013 - 2018

Research Associate, Department of Regenerative Medicine, Yokohama City University

2015 - present

Assistant Professor, Division of Gastroenterology, Hepatology and Nutrition and Division of2017 - present

Director of Commercial Innovation, Center for Stem Cell and Organoid Medicine (CuSTOM),

2018 - present

Professor & Founding Director, Communication Design Center, Yokohama City University

2018 - present

Professor, Institute of Research, Tokyo Medical Dental University

and understand drug reactions underlying individual variations in humans.

Associate Professor, Department of Regenerative Medicine, Yokohama City University
Developmental Biology, Cincinnati Children's Hospital Medical Center, USA

References

Cincinnati Children’s Hospital Medical Center, USA

Scientific Activities
2018 - present

Deputy to the Chairman, Japanese Society for Regenerative Medicine (JSRM)

2018 - present

Board of Directors, International Society for Stem Cell Research (ISSCR)

Honors
2020
2018
2016

generation of organoid by design, and discuss its promise and impact to elucidate personalized disease mechanisms

NIH Director’s New Innovator Award, Bethesda, USA
JSPS Prize of The Japan Society for the Promotion of Science, Tokyo
Robertson Investigator Award, New-York Stem Cell Foundation, NY[ 1 ] Koike H, Iwasawa K, Ouchi R , Maezawa M, Giesbrecht K, Saiki N, R-R, Ferguson A, Kimura M , Wendy T, Wells J,
Zorn A, and Takebe T: Modeling human hepato-biliary-pancreatic organogenesis from the foregut-midgut
boundary. Nature, 574(7776):112-116.
[ 2 ] Ouchi R, Togo S, Kimura M, Shinozawa T, Koido M, Koike H, Thompson W, Karns R, Mayhew C, McGrath PS,
McCauley HA, Zhang RR, Lewis K, Hakozaki S, Ferguson A, Saiki N, Yoneyama Y, Takeuchi I, Mabuchi Y, Akazawa C,
Yoshikawa HY, Wells JM, Takebe T*: Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived
Organoids. Cell Metabolism, 30(2):374-384, 2019 (*Correspondence)[ 3 ] Koido M, Kawakami E, Fukumura J, Noguchi Y, Ohori M, Nio Y, Nicoletti P, Aithal G, Daly, A, Watkins P, Anayama
H, Dragan Y, Shinozawa T and Takebe T*. Polygenic architecture informs potential vulnerability to drug-induced
liver injury. Nature Medicine, 2020. (* Correspondence), PMID: 32895570[ 4 ] Shinozawa T , Kimura M , Yuqi C, Saiki N, Yoneyama Y, Ouchi R , Koike H , Koido M, Zhang R-R, Dunn A, Ferguson
A, Togo S, Lewis K, Thompson W, Asai A , Takebe T*: High-Fidelity Drug Induced Liver Injury Screen Using Human
iPSC Liver Organoids. Gastroenterology, in press.

Publications
Koike H, Iwasawa K, Ouchi R , Maezawa M, Giesbrecht K, Saiki N, R-R, Ferguson A, Kimura M , Wendy T, Wells J, Zorn A, and Takebe T: Modeling

1. human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary. Nature, 574(7776):112-116, 2019.
2. Takebe T*, Wells JM *: Organoids-By-Design. Science, 364 (6444), 956-95, 2019. (* Correspondence)
3.
12Camp JG, Sekine K, Gerber T, Loeffler-Wirth H, Binder H, Gac M, Kanton S, Kageyama J, Damm G, Seehofer D, Belicova L, Bickle M, Barsacchi R,
Okuda R, Yoshizawa E, Kimura M, Ayabe H, Taniguchi H, Takebe T*, Treutlein B*: Multilineage communication regulates human liver bud self-organization from pluripotency. Nature, 546, 533–534, 2017. (* Correspondence)

13

Tomoki OGOSHI
Graduate School of Engineering, Kyoto University, Japan
Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Japan

Supramolecular Assemblies of Pillar[n]arenes for
Molecular Separation,
Artificial Water Channels and Biosensor Applications

Contact : ogoshi [at sign] sbchem.kyoto-u.ac.jp
Please replace [at sign] with @.

Tomoki OGOSHI
Graduate School of Engineering, Kyoto University, Japan
Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Japan

Research Interests
Supramolecular Chemistry, Molecular Recognition, Assembly, Organic Chemistry, Polymer Chemistry

size and molecular recognition ability. Numerous supramolecular architectures have been constructed and studied

Education
2000
2002
2005

Macrocyclic compounds play a major role in supramolecular chemistry because of their beautiful shape, nano-scale
as new components of materials as well as entities related to biological structural formation and functions using

B.S. Faculty of Engineering, Kyoto University
M.S. Graduate School of Engineering, Kyoto University
Ph.D. Graduate School of Engineering, Kyoto University (Supervisor: Prof. Yoshiki Chujo)

Professional Career2005 - 2006
2006 - 20102010 - 2015
2015 - 20192019 - present

JSPS Research Fellow (PD): Osaka University (Supervisor: Prof. Akira Harada)

2019 - present

Specially Appointed Professor at Kanazawa University

Assistant Professor at Kanazawa University

various macrocyclic hosts.
In 2008, we reported a new class of macrocyclic hosts named “pillar[n]arenes”.[1,2] They have unique symmetricalpillar structures due to their para-bridge linkage. Based on the pillar-shaped structure, we have produced molecularscale porous materials by assembly of pillar[n]arenes, Due to the pillar-shaped structure, pillar[n]arenes mainly form
one-dimensional (1D) channel structures in crystal state. We discovered that these 1D channel assemblies formed
complexes selectively with high mass fraction of polymers when immersed in polymers with high polydispersity.[3]We have also contacted discrete 1D tubular assemblies using pillar[5]arenes with different rims and applied these
discrete tubes for highly selective artificial water channels.[4] Biosensor applications of functionalized pillar[6]arenes
for quantitative detection of a vitamin metabolite in crude biological samples are also reported.[5]Associate Professor at Kanazawa University
Professor at Kanazawa University
Professor at Kyoto University

Scientific Activities
2013 - 20172018 - present

JST-PRESTO Researcher : JST PRESTO program
JST-CREST Research Investigator

Honors
2019
2016
2016
2014
2013
2012

14

Kao Academic Award
Merck Banyu Lectureship Award / Banyu Chemist Award (MSD Life Science Foundation)
Nozoe Memorial Award for Young Organic Chemists (JPOC)
The Commendation for Science and Technology by the Minister of Education, Culture, Sports,
Science and Technology (MEXT)
Cram Lehn Pedersen Prize in Supramolecular Chemistry (RSC)The Chemical Society of Japan Award for Young Chemists (CSJ)

References

Publications[ 1 ] T. Ogoshi, S. Kanai, S. Fujinami, T. Yamagishi, Y. Nakamoto, Y. J. Am. Chem. Soc. 2008, 130, 5022-5023.

1.
2.

Ogoshi, T.; Kanai, S.; Fujinami, S.; Yamagishi, T.; Nakamoto, Y. J. Am. Chem. Soc. 2008, 130, 5022-5023.

[ 2 ] T. Ogoshi, T. Yamagishi, Y. Nakamoto, Y. Chem. Rev. 2016, 116, 7937–8002.

3.

