Chemical Imaging Techniques

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Chemical biology is an interdisciplinary research field, which focuses on elucidation of biological phenomena by utilizing "chemical tools". These chemical tools are developed by the combinatorial use of organic chemistry, nanotechnology, and genetic engineering. In our group, we design and synthesize chemical tools that are applied to answer various biological questions. We are currently developing fluorescent probes for live-cell imaging and magnetic resonance imaging (MRI) probes for in-vivo applications. One of our major projects related to fluorescence is the development of protein labeling methods using new protein tags and fluorescent probes (Figure 1). Other fluorescence-related projects are detection of pH change and enzymatic activity using fluorescent probes. By using these probes, we verified the translocation of glucose transporter, histone deacetylase activity, and osteoclast activity. While fluorescent probes are powerful tools for detecting cellular events, MRI probes are advantageous in visualizing biological phenomena in living animals. We developed nanoparticle probes for imaging cancer and inflammation using MRI techniques (Figure 2). These chemical tools give new findings that are not verified by conventional biological methods. By using these tools, we are currently studying various biological fields such as epigenetics, immunology, and cancer biology.

Figure 1. Fluorescent probes for live-cell imaging of proteins.

Figure 2. MRI probe for in vivo imaging.

Principal Investigator

Kazuya Kikuchi Principal Investigator

Research field: Design and synthesis of sensor molecules for visualizing biological events in living cells and in vivo
kkikuchi atmark
Education history
1984 B.S. The University of Tokyo (Bioorganic Chemistry)
1994 Ph.D. The University of Tokyo (Bioorganic Chemistry)
1994-1995 Postdoctoral University of California, San Diego (Pharmacology)
1995-1996 Postdoctoral The Scripps Research Institute (Biochemistry)
Research and career history
1994-1995 Postdoctoral Research Associate with Prof. Roger Y. Tsien University of California, San Diego, Department of Pharmacology
1995-1996 Postdoctoral Research Associate with Prof. Donald Hilvert The Scripps Research Institute, Department of Chemistry and Molecular Biology
1997-2000 Assistant Professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo
2000-2005 Associate Professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo
2005- Professor, Graduate School of Engineering, Osaka University


Yuichiro Hori Associate Professor
horiy atmark
Yuriko Miyata Secretary
ymiyata atmark


