Stem cell biology, Hematopoiesis, Developmental biology, Feto-maternal regulation
The process of tissue regeneration and organ development are tightly regulated by complex mechanisms. Stem cells play major roles in these events, which are controlled at multiple levels. Disruption of the system has huge risks resulting in malignant transformation and developmental failure. Our team has previously reported that proper control of protein folding is crucial for hematopoietic stem cells (HSC) in order to inhibit elevation of unfolded protein response (UPR), and bile acid can support protein folding as a molecular chaperone. Importantly, we have demonstrated that maternal bile acid is an essential factor for fetal hematopoietic stem cells to expand in the fetal liver. Thus, we are particularly interested in proteostatic and metabolic controls of stem cell regulation and feto-maternal regulation during the organ development. Our research output is expected to contribute to future stem cell therapies and improvement of pregnancy complications.
Our research therefore focuses on the following topics:
1. Investigating proteostatic controls in HSC
2. Discovering novel roles of bile acid and oxysterol in fetal organ development
3. Developing advanced technologies allowing efficient generation/expansion of HSC and red blood cells ex vivo
Hematopoietic stem cell (HSC), unfolded protein response (UPR), endoplasmic reticulum (ER) stress, bile acid, oxysterol, feto-maternal correlation, fetal growth retardation (FGR), manufactured red blood cell (RBC)
Kenichi Miharada, Ph.D, graduated Ibaraki University, Japan, and obtained his Ph.D degree from Tsukuba University, Japan, in 2007, under supervision of Prof. Toshiro Nagasawa (Tsukuba Univ.) and Dr. Yukio Nakamura (RIKEN BioResource Center) for his studies on erythropoiesis. He continued his research at RIKEN as a Special Postdoctoral Researcher in the Nakamura lab, and then moved to Lund University, Sweden in 2009. Under supervision of Prof. Stefan Karlsson, Division of Molecular Medicine and Gene Therapy, he led projects discovering novel HSC regulators. Since 2013, Dr. Miharada has started his own research group as a principal investigator (PI) at Lund Stem Cell Center for studying regulation of UPR in HSC. Since 2021, he has become a member of IRCMS as a professor, and started a new lab. Dr. Miharada aims to build novel concepts through exploring unexpected connections between a variety of findings.