Our long-term objective is to understand the pathogenesis of leukemia at molecular level and to develop novel targeted therapeutic approaches. We have used mouse models to study the genetic control of leukemogenesis and hematopoiesis. We have generated mice with knock-in of full length and five CBFB-MYH11 constructs with deletions of functional domains and developed chemical compounds. Our original advocacies from our findings are “RUNX1 dominant inhibition independent leukemogenesis” We will establish the “Oncology” to provide a new antitumor agent showing an excellent antitumor effect against various malignant tumors.
Research and EducationWhat is in common of all the mechanisms of CBFβ-SMMHC action mentioned is that CBFβ-SMMHC binds to RUNX1 complex and insufficiently blocks its function. Many tried to up-regulate and activate RUNX1 complex function, unfortunately end in failure, since “RUNX1 dominant inhibition dependent leukemogenesis” is not enough, based on my finding “RUNX1 dominant inhibition independent theory”.
We propose to define genetic and epigenetic programs that control the self renewal properties associated with leukemias and other cancers such as glioma, prostate cancer. Our knowledge will be then used to develop new therapeutic development. Our experiments incorporate the use of many original mouse models of leukemia and characterization of primary human leukemia cells.
Current active research areas include:
- Identification of common developmental pathways that are responsible for cancer stem cell and studying their specific roles in the process.
- Developing novel therapeutic reagents by using NIH MLP/HTS.
- Generating and analysis of novel targeted transgenic mouse model.
- Japan-U.S. innovative drug development, innovation base development
- International medical human resource exchange project.
|Our original animal models：
Inv16 deletions knock-in mice models and zebra-fish models.
Yasuhiko Kamikubo M.D.,Ph.D. Associate Professor
Francis Collins M.D.,Ph.D. NIH Director
Paul Liu M.D.,Ph.D. NHGIR Deputy Scientific Director
Publications1.Ken Morita, Kensho Suzuki, Shintaro Maeda, Akihiko Matsuo, Yoshihide Mitsuda, Chieko Tokushige,・・・ Souichi Adachi, Hiroshi Sugiyama, and Yasuhiko Kamikubo: Genetic regulation of the RUNX transcription factor family has antitumor effects. J Clin Invest. 2017 May 22.
2.Kamikubo Y, Sood R, Liu PP: Role of RUNX1 in hematological malignancies. Blood. 2017 Apr 13;129(15):2070-2082.
3.Kamikubo Y, Hyde RK, Zhao L, Alemu L, Rivas C, Garret L, Liu PP: The C-terminus of CBFβ-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis. Blood 2013 121(4): 638-42.
4.Kamikubo Y, Zhao L, Wunderlich M, Corpora T, Hyde RK, Paul TA, Kundu M, Garrett L, Compton S, Huang G, Wolff L, Ito Y, Bushweller J, Mulloy JC, Liu PP: Accelerated leukemogenesis by truncated CBF beta-SMMHC defective in high-affinity binding with RUNX1. Cancer Cell. 2010 17(5): 455-68.
5.Hyde RK, Kamikubo Y, Anderson S, Kirby M, Alemu L, Zhao L, Liu PP: Cbfb/RUNX1 repression-independent blockage of differentiation and accumulation of Csf2rb-expressing cells by Cbfb-MYH11. Blood 2010 115(7): 1433-43.
LaboratoryAssociate Professor：Yasuhiko Kamikubo