H. Maeda, T. Kowada, J. Kikuta, M. Furuya, M. Shirazaki, S. Mizukami, M. Ishii, & K. Kikuchi, ''Real-time intravital imaging of pH variation associated with osteoclast activity'', Nat. Chem. Biol., 12, 579-585 (2016)
S. Hirayama, Y. Hori, Z. Benedek, T. Suzuki, & K. Kikuchi, ''Fluorogenic probes reveal a role of GLUT4 N-glycosylation in intracellular trafficking'', Nat. Chem. Biol., 12, 853-859 (2016)
Y. Hori, S. Hirayama, M. Sato, & K. Kikuchi, ''Redesign of a Fluorogenic Labeling System to Improve Surface Charge, Brightness, and Binding Kinetics for Imaging the Functional Localization of Bromodomains'', Angew. Chem. Int. Ed., 54, 14368-14371 (2015)
T. Nakamura, H. Matsushita, F. Sugihara, Y. Yoshioka, S. Mizukami, & K. Kikuchi, ''Activatable 19F MRI Nanoparticle Probes for the Detection of Reducing Environments'', Angew. Chem. Int. Ed., 54, 1007-1010 (2015)
Z. Zeng, S. Mizukami, K. Fujita, & K. Kikuchi, ''An Enzyme-Responsive Metal-Enhanced Near-Infrared Fluorescence Sensor Based on Functionalized Gold Nanoparticles'', Chem. Sci., 6, 4934-4939 (2015)
T. Nakamura, F. Sugihara, H. Matsushita, Y. Yoshioka, S. Mizukami, & K. Kikuchi, ''Mesoporous Silica Nanoparticles for 19F Magnetic Resonance Imaging, Fluorescence Imaging, and Drug Delivery'', Chem. Sci., 6, 1986-1990 (2015)
H. Matsushita, S. Mizukami, F. Sugihara, Y. Nakanishi, Y. Yoshioka & K. Kikuchi, “Multifunctional Core-shell Silica Nanoparticles for Highly Sensitive 19F MRI”, Angew. Chem. Int. Ed., 53, 1008-1011 (2014).
S. Okada, S. Mizukami, T. Sakata, Y. Matsumura, Y. Yoshioka, and K. Kikuchi, ''Ratiometric MRI Sensors Based on Core-Shell Nanoparticles for Quantitative pH Imaging'', Adv. Mater., 26, 2989-2992 (2014)
Y. Hori, T. Norinobu, M. Sato, K. Arita, S. Shirakawa & K. Kikuchi, “Development of Fluorogenic Probes for Quick No-Wash Live-Cell Imaging of Intracellular Proteins”, J. Am. Chem. Soc., 135, 12360–12365 (2013).
Y. Hori, K. Nakaki, M. Sato, S. Mizukami & K. Kikuchi, “Development of Protein Labeling Probes with Redesigned Fluorogenic Switch Based on Intramolecular Association and No-wash Live-cell Imaging”, Angew. Chem. Int. Ed., 51, 5611-5614 (2012).
S. Mizukami, S. Watanabe, Y. Akimoto & K. Kikuchi, “No-Wash Protein Labeling with Designed Fluorogenic Probes and Application to Real-Time Pulse-Chase Analysis”, J. Am. Chem. Soc., 134, 1623-1629 (2012).
R. Baba, Y. Hori, S. Mizukami & *K. Kikuchi, “Development of Fluorogenic Probe with Transesterification Switch for Detection of Histone Deacetylase Activity”, J. Am. Chem. Soc., 134, 14310-14313 (2012).
T. Kowada, J. Kikuta, A. Kubo, M. Ishii, H. Maeda, S. Mizukami & K. Kikuchi, “In Vivo Fluorescence Imaging of Bone-Resorbing Osteoclasts”, J. Am. Chem. Soc., 133, 17772-17776 (2011)
S. Mizukami, T. Yamamoto, A. Yoshimura, S. Watanabe & K. Kikuchi, “Covalent Protein Labeling with a Lanthanide Complex and its Application to Photoluminescence Lifetime-based Multicolor Bioimaging”, Angew. Chem. Int. Ed., 50, 8750-8752 (2011).
S. Mizukami, M. Hosoda, T. Satake, S. Okada, Y. Hori, T. Furuta & K. Kikuchi, “Photocontrolled Compound Release System Using Caged Antimicrobial Peptide”, J. Am. Chem. Soc., 132, 9524-9525 (2010).
S. Mizukami, R. Takikawa, F. Sugihara, M. Shirakawa & K. Kikuchi, “Dual Functional Probe to Detect Protease Activity for Fluorescence Measurement and 19F MRI”, Angew. Chem. Int. Ed., 48, 3641-3643 (2009).
Y. Hori, H. Ueno, S. Mizukami & K. Kikuchi, “Photoactive Yellow Protein-Based Protein Labeling System with Turn-on Fluorescence Intensity”, J. Am. Chem. Soc., 131, 16610-16611 (2009).
S. Mizukami, S. Watanabe, Y. Hori & K. Kikuchi, “Covalent Protein Labeling Based on Non-catalytic -Lactamase and a Designed FRET Substrate”, J. Am. Chem. Soc., 131, 5016-5017 (2009)
S. Mizukami, R. Takikawa, F. Sugihara, Y. Hori, H. Tochio, M. Wälchli, M. Shirakawa & K. Kikuchi, “Paramagnetic Relaxation-based 19F MRI Probe to Detect Protease Activity”, J. Am. Chem. Soc., 130, 794-795 (2008).
S. Mizukami, K. Tonai, M. Kaneko & K. Kikuchi, “Lanthanide-based Protease Activity Sensors for Time-resolved Fluorescence Measurements”, J. Am. Chem. Soc., 130, 14376-14377 (2008).

Awards and Honors

2008 IBM Science Award
2008 Emerging Investigator Award, Royal Society of Chemistry, UK
2004 Young Investigator Award, Japanese Society of Bio-imaging
2002 Young Investigator Award, Japanese Pharmaceutical Society