Ogoshi, T.; Sueto, R.; Yagyu, M.: Kojima, R.: Kakuta, T.: Yamagishi, T.: Doitomi, K.: Tummanapelli, A. K.: Hirao, H.: Sakata, Y.: Akine, S.: Mizuno, M.
Nat. Commun. 2019, 10, 479.

4.
5.
6.
7.

Ogoshi, T.: Maruyama, K.: Sakatsume, Y.: Kakuta, T.: Yamagishi, T.: Ichikawa, T.: Mizuno, M. J. Am. Chem. Soc. 2019, 141, 785-789.

Ogoshi, T.; Yamagishi, T.; Nakamoto, Y. Chem. Rev. 2016, 116, 7937–8002.

Fa, S.; Egami, K.; Adachi, K.; Kato, K.; Ogoshi, T. Angew. Chem. Int. Ed. 2020, 59, 20353–20356.
Fa, S.; Sakata, Y.; Akine, S.; Ogoshi, T. Angew. Chem. Int. Ed. 2020, 59, 9309–9313.
Strilets, D.; Fa, S.; Hardiagon, A.; Baaden, M.; Ogoshi, T.; Barboiu, M. Angew. Chem. Int. Ed. 2020, in press, DOI: 10.1002/anie.202009219.

[ 3 ] Ogoshi, T.; Sueto, R.; Yagyu, M.: Kojima, R.: Kakuta, T.: Yamagishi, T.: Doitomi, K.: Tummanapelli, A.K.: Hirao, H.:
Sakata, Y.: Akine, S.: Mizuno, M. Nat. Commun. 2019, 10, 479.
[ 4 ] Fa, S.; Sakata, Y.; Akine, S.; Ogoshi, T. Angew. Chem. Int. Ed. 2020, 59, 9309–9313; Strilets, D.; Fa, S.;Hardiagon,A.; Baaden, M.; Ogoshi, T.; Barboiu, M. Angew. Chem. Int. Ed. 2020, in press.
[ 5 ] Ueno et al. Revised to Communs. Chem.

15

Toshinori FUJIE

Printed Nanofilm to Engineer Bioelectronic “Second Skin”

School of Life Science and Technology,
Tokyo Institute of Technology, Japan

Toshinori FUJIE
School of Life Science and Technology, Tokyo Institute of Technology, Japan

Contact : t_fujie [at sign] bio.titech.ac.jp
Please replace [at sign] with @.

Integration of flexible electronics into the living system is expected for advancing medical diagnostics and therapeutics.
Such devices should be conformable to the physical and mechanical environment of our body, in which acquired

Research Interests

biosignals should be wirelessly transmitted to external device for health-care management. In this regard, we have

Polymer chemistry, Biomaterial, Printed electronics, Wearable & implantable device, BioRobotics

nanosheet shows tens- to hundreds-of-nanometer thickness close to the scale of biomembranes [1], in which various

envisaged ultra-flexible wearable and implantable devices based on the polymer nanosheet technology. The polymer
types of polymers (e.g., biodegradable polymers, conductive polymers, and elastomers) can be formed into the ultrathin structure by spincoating, layer-by-layer and gravure coating processes. The free-standing nanosheet showed

Education
2009

flexible and adhesive properties derived from ultra-small flexural rigidity (< 10-2 nN m). In this talk, nanosheet-based
Doctor of Engineering, Department of Life Science and Medical Bioscience,
Waseda University

Professional Career2010- 2012

Postdoctoral Research Fellow, Italian Institute of Technology

2012- 2013

Research Associate, Advanced Institute for Materials Research (AIMR), Tohoku University

2013 - 2018

Assistant Professor, Department of Life Science and Medical Bioscience, School of Advanced

2015 - 2019

Researcher, Precursory Research for Embryonic Science and Technology (PRESTO), JST2018 - present

Associate Professor (Lecturer), School of Life Science and Technology, Tokyo Institute ofdevices (namely, printed nanofilms) are introduced by combining nanosheet and printing technologies with variety of
unique inks (Fig. 1) [2]. The printed nanofilm has been utilized as a “second skin” to engineer functional bioelectronicinterface, such as ultra-conformable bioelectrodes for sports science [3] and plant biology [4], and wirelessly-powered,implantable optoelectronics for photodynamic cancer therapy [5].

Science and Engineering / Waseda Institute for Advanced Study, Waseda University

Technology / Leading Initiative for Excellent Young Researchers (LEADER), JSPS

Scientific Activities
2005 - 2015
2015 - present

Construction of polymeric nanosheets and their biomedical application

Fig 1. Printed nanofilms based on nanosheet technology. (Partially reproduced from Ref. 2.)

Integration of nano, bio, electronics for wearable and implantable device

HonorsReferences

2019

Biomaterials Science Emerging Investigators (Royal Society of Chemistry Journal)

2018

The Young Scientists’ Prize for the Commendation for Science and Technology by the Ministerof Education, Culture, Sports, Science and Technology (MEXT), Japan[ 1 ] T. Fujie, Polym. J., 48, 773 (2016).

2017

The Award for Young Investigator of Japanese Society for Biomaterials; Japanese Society for[ 2 ] K. Yamagishi, S. Takeoka, T. Fujie, Biomater. Sci., 7, 520 (2019).

Biomaterials[ 3 ] K. Yamagishi, T. Nakanishi, S. Mihara, M. Azuma, S. Takeoka, K. Kanosue, T. Nagami, T. Fujie, NPG Asia Mater.,
11, 80 (2019).

Publications[ 4 ] H. Taniguchi, K. Akiyama, T. Fujie, B. Chem. Soc. Jpn., 93, 1007 (2020).

1. Suematsu, Y., Tsai, Ya An., Takeoka, S., Franz, C.M., Arai, S. Fujie, T. J. Mater. Chem. B, 8, 6999-7008 (2020).

[ 5 ] K. Yamagishi, I. Kirino, I. Takahashi, H. Amano, S. Takeoka, Y. Morimoto, T. Fujie, Nat. Biomed. Eng., 3, 27 (2019).

2. Yamagishi, K., Nakanishi, T., Mihara, S., Azuma, M., Takeoka, S., Kanosue, K., Nagami, T., Fujie, T. NPG Asia Mater., 11, 80 (2019).
3. Yamagishi, K., Kirino, I., Takahashi, I., Amano, H., Takeoka, S., Morimoto, Y., Fujie, T. Nat. Biomed. Eng., 3, 27-36 (2019).
16

17

Etsuo A. SUSAKI
Department of Systems Pharmacology, Graduate School of
Medicine, The University of Tokyo, Japan

CUBIC-HistoVIsion: a versatile three-dimensional
whole-organ/body staining and imaging based onelectrolyte-gel properties of biological tissue

Contact : suishess-kyu [at sign] umin.ac.jp
Please replace [at sign] with @.

