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1. 細胞の生存増殖と細胞死シグナルの研究


2. 内分泌細胞のホルモン分泌顆粒の形成、維持、放出機構の研究

3. 低分子プローブを利用した細胞機能および疾患病態の解析

Specific aims:

To elucidate formation mechanisms for highly integrated functions of differentiated cells such as pancreatic β-cells and neuronal cells with use of molecular and cellular technical approaches.

Projects (~2016):

1. Mechanisms on peptide hormones secretion and secretory granule formation in endocrine cells.
Peptide hormones synthesized at the endoplasmic reticulum are transported to the trans-Golgi network (TGN) where they are sorted and specifically targeted to secretory granules in neuroendocrine cells. We found that secretory granule protein, phogrin, binds to CPE and clathrin adaptors through the luminal region and the cytoplasmic tail, respectively, suggesting that this transmembrane protein has a role in hormone sorting by providing a communication device between the granule lumen and the cytosol. We further investigate the regulatory secretion and degradation of peptide hormones using a recently developed multi-tag imaging system.

2. Mechanisms on growth, survival, and cell death in pancreatic β-cells and neuronal cells.

We have discovered that phogrin functions as a regulatory mediator bridging between glucose/insulin secretion and autocrine insulin signaling in the growth of pancreatic β-cells. We are analyzing its physiological role with use of the gene-targeted mouse. In addition, we investigate the signaling pathway of novel necrotic cell death such as necroptosis and ferroptosis with tumor cells or neuronal cells.

3. Development of fluorescent or luminescent probes for investigating various diseases.
In a collaborative study with some engineering groups, we are developing fluorescent or luminescent probes to dissect molecular mechanisms of dysfunction in cancer, diabetes, and other diseases. We demonstrated previously that reactive oxygen species are localized at autophagosomes/lysosomes in a basal state and they are eventually implicated to neuronal cell death by cerebral ischemia.