Investigating the molecular mechanism of HIF in hypoxic stress

The top three causes of death in Japan are malignant tumor, ischemic heart disease, and cerebral vascular disease. A common cause of these diseases is low oxygen tension in our body, known as hypoxic stress. The key transcription factors that regulate response to hypoxic stress are the Hypoxia Inducible Factors (HIFs). There are 3 types of HIFs: HIF-1α are expressed ubiquitously, HIF-2α are mainly expressed in endothelial cells, and HIF-3α works as an inhibitor against HIF-1α and HIF-2α.

In our laboratory, we investigate the molecular mechanisms of HIFs for hypoxic responses in vivo. We investigate the roles of HIF-2α for tumor vascularization, erythropoiesis, retinopathy of prematurity using HIF-2α knockdown mice. We also analyze the roles of HIF-3α for pulmonary hypertension and lung development using HIF-3α knockout mice. We try to clarify the diversity of HIF functions in response to various hypoxic stimuli.

Analysis of functional adult stem cells and progenitor cells for clinical application

Adult stem cells are undifferentiated cells, found in  adult tissues, which have stem cell characteristics such as self-renewal and differentiation potency. Since the use of embryonic stem cells is controversial, researchers are now investigating adult stem cells as a source of cells for application in regenerative medicine, the goal of which is to replace the dysfunctional cells in the tissue or support in the recovery of local cells. However, the self-renewal, proliferation, and other properties of the various adult stem cells are different so it is necessary to properly analyze their characteristics and their potency before applying adult stem cells in clinical treatment for specific disease.

In our laboratory, we are focusing on  the analysis of the biological characteristics and functions of mesenchymal stem cells and endothelial progenitor cells from several sources for application in future clinical treatments. Furthermore, we are aiming to clarify the underlying mechanisms regulating mesenchymal stem cells and endothelial progenitor cells in order to support tissue or organ recovery.

Researching the relationship between cancer and stem cells

To cure cancer, it is necessary to understand how cancer cells interact with local resident cells, including stem cells.

Our lab is researching how cancer cells 'communicate' with tissue stem cells using breast cancer cell lines and human tissue-derived messenchymal stem cells.