Etsuo A. SUSAKI
Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Japan

Research Interests

T h e re c e n t d e v e l o p m e n t o f v a r i o u s t i s s u e c l e a r i n g a n d t h re e -Multicellular Systems Biology, Aging, Disease model, Tissue clearing, 3D imaging

dimensional (3D) imaging methods, including our CUBIC pipeline [1-2],
allowed the comprehensive observation of the whole organ/body withcellular resolution or more. However, in the long history of histology,
whole-organ/body 3D staining and imaging have been challenging due

Education
2002
2007

to the difficulty of adequate penetration of stains and antibodies. Even
Medical doctor, Faculty of Medicine, Kyushu University
Doctor of Medicine, Graduate School of Medicine, Kyushu University

a small dye occasionally exhibits resistance to penetration, implying acomplex physicochemical environment in the staining system.
In this presentation, we will introduce a versatile whole-organ/bodystaining and imaging protocol named CUBIC-HistoVIsion [3]. To dissect
the complex physicochemical environment, we first conducted a

Professional Career

precise characterization of biological tissue as an electrolyte gel. Then,

2006 - 20102010 - 20132013 - present

by using a simplified tissue-mimicking artificial electrolyte gel. The

Post-doc, Medical Institute of Bioregulation, Kyushu University
Post-doc (JSPS PD/RIKEN SPR), RIKEN CDB
Faculty staff (2019- associate prof.), Graduate School of Medicine, The University of Tokyo

we experimentally evaluated a broad range of 3D staining conditions
combination of essential conditions allowed a bottom-up design ofefficient 3D staining protocol which could uniformly label adult whole
mouse brains, an adult marmoset hemisphere, a ~1 cm3 tissue block ofadult human postmortem cerebellum, and an infant whole marmoset
body with dozens of antibodies and cell-impermeant nucleic acid

Scientific Activities

stains. We also demonstrate that our protocol enabled structural and2002 - 20102010 - present

tracing and whole-brain c-Fos immunostaining. The CUBIC-HistoVIsion

Research on cell cycle/cell activity states and their molecular mechanisms
Development of cell-omics and high-throughput genetics technology

functional neural circuit identification and analysis with Rabies virus
offers advanced opportunities for organ- and organism-scale
histological analysis of multicellular systems in the brain and body.
Fig. 1 Overview of CUBIC-HistoVIsion and representative
3D imaging data of whole mouse brains.

Honors2017
2019

The Young Scientists’ Prize of The Commendation for Science and Technology by the Minister of Education, Culture, Sports, Science and Technology

References

Selected award of PRESTO “Single-cell” area, Japan Science and Technology Agency[ 1 ] Susaki et al. Cell 157: 726-739 (2014)

Publications
1. Susaki EA et al., “Versatile whole-organ/body staining based on electrolyte-gel properties of biological tissues”, Nature Communications 11 (2020) 1982.

[ 2 ] Susaki et al. Nature Protocols 10: 1709-1727 (2015)[ 3 ] Susaki et al. Nature Communications 11: 1982 (2020)

Susaki EA and Ueda HR. “Whole-body and Whole-Organ Clearing and Imaging Techniques with Single-Cell Resolution: Toward Organism-Level

2. Systems Biology in Mammals”, Cell Chemical Biology 23 (2016) 137-157.

3. Susaki EA et al., “Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis”, Cell 157 (2014) 726-739.

18

19

Susumu KITAGAWA
Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Japan
Kyoto University Institute for Advanced Study (KUIAS), JapanNew Dimensions of Porous Coordination Polymers/
Metal-Organic Frameworks

Contact : kitagawa [at sign] icems.kyoto-u.ac.jp

Susumu KITAGAWA

Please replace [at sign] with @.

Institute for Integrated-Cell Material Sciences (WPI-iCeMS), Kyoto University, Japan
Kyoto University Institute for Advanced Study (KUIAS), Japan

Research Interests

The recent advent of porous coordination polymers (PCPs) or metal-organic frameworks (MOFs) as new functional microporous

Coordination Chemistry, Porous Materials, Porous Coordination Polymers (PCPs), Metal-organic Frameworks (MOFs)

creation of unprecedented regular nano-sized spaces and in the finding of novel phenomena [1]. For the sake of consistency, wematerials, have attracted the attention of chemists and physicists due to not only scientific but also application interest in thewill refer to these porous materials as MOFs. Beyond the robust frameworks of MOFs, we discovered the essential attribute of
MOFs that is porous structural flexibility, dissimilar to the conventional porous materials. Porous crystals with soft properties are

Education
1971 - 1974
1975 - 1979

collectively named “soft porous crystal (SPC)”, and flexible MOFs are a class of SPC [2]. Flexible MOFs have a great potential for
Kyoto University, Undergraduate course, Hydrocarbon Chemistry
Kyoto University, Graduate School, Hydrocarbon Chemistry, PhD

gas science & technology [3,4], focusing on energy and environmental, and bio active gases. High-efficiency separation
technology, different from conventional ways, is essential for low-energy separation of gas resources, flue gases, air, pollutant
gases and other industrial materials. Regulation of physiological functions of cells and tissues by spatiotemporally controlled
release of biologically active gases is also important[5]. The future aspects will also be discussed [6,7].

Professional Career2013 - present2017 - present
2020 - present

Director, Institute for Integrated Cell-Material Sciences, Kyoto University
Distinguished Professor (KUIAS)
Deputy Director-General (KUIAS)

Scientific Activities
2013 - 20182013 - 20182012 - 2018

Project Leader of ACCEL, JSPS
Project Leader of Grant-in-Aid for Scientific Research for Specially Promoted Research“Chemistry of Hierarchical Coordination Space”
Project Leader of ACT-C, JSPS “Synthesis of porous coordination-based catalyst for conversion

Figure 1. Different aspects of MOFs obtained from SPCs[7].

of carbon dioxide to methanol”

Honors
2017
2018
2016
2011

Chemistry for the Future Solvay PrizeJapan Academy Prize
The Medal with Purple Ribbon (The Japanese Government)

Publications
1. “Design and control of gas diffusion process in a nanoporous soft crystal”, C.Gu, et al., Science, 2019, 363, 387-391.
2. “Highly responsive nature of porous coordination polymer surfaces imaged by in situ atomic force microscopy”, N.Hosono, et al., Nature Chemistry, 2018, 11, 109-116.
3. “Self-Accelerating CO Sorption in a Soft Nanoporous Crystal”, H.Sato, et al., Science, 2014, 343, 167-170.
“Localized cell stimulation by nitric oxide using a photoactive porous coordination polymer platform”, S.Diring, et al., Nature Commun. 2013, 4,

4. 2684-2691.
20

References

Grand Prix of the Fondation de la Maison de la Chimie[ 1 ] S.Kitagawa, et al., Angew. Chem.Int. Ed., 2004, 43, 2334. Review article[ 2 ] S.Horike, et al., Nature Chem., 2009,1,695. Review article[ 3 ] S.Kitagawa, Angew.Chem.Int.Ed., 2015, 54,10687. Editorial[ 4 ] S.Kitagawa, Acc.Chem.Res., 2017,50,514. Commentary[ 5 ] S.Diring, et al.,Nature Commun., 2013, 4, 2684.
[ 6 ] S.Kitagawa, et al.,Angew. Chem.Int. Ed., 2020, 59, 6652. Review article[ 7 ] S.Kitagawa, et al.,Angew. Chem.Int. Ed., 2020, 59, 15325. Review article

21

Nobuo N. NODA

Autophagy regulation by liquid-liquid
phase separation

Laboratory of Structural Biology
Institute of Microbial Chemistry, Japan
Contact : nn [at sign] bikaken.or.jp

Nobuo N. NODA

Please replace [at sign] with @.

