| In our laboratory, we are working on the functional analysis of transcription factors in the body by employing developmental engineering such as generating transgenic mice. We are focusing on the following research themes. |
Our research group, the "MafA c-Maf Group" focuses on the Large MAF family of transcription factors—particularly MafA and c-Maf—by utilizing genetically modified mice, including conditional knockout and point mutation models, to identify and analyze various abnormal phenotypes.
MafA point mutation mice: The mice develop diabetes, which subsequently progresses to renal cancer—a remarkably rare and unique phenotype.
c-Maf conditional knockout mice: The loss of c-Maf has shown a potential therapeutic effect on chronic kidney disease and its associated cardiovascular complications.
c-Maf point mutation mice: The mice exhibit symptoms of Ayme-Gripp syndrome, a rare congenital disorder. The wide range of abnormalities suggests that c-Maf plays critical roles in various tissues.
Our group conducts a broad spectrum of research projects, ranging from phenotypic analysis of the mice to the elucidation of disease mechanisms and the development of novel therapeutic strategies.
Our group aims to elucidate the fundamental molecular mechanisms underlying biological phenomena using molecular biology techniques, genetically modified mice, and live imaging technologies. We particularly focus on the functions of Maf family transcription factors and macrophages in development, differentiation, metabolism, and disease pathogenesis.
Macrophages are essential immune cells for host defense and homeostasis, but their dysfunction can contribute to various diseases. We have been studying the role of the transcription factor MAFB in macrophages. We previously demonstrated that MAFB promotes atherosclerosis by inhibiting foam cell apoptosis (Hamada et al., Nat Commun. 2014) and regulates the expression of complement C1q (Tran et al., Nat Commun. 2017). More recently, we found that MAFB is involved in the regulation of inflammatory lipid mediators during ischemic acute kidney injury (Kanai et al., J Immunol. 2024) and in controlling neuronal density in brown adipose tissue (BAT) in response to cold exposure (Yadave et al., Cell Rep. 2024). MAFB has also been suggested as a potential prognostic biomarker in lung adenocarcinoma (Omar et al., Int J Mol Sci. 2022). These findings guide our efforts to further elucidate novel disease mechanisms involving MAFB.
The physiological roles of the carbohydrate moieties remain poorly understood. Glycosyltransfeases catalyze the transfer of a monosaccharide from a donor sugar nucleotide onto an acceptor saccharide in ER and Golgi apparatus. We aim to unravel biological roles of the carbohydrates and glycoproteins by analyzing phenotypes of glycosyltransferase conditional knockout mice. Currently we focus on two themes below.
(1) Investigation of roles of mucin type O-glycans and identification of functional glycoproteins for megakaryocyte differentiation. (2) Contribution of chondroitin sulfate to endochondral ossification.
Alterations of gene expression pattern in each mouse organ under long stay in the space will be analyzed. We believe that these results can contribute to measure against aging by the mechanism elucidation of bone mass reduction and muscle atrophy, and radiation protection study on the biological influence under long-term radiation exposure.
p62 was found as an oxidative stress inducible gene.
Recently, it has demonstrated that p62 has important biological functions in a selective autophagy pathway and involved in the formation of intracellular protein aggregates seen in various diseases.
With mutant p62-expressing mice, we aim to elucidate novel functions of p62 and mechanisms of disease pathogenesis focusing on intracellular localization of p62, degradation of ubiquitinated protein and liquid-liquid phase separation.
Our group is interested in the mechanisms in which well-organized tissues are formed from undifferentiated cells via signal transduction. Focusing on Notch signaling pathway, we use transgenic technologies to create a new standard in developmental biology in which signal transduction and signaling molecules are clearly distinguished.