Development of leukemia stem cell-targeted therapy utilizing the power of innate immunity

Using various murine leukemia models and patient-derived xenograft (PDX) models, we have studied the characteristics of leukemia stem cells, which are at the root of leukemia initiation and relapse. Recently, we have shown the importance of innate immunity, including NK cells, in eradicating leukemia stem cells. We are currently developing leukemia therapies that utilize innate immune cells such as NK cells and macrophages.

Investigation of Critical Regulators in Leukemia using the CRISPR/Cas9 Library Screening

Various CRISPR/Cas9-based screens have dramatically increased the amount of information available about genes that regulate cancer growth. However, most screens have been performed in vitro. Therefore, there is still a lack of information on molecules that regulate cancer initiation and progression in vivo through interactions with the tumor microenvironment and immune cells. We are performing in vivo CRISPR/Cas9 library screens using various mouse leukemia models developed in our laboratory to search for molecules that regulate leukemia development in vivo.

Development of Blood Cell Modification Technology using Lipid Nanoparticles

Lipid nanoparticles (LNPs) are attracting attention as a promising method for delivering nucleic acids to target cells, but for practical application of nucleic acid drugs using LNPs, it is important to maximize delivery efficiency to target cells while inhibiting delivery to other organs. In collaboration with Toshiba Corporation, we are developing LNPs that maximize the efficiency of RNA delivery to various blood cells, including hematopoietic stem cells, NK cells, and leukemia cells. We are using these LNPs to develop gene therapy targeting hematopoietic stem cells and RNA-targeted therapy to treat leukemia.

Drug Discovery Research Targeting “Undruggable” Molecules

Transcription factors and epigenomic factors play a central role in the development and progression of hematologic cancers, but many are "undruggable" molecules for which inhibitors are difficult to develop. We are trying to develop new drugs targeting transcriptional and epigenomic factors using state-of-the-art technology to regulate protein-protein interactions. We are also developing novel protein degraders for the treatment of leukemia.

Blood Cell Regulation to achieve Healthy Aging

Blood cells, which circulate throughout the body, affect the functions of many organs and are involved in the onset and progression of various diseases. By analyzing "clonal hematopoiesis", which is often observed in healthy elderly people, we have clarified the mechanisms by which blood cell abnormalities promote the development of various diseases, such as solid tumors and cardiovascular diseases. Based on these findings, we are developing methods to achieve healthy aging through blood cell regulation.