Laboratory of Structural Biology, Institute of Microbial Chemistry, Japan

Autophagy is an intracellular degradation system that involves de novo generation of autophagosomes, which sequester

Research Interests

cytoplasmic materials and deliver them to the lysosome/vacuole for degradation. When autophagy is induced by starvation,

Autophagy, Phase Separation, Structural Biology, In Vitro Reconstitution

generating bulk autophagosomes that randomly sequester cytoplasmic materials. On the other hand, there exist selective types

autophagy-related (Atg) proteins gather to form the pre-autophagosomal structure (PAS), which functions as a place forof autophagy termed “selective autophagy”, during which autophagosome generation proceeds on the specific large cargo that
includes membrane-bound and membraneless organelles. Recently, we noticed that the PAS is a liquid droplet of Atg proteins

Education
2001

that is formed by liquid-liquid phase separation (LLPS) [1]. LLPS of the PAS is strictly regulated by the phosphorylation state of
Ph. D., Graduate School of Pharmaceutical Sciences, The University of Tokyo

Atg13, an intrinsically disordered protein. Upon starvation, Atg13 is dephosphorylated, which links Atg17 dimers to each other toform a large assemblage [2]. In vitro mixing of Atg13 with Atg17 resulted in the formation of liquid droplets, and point mutationsin Atg13 or Atg17 that impaired the droplet formation in vitro also impaired the PAS formation in vivo, suggesting that the PAS isProfessional Career
2001 - 2005
2005 - 2007
2007 - 2011
2011 - 20172017 - present

Postdoctoral Fellow, Hokkaido University

formed by the LLPS of the Atg13-Atg17 complex. High-speed atomic force microscopy observation of the Atg13-Atg17 droplets
revealed randomly arranged, mobile Atg17 molecules inside the droplets, supporting the liquid-like feature of the droplets [1].
Aminopeptidase I (Ape1) is known to be a specific cargo for selective autophagy. We noticed that Ape1 undergoes LLPS to form
Ape1 droplets both in vitro and in vivo [3]. Mutations that impair LLPS or solidify the Ape1 droplets impaired the selective

Research Associate, Hokkaido University

autophagy of Ape1, suggesting that the liquid-like feature of Ape1 droplets is important for selective autophagy. In vitro

Lecturer with Tenure, Hokkaido University

reconstitution experiments revealed that liquid-like Ape1 droplets formed by LLPS, but not Ape1 aggregates that lost theChief Researcher, Institute of Microbial Chemistry

liquidity by a mutation, were selectively sequestered by a membrane coated with Atg proteins. These data suggest that LLPS canbe a general mechanism for regulating both bulk and selective autophagy.

Laboratory Head, Institute of Microbial Chemistry

Scientific Activities
2002 - present
2016 - present

Structural biology of autophagy

References

In vitro reconstitution of autophagy and phase separation[ 1 ] Y. Fujioka, J. M. Alam, D. Noshiro, K. Mouri, T. Ando, Y. Okada, A. I. May, R. L. Knorr, K. Suzuki, Y. Ohsumi, N. N. Noda,“Phase separation organizes the site of autophagosome formation”, Nature, 578 (2020) 301-305.

Honors2012[ 2 ] H. Yamamoto, Y. Fujioka, S. W. Suzuki, D. Noshiro, H. Suzuki, C. Kondo-Kakuta, Y. Kimura, H. Hirano, T. Ando, N.
Young Investigator Award, The Japanese Biochemical Society

N. Noda, Y. Ohsumi, “The intrinsically disordered protein Atg13 mediates supramolecular assembly of autophagy
initiation complexes”, Dev. Cell, 38 (2016) 86-99.
[ 3 ] A. Yamasaki, J. M. Alam, D. Noshiro, E. Hirata, Y. Fujioka, K. Suzuki, Y. Ohsumi, N. N. Noda, “Liquidity is a critical

Publications

determinant for selective autophagy of protein condensates”, Mol. Cell, 77 (2020), 1163-1175.

Y. Fujioka, J. M. Alam, D. Noshiro, K. Mouri, T. Ando, Y. Okada, A. I. May, R. L. Knorr, K. Suzuki, Y. Ohsumi, N. N. Noda, “Phase separation organizes

1. the site of autophagosome formation”, Nature, 578 (2020) 301-305.

A. Yamasaki, J. M. Alam, D. Noshiro, E. Hirata, Y. Fujioka, K. Suzuki, Y. Ohsumi, N. N. Noda, “Liquidity is a critical determinant for selective autophagy of protein

2. condensates”, Mol. Cell, 77 (2020), 1163-1175.

T. Osawa, T. Kotani, T. Kawaoka, E. Hirata, K. Suzuki, H. Nakatogawa, Y. Ohsumi, N. N. Noda, “Atg2 mediates direct lipid transfer between mem-

3. branes for autophagosome formation”, Nat. Struct. Mol. Biol., 26 (2019), 281-288.

22

23

Noriyuki KODERA
Nano Life Science Institute (WPI – NanoLSI),
Kanazawa University

Single-molecule visualization of intrinsically disordered
Rett syndrome protein,
MeCP2 by high-speed Atomic Force Microscopy

Contact : nkodera [at sign] staff.kanazawa-u.ac.jp
Please replace [at sign] with @.

Noriyuki KODERA
Nano Life Science Institute (WPI – NanoLSI), Kanazawa University

Research Interestsbiophysics, molecular motors, cytoskeletons, atomic force microscopy

High-speed atomic force microscopy (HS-AFM) directly visualizes biological molecules in action at nanometerspatial and sub-second temporal resolution. The unique performance of HS-AFM has been demonstrated by direct
observations of many protein systems [1]. Importantly, HS-AFM can even resolve thin and flexible features of
intrinsically disordered regions (IDRs), single polypeptide chains with height of ~0.5 nm, in a protein that could not

Education
2001. Mar
2003. Mar2005. Sep

be analyzed by any techniques at single molecule level. In some cases, dynamic structural transitions in IDRs
B. Sci., Dept. of Phys, Fac. of Sci., Kanazawa Univ.

between ordered- and disordered-conformations can be directly visualized [2-4].
Here, we applied HS-AFM to Methyl-CpG binding protein 2 (MeCP2). MeCP2 is a chromatin regulatory protein

M. Sci., Div. of Math. & Phys. Sci., Grad. Sch. Nat. Sci. & Tech., Kanazawa Univ.

essential for brain development and activity in vertebrates. Specific missense and nonsense mutations in MeCP2

Ph.D., Div. of Basic Sci., Grad. Sch. Nat. Sci. & Tech., Kanazawa Univ.

lead to the neurodevelopmental disorder, Rett syndrome (RTT). HS-AFM demonstrated that MeCP2 transitions
between a fully extended dumbbell-likestructure with the methyl DNA binding domain

Professional Career(MBD) and C-ter minal domain (CTD) at the2005 - 2010

Research Fellow (DC2 & PD), JSPS and Postdoctoral Fellow, CREST, JST

MBD and CTD interact in cis. The MBD within

Assistant Professor & Associate Professor, Bio-AFM Frontier Research Center, Institute of

the full length protein equilibrates between

Science and Engineering, Kanazawa University

unfolded and well folded states. MBD−CTD

2010 - 20182013 - 20172018 - present

PRESTO Researcher, JST
Professor, WPI-NanoLSI, Kanazawa University

extremities, and a compact structure where theinteractions stabilize the MBD in its folded state
and are essential for MeCP2 plasticity (Fig. 1).
The R106W, R133C, F155S and T158M R TT
mutations all showed aberrant MBD dynamics

Scientific Activities
2000 - 2008
2008 - present

Development of high-speed atomic force microscopy (HS-AFM)
Biological application studies using HS-AFM and improvement of HS-AFM

compared to wild type. Further more, we
observed sliding movements of MeCP2 along
dsDNA, bridging two adjacent dsDNAs andDNA condensations by MeCp2. These results
would gain insight into the molecular basis of
RTT [5].

