Mako KAMIYA

Chemical Biology

Under Moonshot Goal 7, “Brain Senoinflammation,” we are leading a subproject entitled “Development of Optical Probes toward the Realization of Dementia-Free Society.”

To elucidate how cells that play critical roles in the formation of brain senoinflammation such as senescent cells and inflammatory cells affect other organs, it is essential to establish technologies that enable selective visualization of these cells in vivo, as well as techniques to perturb their functions. In this subproject, we aim to develop optical probes whose optical properties change in response to molecules or activities characteristic of these cells, thereby enabling selective imaging of these cells. In addition, we seek to create novel photo-functional molecules that can induce selective perturbations to these cells and to establish technical platforms for analyzing the dynamics of factors released from these cells and their effects on other organs. Like this, we aim to contribute to the realization of dementia prevention and treatment through the development of novel optical imaging methods.

We have previously established original molecular design strategies to develop a variety of novel photo-functional small molecules. Based on these knowledge, we aims to further advance our molecular design strategies to create a diverse array of optical probes that will contribute to the understanding of the mechanisms underlying dementia.

Development of Optical Probes for Detecting Brain Senoinflammatory-related Cells

We aim at developing optical probes for selective visualization of cells that play critical roles in the formation of senoinflammation in the brain, including senescent cells and inflammatory cells. First, we identify molecules and activities characteristic of these cells and develop optical probes whose optical properties change upon detecting these targets. In addition, we are working to establish novel molecular design strategies for fluorescent probes with superior capability of intracellular retention that exhibit low cell cytotoxicity, with the aim of creating optical imaging probes that enable the selective observation of target cells in vivo.

Development of Photo-Functional Molecules for Perturbing Specific Cell Types

To establish technologies that enable spatiotemporally controlled perturbation of specific cell types among the diverse cell populations present in the brain, we are advancing the functionalization of conventional caged compounds and photosensitizers. Specifically, we are developing photo-functional molecules that undergo uncaging reactions to release drugs or bioactive molecules only under long-wavelength light and specific conditions, as well as molecules that exhibit photosensitizing activity in response to light irradiation exclusively in specific cell types. Through the establishment of these technologies, we aim to create perturbation methods that allow selective manipulation of the functions of specific cells and to elucidate how these cells influence other organs.

Okinaka M, Kawatani M, Fujioka H, Spratt S, Ito H, Misawa Y, Otake R, Ishikawa A, Kojima R, Urano Y, Ozeki Y,  Kamiya M*: Functional Raman probes for detecting enzyme activities based on aggregation control.  Anal. Chem. 97, 19057–19065 (2025). Doi: 10.1021/acs.analchem.5c02231

Kuriki Y, Sogawa M, Komatsu T, Kawatani M, Fujioka H, Fujita K, Ueno T, Hanaoka K, Kojima R, Hino R, Ueo H, Ueo H, Kamiya M*, Urano Y*: Modular Design Platform for Activatable Fluorescence Probes Targeting Carboxypeptidases Based on ProTide Chemistry. J. Am. Chem. Soc. 146, 521–531 (2024). Doi: 10.1021/jacs.3c10086

Fujioka H, Kawatani M, Spratt S, Komazawa A, Misawa Y, Shou J, Mizuguchi T, Kosakamoto H, Kojima R, Urano Y, Obata F, Ozeki Y, Kamiya M*: Activatable Raman probes utilizing enzyme-induced aggregate formation for selective ex vivo imaging. J. Am. Chem. Soc. 145, 8871–8881 (2023). Doi: 10.1021/jacs.2c12381

Kuriki Y, Yoshioka T, Kamiya M*, Komatsu T, Takamaru H, Fujita K, Iwaki H, Nanjo A, Akagi Y, Takeshita K, Hino H, Hino R, Kojima R, Ueno T, Hanaoka K, Abe S, Saito Y, Nakajima J, Urano Y*: Development of a fluorescent probe library enabling efficient screening of tumour-Imaging probes based on discovery of biomarker enzymatic activities. Chem. Sci. 13, 4474-4481 (2022). Doi: 10.1039/D1SC06889J

Obara R, Kamiya M*, Tanaka Y, Abe A, Kojima R, Kawaguchi T, Sugawara M, Takahashi A, Noda T, Urano Y*: γ-Glutamyltranspeptidase (GGT)-Activatable Fluorescence Probe for Durable Tumor Imaging. Angew. Chem. Int. Ed. 60, 2125-2129 (2021). Doi: 10.1002/anie.202013265