Stem Cell Metabolism
Many of biological activities in cells, for example differentiation and proliferation, are regulated at different levels. In addition to the classical “Central dogma” flow (DNA to RNA to protein), modification of proteins and metabolic change could critically affect cellular character and fate. Stem cells – having self-renewal capacity and multi-lineage differentiation potential – have unique and distinct regulatory mechanisms to sustain such stem cell specific-ability. On the other hand, stem cells are also vulnerable to some kinds of stress factors that could severely impair capacity of stem cells. Disruption of those systems directly and indirectly leads to severe abnormality, resulting in serious diseases including cancer.
In our group, we are particularly interested in how protein stability control and metabolic regulation influence the fate choice and proliferation of stem cells, and how it is managed at different situations – e.g. quiescent condition, regeneration and development. We utilize hematopoietic stem cells, red blood cell production (erythropoiesis) and embryonic development as model systems to discover previously unknown mechanisms governing complicate biological activities. Especially, we are focusing on bile acid and oxysterols, which were almost exclusively known as a part of lipid absorption and metabolism but we have revealed their importance in regulation of hematopoietic stem cells.
- To investigate roles and regulation of protein quality control in hematopoiesis
- To discover novel mechanisms governing organ/tissue development during pregnancy
- To establish methods to generate abundant red blood cells ex vivo by controlling stem cell expansion and differentiation
Protein quality control and metabolic regulation are involved in a variety of biological activities, and failure in the system has been implicated in many types of diseases. For example, we have previously demonstrated that fetal bile acid, mainly supplied from the maternal body during pregnancy, is a crucial factor to support expansion of hematopoetic stem cells in the fetal liver by suppressing an elevation of unfolded protein stress (Sigurdsson et al. Cell Stem Cell, 2016). Thus, our research will uncover previously undiscovered regulatory systems which are expected to result in developing new therapies for complicate and serious diseases.
(name linked to profile in Lund University research portal)
Principal investigator, Assistant professor, Kenichi [dot] Miharada [at] med [dot] lu [dot] se
Visiting research fellow, youichi [dot] haga [at] med [dot] lu [dot] se
Postdoctoral fellow, visnja [dot] radulovic [at] med [dot] lu [dot] se
Postdoctoral fellow Kiyoka [dot] Saito [at] med [dot] lu [dot] se
Assistant researcher, valgardur [dot] sigurdsson [at] med [dot] lu [dot] se
PhD student, svetlana [dot] soboleva [at] med [dot] lu [dot] se