MBD in its folded state.

Honors2017

JSPS Prize

2013

Prize for Science and Technology (Development Category), The Commendation for Science and2012

Young Researcher’s Nanoprobe Technology Prize (JSPS Nanoprobe Technology 167)

Technology by the Minister of Education, Culture, Sports, Science and Technology

Publications
1.

Kodera N, Noshiro D, Dora SK, …, Longhi S, Ando T, “Structural and dynamics analysis of intrinsically disordered proteins by high-speed atomic force
microscopy”, Nat. Nanotech. (in press).

2.

Ngo KX, Kodera N, Katayama E, Ando T, Uyeda TQ, “Cofilin-induced unidirectional cooperative conformational changes in actin filaments revealedby high-speed atomic force microscopy”, eLife 4, 04806 (2015).
Kodera N, Yamamoto D, Ishikawa R, Ando T, “Video imaging of walking myosin V by high-speed atomic force microscopy”, Nature 468, 72-76

3. (2010).
24

Fig.1 HS-AFM images and schematics showing that MBD-CTD interactions stabilize theReferences[ 1 ] T. Ando, Curr. Opin. Chem. Biol., 2019, 51, 105-112.
[ 2 ] M. Hashimoto, N. Kodera, Y. Tsunaka, M. Oda, M. Tanimoto, T. Ando, K. Morikawa, and S. Tate, Biophys. J., 2013,
104, 2222-2234.
[ 3 ] N. Terahara, N. Kodera, T. Uchihashi, T. Ando, K. Namba, and T Minamino, Sci. Adv., 2017, 3, eaao4119.
[ 4 ] N. Kodera, D. Noshiro, SK. Dora, …, S. Longhi, and T. Ando, Nat. Nanotech. (in press).
[ 5 ] N. Kodera, AA. Kalashnikova, …, T. Ando, and JC. Hansen, (in revision).

25

Shinji WATANABE
Nano Life Science Institute (WPI-NanoLSI),
Kanazawa University, Japan

Probing and characterizing nano-bio interfaces byscanning ion conductance microscopy
Shinji WATANABE

Contact : wshinji [at sign] se.kanazawa-u.ac.jp

Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Japan

Please replace [at sign] with @.

Scanning probe techniques with a glass capillary have been widely exploited in the characterization of physical,

Research Interests
Scanning Ion conductance microscopy, Nanoscience, Nanofluidics, Solid-liquid Interfaces,

chemical, and biological properties of nano-bio interfaces. Among these techniques, scanning ion conductancemicroscopy (SICM) has played an essential role in the visualization of live cell surfaces with nanometer-scale resolution.
SICM uses an electrolyte-filled glass pipette as a probe to detect an ion current passing through an aperture of thepipette tip. The ion current variation depending on the distance between the pipette tip and sample surface reflects
various local information of sample surfaces under a liquid environment, such as geometry, surface charge, andmechanical properties of the sample (Fig. 1). However, a longstanding drawback of SICM is an insufficient

Education
2006

spatiotemporal resolution. We have devoted to improve the insufficiency of SICM to realize wide-range applicability ofDoctor of Science, Graduate School Science and Technology, Niigata University

SICM for the investigation of nano-bio interfaces[1-4]. Here we show recent progress of our
improvements and applications using ourProfessional Career

instrument. We developed a tip-scan-type high-2006
2006 - 2007
2007
2007 - 20092009 - 20122012 - 20172017 - 2020
2020 - present

a c t i v e d a m p i n g c o n t ro l m e t h o d t o re d u c e

JST-CREST Postdoctoral Fellow, Niigata University
JST- SORST Postdoctoral Fellow, Niigata University

unwanted vibrations due to the driving of thescanner [2], and the signal enhancement method

Assistant Professor, Department of Physics, Tohoku University

with an ion concentration gradient produced in

Assistant Professor, Center for the Advancement of Higher Education, Tohoku University

the vicinity of the tip [2]. These improvements

JST-ERATO Postdoctoral Fellow, Tohoku University
Assistant Professor, Bio-AFM Frontier Research Center, Kanazawa University
Assistant Professor, Nano Life Science Institute, Kanazawa University

allow us not only to visualize dynamic biologicalprocesses occurring in soft cell surfaces with highroughness but also to map local mechanicalproperties of live cell surface.

Fig. 1: Probing nano-bio interfaces by SICM

Associate Professor, Nano Life Science Institute, Kanazawa University

Scientific Activities
2004 - 20122012 - present

speed SICM scanner with a large stroke [1], an

Spin physics and quantum transport in strongly correlated electron systems.
Instrumentation and applications of scanning ion conductance microscopy.

References[ 1 ] S. Watanabe, and T. Ando, "High-speed XYZ-nanopositioner for scanning ion conductance microscopy" Appl.
Phys. Lett. 111, 113106, (2017).

Publications
1.

K. Shigyou, L. Sun, R. Yajima, S. Takigaura, M. Tajima, H. Furusho, Y. Kikuchi, K. Miyazawa, T. Fukuma, A. Taoka, T. Ando, S. Watanabe, "Geometrical
Characterization of Glass Nanopipettes with Sub-10-nm Pore Diameter by Transmission Electron Microscopy" Anal. Chem. accepted.

2.

S. Watanabe, S. Kitazawa, L. Sun, N. Kodera, and T. Ando, "Development of High-Speed Ion Conductance Microscopy" Rev. Sci. Instrum. 90(12),123704 (2019).
L. Sun, K. Shigyou, T. Ando, and S. Watanabe, "Thermally Driven Approach to Fill Sub-10-nm Pipettes with Batch Production" Anal. Chem. 91,

3. 14080, (2019).

4. S. Watanabe, and T. Ando, "High-speed XYZ-nanopositioner for scanning ion conductance microscopy" Appl. Phys. Lett. 111, 113106, (2017).

26[ 2 ] S. Watanabe, S. Kitazawa, L. Sun, N. Kodera, and T. Ando, "Development of High-Speed Ion Conductance Microscopy" Rev. Sci. Instrum. 90(12), 123704 (2019).
[ 3 ] L. Sun, K. Shigyou, T. Ando, and S. Watanabe, "Thermally Driven Approach to Fill Sub-10-nm Pipettes with Batch
Production" Anal. Chem. 91, 14080, (2019).
[ 4 ] K. Shigyou, L. Sun, R. Yajima, S. Takigaura, M. Tajima, H. Furusho, Y. Kikuchi, K. Miyazawa, T. Fukuma, A. Taoka, T.
Ando, S. Watanabe, "Geometrical Characterization of Glass Nanopipettes with Sub-10-nm Pore Diameter by Transmission Electron Microscopy" Anal. Chem. accepted.

27

Victor SHAHIN
Institute of Physiology II, University of Muenster Medical Faculty,
Germany

Facilitating nuclear delivery of pharmacological
nanoparticles by interfering with the selective
nuclear pore barrier

Contact : shahin [at sign] uni-muenster.dePlease replace [at sign] with @.

