Yokohama City University

Principal Investigator_S.Ohno

Identification of the physiological and pathological significance of post-translational modification

Shigeo Ohno
Professor, Molecular Biology
researchmap

Our Aim

Recent studies have revealed the mechanism of tissue maintenance. Here, we extend these studies to establish a rationale for the development of disease-specific biomarkers and the finding of drug targets.

Background

A variety of diseases are caused by defects in tissue maintenance. However, the molecular mechanism regulating tissue maintenance remains unclear. Recent studies have revealed the pivotal importance of the mechanism regulating cell polarity in a variety of physiological and pathological contexts, indicating the importance of polarityrelated proteins and their post-translational modifications (PTM) as potential diagnostic markers and drug targets.

Research Overview

We will analyze the changes in PTM during the establishment and maintenance of tissues with the aid of a variety of model systems and clinical samples. More specifically, we will focus on the signaling pathways that regulate cell polarity and cell fates and have extended our studies to diseases such as cancer and renal diseases to identify critical proteins and their PTMs. Such approaches will provide us with not only essential information required for the understanding of the mechanism of the development of diseases, but also candidates for disease-specific biomarkers and drug targets.

Achievements

We have revealed the importance of the aPKC-PAR system that regulates cell polarity in the maintenance of a variety of tissues and organs. Further, we have revealed the aPKCIL6 axis that is involved in the development of a variety of cancers. We have also revealed a novel aPKC-ErbB2 axis that is involved in the maintenance of mammary tissues and mammary cancer stem cells. As for the maintenance of the glomerulus, we have revealed the importance of the exocytosis of nephrin, a major slit diaphragm protein, and the involvement of aPKC in the maintenance of the slit diaphragm.