| Research Interests
|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.
|1. Elucidation of molecular mechanism of pancreatic beta- cell development and its application.
Insulin is the only pancreatic β-cell hormone capable to lower blood glucose concentrations. Our group is interested in the molecular mechanisms of pancreatic β-cell development and differentiation so that the results could be applied to the future replacement of dampened β-cells in diabetes with newly developed β-cells from other cell types.
Now, we are focusing on
|(1) To reveal the molecular mechanisms of pancreatic development and differentiation using deficient mice of large Maf transcription factor.
|(2) To reveal the functional alteration of large Maf transcription factors in diabetic state.
|(3) Direct reprogramming of hepatocytes to β-cells for future treatment of diabetes.
|(4) Identification of β-cell specific genes contributing β-cell maturation using novel genome-editing system, Crispr.
Our goal is to integrate the results of each subtopic containing different points of view and gain insight of the regulation of metabolic homeostasis for better understanding of the diabetes pathophysiology and the development of future innovative treatment.
|2. Functional analysis of large Maf transcription factor family, MafB and c-Maf in macrophage development and functions.
We study about functions of large Maf transcription factor family, MafB and c-Maf in macrophages. We have investigated that MafB is important for developing atherosclerosis, autoimmune disease that caused by macrophages. MafB is also important osteolysis caused by abnormal osteoclast development from macrophage progenitors. Now we are trying to find molecular mechanisms about them.
|3. Elucidating biological roles of carbohydrates using glycosyltransferase conditional KO mice.
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.
|4. Transcriptome analysis of mice in the space.
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.
|5. p62 and Oxidative stress
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.
|4. Notch group
To reveal the mechanism of tissue formation, we focus on cell-cell communication, especially on Notch signaling. We are trying to reveal how this signaling is acting during tissue formation by using a transgenic mouse that enabled visualization of signaling receival experience at a cellular level.
|If you are interested in our research themes, or in generating knockout mice or transgenic mice, please contact us at your convenience.