Victor SHAHIN
Institute of Physiology II, Medical Faculty of Münster University, Germany

Research Interests
Atomic Force Microscopy, Nanomedicine, Nanotechnology, Physiology, Cancer Physiology

Nuclear pore complexes (NPCs) are elaborate nano-transporters built from diverse proteins termed nucleoporins(Nups). They control all nucleocytoplasmic transport and form a stringent barrier between the cytosol and thenucleus. While selective nucleocytoplasmic transport enables translocation of macromolecules up to striking sizes
approaching megadalton-scale, the upper cutoff for unselective diffusion is at 40 kDa. Elevating the cutoff is of

Education
2002

particular importance for nuclear delivery of therapeutic nanoparticles that are destined to act inside the nucleus.
We study compounds that interfere with the biophysical and functional properties of NPC. The ultimate goal is toDoctor of Pharmacy and Physiology, Pharmacy and Medical Faculties ofraise the upper NPC cutoff for passive nuclear delivery to a substantial degree, relevant for therapeutic

Münster University, Germany

nanoparticles. We present two different classes of compounds that significantly lower the stringency of the NPC
barrier, by two distinct modes of action, interfering with either the NPC channel barrier or the NPC scaffold. Our
ongoing research reveals that former class facilitates nuclear delivery of 5kbp pDNA in up to 10-20% of the tested

Professional Career

cells, compared to no delivery at all in control conditions. We envisage that the various tested compounds of this2002 - 2006

Postdoc, Medical Faculty of Münster/Germany, and University of Cambridge UK

therapeutic nanoparticles.

2006 - 2015

Associate Prof. and group leader, Inst. of Physiology II, Medical Faculty of Münster Univ.

2015 - present

Prof. for Physiology, Inst. of Physiology II, Medical Faculty of Münster Univ.

class may serve as lead substances and usher in the design of potent new strategies to increase nuclear delivery of

Honors2011

Rolf-Dierichs-Stiftung, ‘Innovative Medical Research’ award at the Medical Faculty, Münster

2018

Distinguished lecturer of the year award’ Medical Faculty, Münster

Publications
Liashkovich, I., Rosso, G., Shahin, V., (2019). Nuclear envelope permeability barrier as a fast-response intracellular mechanostat. Advanced Science,

1. 2019 Aug 29;6(21):1900709. doi: 10.1002/advs.201900709.

Azzam, I., Liashkovich, I., Luchtefeld, I., Kouzel IU, Shahin, V., (2019). Facilitating plasmid nuclear delivery be interfering with the selective nuclear

2. pore barrier. Bioeng Transl Med. 2019 Jun 22;4(3):e10136. doi: 10.1002/btm2.10136.

Kramer, A., Liashkovich, I., Oberleithner, H., Ludwig, S., Mazur, I., Shahin, V. 2008. Apoptosis leads to a degradation of vital components of active

3. nuclear transport and a dissociation of the nuclear lamina. PNAS. 105:11236-41.

28

Fig. 1. A: Scheme of the cell nucleus. B: AFM images of the cytoplasmic face of the nuclear
envelope (large image, 4 x 4 μm) and selected NPCs (magnification, bottom right, 280 x 280 nm)
of Xenopus laevis oocytes.From: Shahin,V. (2006). The nuclear barrier is structurally andfunctionally highly responsive to glucocorticoids. BioEssays 28, 935-942.

29

Keehoon JUNG
Department of Anatomy and Cell Biology/Biomedical Sciences, Seoul
National University College of Medicine, Korea

Real-time intravital characterization of non-classicalmonocytes in cancers
Keehoon JUNG

Contact : keehoon.jung [at sign] snu.ac.kr
Please replace [at sign] with @.

Research Interests
Cancer Immunology, In Vivo Imaging, Single-Cell Genomics, Vascular Biology, Drug Development

Department of Anatomy and Cell Biology/Biomedical Sciences
Seoul National University College of Medicine, Korea

Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. However, current anti-VEGF therapies
for CRC provide limited survival benefit as tumors rapidly develop resistance to these agents.
We have developed a miniaturized confocal endomicroscopy technique for spontaneous CRC models in mice. We
recently also established a novel abdominal imaging window. These unique systems enable us to monitor the CRC and
its immune microenvironment longitudinally with a video-rate intravital multi-photon microscope. Using these in vivo
imaging methods and CRC models, we have uncovered an immunosuppressive role for non-classical Ly6Clow

Education
2005
2010

monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated
B.S. in Biological Sciences, KAIST, Korea
Ph.D. in Biological Sciences and Biomedical Science & Engineering Program, KAIST, Korea

in both human and murine tumors following the VEGF signaling blockade, resulting in recruitment of CX3CR1+
Ly6Clow monocytes into the tumor. We also found that treatment with VEGF-A reduced expression of CX3CL1 inendothelial cells. Intravital microscopy revealed that CX3CR1 is critical for Ly6Clow monocyte transmigration across theendothelium in tumors. Moreover, Ly6Clow monocytes recruit Ly6G+ neutrophils via CXCL5 and produce IL-10, which

Professional Career2010 -20132013 -2018
2018- present

Research Fellow at Wellman Center (In Vivo Imaging), Harvard Medical School / MGH
Research Fellow at Steele Laboratories for Tumor Biology, Harvard Medical School / MGH
Assistant Professor, Seoul National University

inhibits adaptive immunity. Preventing Ly6Clow monocyte or Ly6G+ neutrophil
infiltration into tumors enhanced inhibition of tumor growth with anti-VEGFR2
therapy. Further more, we developed a gene therapy using a nanoparticle
formulated with a siRNA against CX3CL1, which reduced Ly6Clow monocyte
recruitment and improved outcome of anti-VEGFR2 therapy in mouse CRCs.
Taken together, we identified immunosuppressive non-classical Ly6Clow monocytes
as key players in tumor resistance to anti-angiogenic therapy in CRCs. We also
revealed molecular mechanisms underlying anti-angiogenic treatment resistance,suggesting potential immunomodulatory strategies to enhance the long-term

Honors20182018 -2027
2017
2016
2016

clinical outcome of anti-VEGF therapies, proven by state-of-the-art in vivo imaging
Milstein Award, International Cytokine & Interferon Society (ICIS)

Fig. 1. Non-classical monocytes flow
through blood vessels as they infiltrate
tumors.

Creative- Pioneering Researchers Program, Seoul National University
Speaker Award, Gordon Research Conference - Angiogenesis
Bristol-Myers Squibb (BMS) Award, Tumor Immunology and Immunotherapy Meeting
AACR-GYRIG Scholar-in-Training Award, AACR Annual Meeting

Publications
1. Choo YW, Jeong J, Jung K. Recent advances in intravital microscopy for investigation of dynamic cellular behavior in vivo. BMB Reports, (2020).
2.

modalities.

Jeong J, Suh Y, Jung K. Context drives diversification of monocytes and neutrophils in orchestrating the tumor microenvironment. Frontiers in
Immunology (2019).
Jung K. et al., Targeting CXCR4-dependent immunosuppressive Ly6C(low) monocytes improves antiangiogenic therapy in colorectal cancer.

