Research

Theme 1

Mechanism and significance of hormone secretion

Various hormones in our body play important roles in our physiological functions. For example,

Insulin: secreted from the pancreas, decreases blood glucose levels.

Growth hormone: secreted from the brain, enhances physical growth.

Estrogen, progesterone (female hormones): secreted from the ovary, forms sexual characteristics and estrus cycles.
Androgen (male hormone): secreted from the testis, forms sexual characteristics and hair growth.

Among a variety of hormones, I particularly investigate gut hormones, secreted from the gastrointestinal tract. The gastrointestinal tract is widely known to digest food to take up nutrients, but also secretes hormones many of which are involved in the regulation of appetite.

Recent studies have also revealed close interaction between gut hormone secretion and gut microbiota, and microbiota-derived metabolites. This fact demonstrates the importance of gut hormones as an interface connecting intestinal environment and whole-body functions.

I have been engaged in understanding the molecular mechanisms underlying gut hormone secretion in the enteroendocrine cells since the graduate school student period. I mainly utilize live-cell imaging techniques with fluorescence microscopy which enable real-time observation of specific proteins. In particular, total internal reflection fluorescence (TIRF) microscopy can specifically visualize the fluorescence near the plasma membrane and is suitable for observing secretory vesicles, cytoskeleton, and membrane-localized proteins.

Using these techniques, I have investigated the mechanisms of secretion of glucagon-like peptide-1 (GLP-1) and published several articles (Harada et al., Biochem Biophys Res Commun, 2015; Harada et al., J Biol Chem, 2017; Nakamura et al., J Mol Endocrinol, 2020; Harada et al., FEBS Lett, 2023, etc.).

TIRF microscopy movies of secretory vesicles (left, from Harada et al., Biochem Biophys Res Commun, 2015), actin cytoskeleton, and ion channels (middle and right, respectively, both from Harada et al., J Biol Chem, 2017) in an enteroendocrine cell line.

In addition, I perform histological analysis, RNA-sequencing, metagenome, and metabolome analysis to clarify the physiological significance of gut hormone secretion using animal models including KO mice (Harada et al., Mol Metab, 2025). I am trying to understand the functional relationship between multiple cells and organs and ultimately the overall role of gut hormones in the body.

Theme 2

Development of fluorescent protein-based indicators visualizing intracellular molecular dynamics

When a drastic action takes place in the cells including hormone secretion, level of specific intracellular molecules (i.e. second messengers) changes and provokes responses of various proteins which regulate cellular functions. Researchers have developed techniques to clarify the timing, scale, and speed of changes in the level of these second messengers. One of the representative tools is the genetically encoded protein indicators based on fluorescent proteins derived from jellyfish and corals. These fluorescent protein-based indicators can visualize changes in the level of specific intracellular molecules as changes in fluorescence intensity, and we can monitor the dynamics of intracellular molecules using fluorescence microscopy. I have joined many projects developing the novel indicator proteins which can visualize cAMP, cGMP, and energy metabolism-related molecules such as ATP, glucose, lactate, and pyruvate (Matusda et al., ACS Sens, 2017; Harada et al., Sci Rep, 2017; Harada et al., Sci Rep, 2020; Mita et al., Cell Chem Biol, 2022, etc.).

Movies of the cells expressing the green cGMP indicator Green cGull (left, from Matsuda et al., ACS Sens, 2017) and the red cAMP indicator Pink Flamindo (right, from Harada et al., Sci Rep, 2017).

Theme 3

Effect of environmental chemicals on the health

Based on my research experiences, I am currently aiming at contribution to the field of environmental and health science in the current affiliation, National Institute for Environmental Studies in Japan.

Various chemical substances are released into the environment by human activity. Some of the chemicals are reported to cause adverse effects on human health and the ecosystem, and people have defined regulations of standard concentrations in the atmosphere, water, and food ingredients. I am mainly focusing at plastic waste, and investigating the biodistribution in animals and cytotoxicity of nanoplastic particles.

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