Educational Activities

Graduate school: Basic lecture III, Advanced lecture VII

Research Activities

"Curing cancer" was a dream. Today, advances in technology make it no longer a dream: A cure for cancer has become possible, even probable. Our laboratory is interested in the molecular, cellular, and genetic basis of cancers, with a specific focus on hematopoietic neoplasms.

(1) Cancer Stem Cell and Tumor Immunity
To develop curative cancer therapies, we need to eradicate cancer stem cells, the key drivers of tumor progression, therapy resistance and relapse. Recently, we identified "immune escape" as an important mechanism of leukemia stem cells to survive under the treatment of the p53-activating drug (Fig.1). We are interested in how cancer stem cells resist and survive during chemotherapy, and how cancer stem cells evade from antitumor immunity.

(2) Clonal hematopoiesis in aging and disease
Aging is associated with an accumulation of somatic mutations in hematopoietic stem cells, which results in clonal expansions of mutant blood cells (clonal hematopoiesis: CH). We are interested in the role of CH in the development of various age-related diseases, including cardiovascular diseases and solid cancers. We would also like to understand how the specific mutations promote the development of CH, which should contribute to disease prevention and health promotion in aged people.

(3) Targeting transcription and epigenetic factors through PPI modulation
Transcription factors and epigenetic regulators play pivotal roles in various types of diseases. However, most of these molecules have been considered "undruggable". We are trying to develop therapies targeting these "undruggable" molecules using the cutting-edge technology to modulate protein-protein interactions (PPI). (Fig.2).



Tumor immunity augments the antileukemia effect of p53 activation



Targeting "Undruggable" targets

Literature

1) Hayashi Y, *Goyama S, Liu X, Tamura M, Asada S, Tanaka Y, Fukuyama T, Wunderlich M, O‘Brien E, Mizukawa B, Yamazaki S, Matsumoto A, Yamasaki S, Shibata T, Matsuda K, Sashida G, Takizawa H, *Kitamura T. Antitumor immunity augments the therapeutic effects of p53 activation on acute myeloid leukemia. Nature Communications 10(1): 4869 (2019).
2) Asada S, Goyama S, Inoue D, Shikata S, Takeda R, Fukushima T, Yonezawa T, Fujino T, Hayashi Y, Kawabata KC, Fukuyama T, Tanaka Y, Yokoyama A, Yamazaki S, Kozuka-Hata H, Oyama M, Kojima S, Kawazu M, Mano H, *Kitamura T. Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis. Nature Communications 9(1): 2733 (2018).
3) Goyama S, Yamamoto G,
Shimabe M, Sato T, Ichikawa M, Ogawa S, Chiba S, *Kurokawa M. Evi-1 is a critical regulator for hematopoietic stem cells and transformed leukemic cells. Cell Stem Cell 3(2): 207-220 (2008).
4) Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, Nakagawa M, Olsson A, Wunderlich M, Link KA, Mizukawa B, Grimes HL, Kurokawa M, Liu PP, Huang G, *Mulloy JC. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. Journal of Clinical Investigation 123(9): 3876-88 (2013).

Other Activities

Councilor of Japanese Society of Hematology (2016-present)
Japanese Cancer Association
The Japanese Society of Internal Medicine

Future Plan

Based on the finding of our research, we will develop novel drugs and therapeutic strategies for hematopoietic neoplasms. We are currently developing drugs targeting transcription factors through modulation of protein-protein interactions.

Messages to Students

I hope you will get skills to design research and to write papers by yourself. I will support you to accomplish the goal.