3. Proc Natl Acad Sci USA (2017).

4. Jung K. et al., Ly6C(lo) monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy. J Clin Invest (2017).

References[ 1 ] Choo YW, Jeong J, Jung K. Recent advances in intravital microscopy for investigation of dynamic cellular behavior
in vivo. BMB Reports, (2020).
[ 2 ] Jeong J, Suh Y, Jung K. Context drives diversification of monocytes and neutrophils in orchestrating the tumor
microenvironment. Frontiers in Immunology (2019).
[ 3 ] Jung K. et al., Targeting CXCR4-dependent immunosuppressive Ly6C(low) monocytes improves antiangiogenic
therapy in colorectal cancer. Proc Natl Acad Sci USA (2017).
[ 4 ] Jung K. et al., Ly6C(lo) monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy.
J Clin Invest (2017).
[ 5 ] Jung K. et al., Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts. Circ Res (2013).

30

31

Takeshi IMAMURA
Department of Molecular Medicine for Pathogenesis
Ehime University Graduate School of Medicine, Japan

Development of in vivo cancer imaging techniqueby advanced multi-photon laser excitation microscopy
Takeshi IMAMURA

Contact : timamura-ind [at sign] umin.ac.jp
Please replace [at sign] with @.

Research Interests
Bioimaging, Cancer biology, Bone biology, TGF-β signaling

Department of Molecular Medicine for Pathogenesis
Ehime University Graduate School of Medicine, Japan

Recently, heterogeneity is one of the most popular keywords in cancer research. For instance, resistance tochemotherapy has long been thought to be attributed to the heterogeneity of cancer cells. However, it is difficult toprove this using only molecular biology. The easiest approach to answer this question is in vivo fluorescent imaging.
This technique enables the researchers to observe the same cells in living animals for some time. In addition, this allow
us to visualize the molecular activity, cellular function and microenvironment.
Fluorescent imaging technique is a promising technique, and has already been applied for in vitro experiments in

Education

cellular biology. Recently, there has been a growing interest in applying this fluorescent imaging technique to study

1980- 1987

MD. Graduate School of Medicine, Kagoshima University, Kagoshima, JAPAN.

1989- 1993

Ph.D. Graduate School of Medicine, Kagoshima University, Kagoshima, JAPAN.

different disease process and complex biology such as cancer in vivo. Particularly, the in vivo fluorescent imaging using
various fluorophores and/or fluorescent proteins, in conjunction with appropriate microscopy, allows visualization of cell
behavior as well as cell function in vivo.
In this talk, I will talk about applications of the fluorescent imaging systems to monitor cancer cell as well as tumor

Professional Career
1994- 1995

Assistant Professor, Graduate School of Medicine, Kagoshima University. Kagoshima, JAPAN.

1995- 1996

Postdoctoral Fellow, Ludwig Institute for Cancer Research. Uppsala, Sweden.

1996- 2004
2004- 2010

Associate, Associate Member & Group Head, The JFCR Cancer Institute. Tokyo, JAPAN2010 - present

Professor, Ehime University Graduate School of Medicine. Ehime, JAPANDepartment Director, The JFCR Cancer Institute. Tokyo, JAPANmicroenvironment such as angiogenesis in vivo. Using the in vivo fluorescent imaging system, we can visualize not only
cell behavior but also cell function such as cell cycle and epithelial mesenchymal transition (EMT) [1, 2].
Finally, I would like to talk about a technological development of fluorescent imaging methods including two-photon
microscopy and the application of the fluorescent imaging approaches to cancer research. Two-photon microscopy is a
powerful method to investigate behavior and function of cells in deep tissues. Moreover, I would like to present the
setup and application of infrared-(IR)-two-photon microscopy using excitation wavelengths above 1040 nm [3]. IR-twophoton microscopy enables us the application of red fluorescent proteins/dyes and deeper imaging compared withconventional multi-photon microscopy.
In vivo fluorescent imaging technique is now unravelling the cause and result of the heterogeneity among cancer cells
and will pave a way to invent novel approaches for cancer treatment.

Honors
2008“JSBMR Distinguished Scientist Award” by the Society for Bone and Mineral Research

2000“Incitement Award of the Japanese Cancer Association” by the Japanese Cancer Association

Publications
1. Inoue M et al. Rational Engineering of XCaMPs, a Multicolor GECI Suite for In Vivo Imaging of Complex Brain Circuit Dynamics. Cell. 177: 1346-60, 2019.
Yoon JH et al. Phosphorylation status determines the opposing functions of Smad2/Smad3 as STAT3 cofactors in TH17 differentiation. Nat

2. Commun. 6: 7600, 2015

3. Sakaue-Sawano A, et al., Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell. 132: 487-98, 2008.

References[ 1 ] Sakaue-Sawano A, et al., Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell. 132:487-98, 2008.
[ 2 ] Ieda T et al., Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment-colorectal
cancer network. Sci Rep. 9: 16378, 2019.

[ 3 ] Grzybowski M et al., A highly photostable near-infrared labeling agent based on a phospharhodamine for longterm and deep imaging. Angew Chem Int Ed Engl. 57: 10137-10141, 2018.

4. Yoshida Y et al. Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell. 103: 1085-97, 2000.
5. Lu SL et al. HNPCC associated with germline mutation in the TGF-βtype II receptor gene. Nat Genet. 19: 17-8, 1998.
6. Imamura T et al. Smad6 inhibits signalling by the TGF-β superfamily. Nature. 389: 622-6, 1997.

32

33

Ann-Marie CHACKO
Assistant Professor, Cancer & Stem Cell Biology Programme,
Head, Laboratory for Translational and Molecular Imaging (LTMI)
Duke-NUS Medical School, Singapore
Contact : ann-marie.chacko [at sign] duke-nus.edu.sg
Please replace [at sign] with @.

Developing novel probes for in vivo molecular
PET imaging of cancer immunotherapy
Ann-Marie Chacko
Cancer and Stem Cell Biology Programme, Laboratory for Translational and Molecular Imaging, Duke-NUS Medical School, Singapore

Nuclear imaging technologies, such as positron emission tomography (PET), offers the potential to noninvasively

Research Interests

visualise and quantify biomarkers at a cellular level as they occur in their native environment, and in real time. PET of

Molecular Imaging, In Vivo Diagnostics, Drug Delivery Systems, Cancer Immunotherapy, Clinical Translation

Immunotherapy (CI), as it could provide a pivotal platform for validating treatment safety and efficacy for the number of

the tumour immune microenvironment (TME) is a fairly nascent field of study, and is highly relevant in the era of Cancer
CI combinations that are poised or already in clinical testing.
In this talk, I will outline our strategies to identify and validate prognostic and predictive biomarkers aimed to ultimately

Education

improve CI outcome. Specifically, I will highlight our preclinical efforts to track endogenous immune cell markers of
metabolism and inflammation (18F-FDG-PET), proliferation (18F-FLT-PET), and cytotoxic T cell activity (18F-GZB-PET).

2001

B.Sc. Honours Biochemistry, Bishop’s University, Sherbrooke, QC, Canada

2003

M.Sc. Chemistry, University of Western Ontario, London, ON, Canada

2008

Ph.D. Pharmacological Sciences, University of Pennsylvania, Philadelphia (UPenn), PA, USA

We will also discuss strategies of taking probes beyond the preclinical space, towards the clinic. “Shedding light” on
immune response and their modulation, will have important implications for assessing treatment response during
therapeutic intervention trials in cancer, and in other immune-related diseases including emerging infectious disease.

