About us

   Our laboratory was established in 2013. Using human induced pluripotent stem cells (iPSCs) and iPSCs induction technology, we aim to help cure various diseases, mainly including cancers that are unresponsive to conventional therapies. Our current research projects are as follows:

1.Characterization of cancer stem cells (CSCs) by the induction of CSC properties in cancer cells
   using defined factors

   Cancer stem cells (CSCs) are considered responsible for the dismal prognosis of cancer patients. However, little is known about the molecular mechanisms underlying the acquisition and maintenance of CSC properties in cancer cells because of their rarity in clinical samples. We introduced a set of defined factors (OCT3/4, SOX2 and KLF4) into human colon cancer cells and induced CSC properties in cancer cells (iCSCs). In addition, we established a novel technology for isolating and collecting these iCSCs based on the differences in the degree of the dye-effluxing activity enhancement.
(Oshima et al., 2014, PMID: 25006808)

   This novel method enables us to obtain abundant materials of CSCs that not only have enhanced tumorigenicity, but also can differentiate into a specific types of cancer tissue. We are currently establishing iCSCs from cancer cells other than colon cancer and characterizing highly-purified iCSCs. to further understand CSCs and develop new therapies targeting CSCs.

2.Construction of a carcinogenesis model using differentiated cells from human iPS cells

   In our laboratory, we are working to optimize the protocol for inducing the differentiation of human iPS cells into a variety of cells. By conducting gene introduction or gene knockout in the obtained cells, we can then construct a model to help determine the mechanism of carcinogenesis. In addition, we are also working on developing a cancer immunotherapy using human iPS cells.

3.Identification of new functions of human endogenous retrovirus using iCSCs and differentiation
   induction systems from human iPS cells

   Human endogenous retrovirus (HERV) was incorporated into the genomic DNA of our ancestors in ancient times. However, many repeat mutations and deletions are inactivated in the course of evolution. We found that some HERV-H-related genes are activated in some pluripotent stem cells and related to defective phenotypes that remain undifferentiated cells after neural differentiation and form teratomas after transplantation into mouse brain (Koyanagi-Aoi & Ohnuki et al, 2013, PMID:. 24259714). HERV-H has been reported to be activated even in some cancer cells, but the specific mechanisms and the significance of activation are not known. Using iCSCs, disease-specific iPSCs, and differentiation induction system from iPSCs, we hope to clarify new functions of HERV, including its activity in causing cancer and autoimmune diseases (bad aspects of HERV) or life-support roles (good aspects of HERV).

4.Reproduction of pathological conditions using disease-specific iPS cells and their application in drug
   discovery

   Through collaboration with other departments in Kobe University Hospital, we have established disease-specific iPS cells, differentiated them into target cells, and reproduced pathological conditions. We apply these cells to discover new drugs and clarify pathogenic mechanisms.