Specialized field
Functional biochemistry, cell biology, developmental biology, general medical chemistry, glycobiology, stem cell biology, biochemistry, molecular biology
Research theme
We are conducting research with the aim of clarifying the role of glycans in living organisms. We use various genetic engineering techniques to regulate the expression of glycan-related genes in Drosophila individuals, ES cells, iPS cells, cancer cells, cancer stem cells, human model cells, and organoids to clarify glycan functions. We also create knockout mice for some genes and conduct analysis.
(1) Analysis of glycan-related genes in Drosophila; elucidation of physiological functions of glycans conserved across species
Drosophila is the most advanced model animal in genetics. We focus on the "physiological activity of glycans conserved across biological species" and elucidate the role of glycans in the development of organisms through phenotypic analysis of mutants and knockdowns of glycan-related genes in Drosophila, as well as biochemical and molecular biological analysis. In particular, we are currently analyzing glycosyltransferases required for the maintenance and differentiation of blood stem cells, and glycan structures required for the formation of nerve axons.
(2) Elucidation of glycan functions in human and mammalian pluripotent stem cells (ES cells, iPS cells) and organoids
(1) We will use cultured cells, mainly embryonic stem cells, to examine whether the glycan functions revealed in the previous study are common to humans and other mammals. Specifically, we aim to "elucidate the role of glycans in stem cell maintenance and differentiation" by targeting ES cells and iPS cells. In this project, we first revealed in 2008 that glycans (heparan sulfate) are involved in the maintenance of ES cells. We have further developed this to reveal that the four glycan structures mentioned above are necessary for maintaining the naive pluripotent state. We are currently expanding the scope of our analysis to include various other glycans. There are still not many examples of functional analysis of glycans in embryonic stem cells, and we are playing a pioneering role in this field.
(3) Functional analysis of PAPS transporter knockout mice
PAPS transporters are essential for the sulfation of glycans and proteins, and without them, each molecule cannot be modified by sulfation. We first isolated and identified them in 2003. Currently, we are creating knockout mice and analyzing them. We have found that these mice develop various diseases, and we are currently analyzing the mechanisms of their onset.
(4) Functional analysis of glycan-related genes involved in undiagnosed diseases
Based on the analysis conducted so far, it has been predicted that glycans are involved in many rare undiagnosed diseases, so we have begun analyzing these as well. We will analyze the loss of function of glycan-related genes with mutations that have been found to be associated with diseases using model organisms, stem cell differentiation systems, organoids, etc., to clarify the relationship with diseases.