Professional Career
2008- 2010

Postdoctoral Fellow, Pharmacology and Program in Targeted Therapeutics, Institute of Transla-

2011- 2012

Postdoctoral Fellow, Division of Clinical Molecular Imaging and Nuclear Medicine, Department

2012- 2014

KL2 Fellow, Clinical and Translational Sciences, ITMAT, UPenn, Philadelphia, PA, USA

2012- 2014

Research Associate, Division of Clinical Molecular Imaging and Nuclear Medicine, Department

2015 - present

Assistant Professor, Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School,tional Medicine and Therapeutics (ITMAT), UPenn, Philadelphia, PA, USA

of Radiology, UPenn, Philadelphia, PA, USA

of Radiology, UPenn, Philadelphia, PA, USA

Singapore

Publications
Goggi JL, Hartimath SV, Hwang YY, Tan YX, Khanapur S, Boominathan R, Jiang L, Husaini AR, Cheng P, Yong FF Tan PW, Yuen TY, Jieu B, Chacko AM,

1. Larbi A, Renia L, Johannes C, Robins, EG. Examining Immunotherapy Response Using Multiple Radiotracers. Mol. Imaging Biol. Mol. Imaging Biol. 2020;22(4):993-1002.

Herr K, Serrano RMF, Ong J, Madan B, Virshup DM, Chacko AM. Characterization of anti-Frizzled Antibody [Zr-89] 18R5 for PET Imaging of Pancreat-

2. ic Cancer. J Nucl Med. 2016, 57(2):58

Chacko AM, Han JY, Greineder CF, Zern BJ, Mikitsh JL, Nayak M, Menon D, Johnston IH, Poncz M, Eckmann DM, Davies PF and Muzykantov VR.

3. Enhancement of nanocarrier targeting to vascular endothelium via collaborative epitope engagement. ACS Nano. Jul 2015. 9(7):6785-93.

3435

Masanobu OSHIMA

Polyclonal metastasis of colorectal cancer

Nano Life Science Institute (WPI-NanoLSI),
Cancer Research Institute, Kanazawa University, Japan

Masanobu OSHIMA
Nano Life Science Institute (WPI-NanoLSI), Cancer Research InstituteKanazawa University, Japan

Contact : oshimam [at sign] staff.kanazawa-u.ac.jp
Please replace [at sign] with @.

Colorectal cancer (CRC) is a leading cause of cancer-related death globally, and the majority of cancer-related deaths
are caused by metastasis. It is therefore important to predict metastatic ability of the primary cancers to establish a

Research Interests
Mouse genetics, organoid, microscopy imaging, microenvironment, metastasis

colorectal cancer, and comprehensive genome research has identified driver genes that are frequently mutated in CRC.
Using genetic mouse models, we have constructed mouse models and established intestinal tumor-derived organoids
carrying various combinations of driver mutations, Apc (A), Kras (K), Tgfbr2 (T), Trp53 (P), and Fbxw7 (F).
Comprehensive phenotype analyses revealed that AT and AP mutation combinations cause submucosal invasion, AKT

Education
1982 - 1986
1986 - 1988

clinical strategy. The accumulation of driver mutations is responsible for development and malignant progression ofand AKP combinations induce advanced malignant phenotype like epithelial-mesenchymal transition (EMT), and AKTP
Faculty of Veterinary Medicine, Hokkaido University
Hokkaido University Graduate School of Veterinary Medicine (MS)and AKTPF acquire highly metastatic ability from the spleen to liver [1-3], which is consistent with the establishedconcept of multistep tumorigenesis based on Darwin evolution. However, a unique concept for metastasis, polyclonal
metastasis, has recently been proposed. We therefore examined the mechanism of polyclonal metastasis by labeled
the intestinal tumor-derived organoids with Venus and tdTomato. When non-metastatic (Non-M) cells are transplanted

Professional Career

into the spleen with malignant metastatic (MM) cells, they

1988 - 1991

Staff Scientist, Chugai Pharmaceutical Co. Ltd.

cells, but not Non-M cells, induce niche generation

1992 - 1997

Staff Scientist, Banyu Tsukuba Research Institute (Merck)

1997 - 1999
2000 - 2005

Research Associate, Merck Research Laboratories, USA

expressing cells promotes the colonization of Non-M cells.

Associate Professor, Kyoto University Graduate School of Medicine

metastasize via the polyclonal mechanism using the2005 - present2017 - present

Professor, Cancer Research Institute, Kanazawa University

microenvironment that is generated by malignant cells.

form chimeric metastatic foci in the liver. Importantly, MMsurrounding disseminated tumor clusters, and suchmicroenvironment consisting of macrophages and αSMAT h e s e re s u l t s i n d i c a t e t h a t n o n - m e t a s t a t i c c e l l s c a n

Professor, Nano Life Science Institute (WPI-NanoLSI), Kanazawa University

AKTP organoids

AKTP and AP chimeric spheroids
for spleen transplantation

Scientific Activities
1992 - 2005

Mouse genetics studies for chemoprevention of intestinal tumorigenesis

2005 - present

Mouse genetics and organoid research for gastrointestinal cancer malignant progression

References[ 1 ] Oshima H, Nakayama M, Han TS, Naoi K, Ju X, Maeda Y, Robine S, Tsuchiya K, Sato T, Taketo MM, and Oshima M.

Honors
2012
2013
2015
2020

Suppressing TGF-β signaling in regenerating epithelia in an inflammatory microenvironment is sufficient to cause
invasive intestinal cancer. Cancer Res, 75: 754-765, 2015.
JCA-Mauverynay Award, Japanese Cancer Association
Achievement Commendation of Kanazawa University, Kanazawa University
The Commendation for Science and Technology, MEXT
Ishikawa Television Award, Ishikawa TV Broadcasting Co. Ltd

Publications[ 2 ] Nakayama M, Sakai E, Echizen K, Yamada Y, Oshima H, Han TS, Ohki R, Fujii F, Ochiai A, Robine S, Voon DC,
Tanaka T, Taketo MM, and Oshima M. Intestinal cancer progression by mutant p53 through the acquisition ofinvasiveness associated with complex glandular formation. Oncogene, 36: 5885-5896, 2017.
[ 3 ] Sakai E, Nakayama M, Oshima H, Kouyama Y, Niida A, Fujii S, Ochiai A, Nakayama KI, Mimori K, Suzuki Y, Hong CP,
Ock CY, Kim SJ, and Oshima M. Combined mutation of Apc, Kras and Tgfbr2 effectively drives metastasis of intestinal cancer. Cancer Res, 78: 1334-1346, 2018.

Nakayama M, Hong CP, Oshima H, Sakai E, Kim SJ, and Oshima M. Loss of wild-type p53 promotes mutant p53-driven metastasis through acquisition

1. of survival and tumor-initiating properties. Nat Commun, 11: 2333. 2020.

Takeda H, Kataoka S, Nakayama M, Ali MAE, Oshima H, Yamamoto D, Park JW, Takegami Y, An T, Jenkins NA, Copeland NG, and Oshima M.

2. CRISPR-Cas9 mediated gene knockout in intestinal tumor organoids provides functional validation for colorectal cancer driver genes. Proc Natl Acad
Sci USA, 116: 15635-15644, 2019.

Oshima H, Kok SY, Nakayama M, Murakami K, Voon DC, Kimura T, and Oshima M. Stat3 is indispensable for damage-induced crypt regeneration but

3. not for Wnt-driven intestinal tumorigenesis. FASEB J, 2019.
36

37

Memo