Motomi OSATO

Osato has been studying the molecular mechanism of leukemogenesis by RUNX and related genes, using cell biological approaches, in vivo mouse and zebrafish systems and analysis of human leukemia samples. His current interest is to develop a novel treatment for Runx leukemia.  He is also searching for cis-regulatory non-coding genomic elements associated with human leukemia and stem cells. His best known research accomplishment is the detection of point mutations in the RUNX1/AML1 gene in acute myeloid leukemia patients.

1. Leukemia research towards novel treatments

We have been interrogating the mechanistic basis for leukemogenesis through the analyses of a key leukemia gene, RUNX1, aiming for the development of novel diagnostic and therapeutic methods (Figure 1). Treatment of RUNX leukemia has a dismal outcome and novel therapeutic approaches are needed. Our experimental platforms inlcude a mouse system (knockout or transgenic mice), and molecular and cellular analyses on clinical samples. Using such strategy, we have identified many diagnostic markers and treatment methods.

2. Identification of cis-regulatory elements associated with human diseases

Human genome consists of 1.5% of coding and 98.5% of non-coding regions. Approximately 40% of disease-related genetic changes are expected to be located within the non-coding region, particularly in cis-regulatory elements (enhancer, silencer, locus control region, and insulator) which govern expression of genes. Genetic alterations in non-coding (intronic and intergenic) regions in RUNX loci have also been suspected to be the underlying mechanism for multiple human diseases; however, cis-elements for Runx family genes remain largely unknown. Employing our own unique strategy as shown in Figure 2, we have identified multiple cis-regulatory elements. Single nucleotide polymorphisms (SNPs) within these elements would serve as predictive risk factors for human diseases, whereas pharmaceutical modulation of the elements would lead to novel therapeutic directions.

Selected Publications:

  1. Matsuo J, Kimura S, Yamamura A, Koh CP, Hossain Z, Heng DL, Kohu K, Voon DCC, Hiai H, Unno M, So JBY, Zhu F, Srivastava S, Meng T, Yeoh KG, Osato M*, Ito Y*. *co-corresponding author. Identification of stem cells in the epithelium of the stomach corpus and antrum of mice. Gastroenterology 152:218-31, 2017
  2. Chin WLD, Watanabe-Okochi N, Wang CQ, Tergaonkar V, Osato M. Mouse models for Core Binding Factor leukemia. Leukemia 29:1970-80, 2015
  3. Koh CM, Bezzi M, Low HP, Ang WX, Teo SX, Gay FP, Al-Haddawi M, Tan SY, Osato M, Sabò A, Amati B, Wee KB, Guccione E. MYC regulates the core pre-mRNA splicing machinery as an essential step in lymphomagenesis. Nature 523:96-100, 2015
  4. Wang QC, Krishnan V, Tay LS, Chooi JY, Chin DWL, Koh CP, Chooi JY, Nah GSK, Du L, Jacob B, Yamashita N, Tan TZ, Mori S, Taniuchi I, Tergaonkar V, Ito Y, Osato M. Disruption of Runx1 and Runx3 leads to bone marrow failure and leukemia predisposition due to transcriptional and DNA repair defects. Cell Reports 8:767-82, 2014
  5. Koh CP, Wang QXC, Ng CEN, Ito Y, Araki M, Tergaonkar V, Huang G, Osato M. Runx1 meets MLL: epigenetic regulation of hematopoiesis by two leukemia genes. Leukemia, 27:1793-802, 2013
  6. Wang QXC, Motoda L, Satake M, Ito Y, Taniuchi I, Tergaonkar V, Osato M. Runx3 deficiency results in myeloproliferative disorder in aged mice. Blood 122:562-66, 2013
  7. Ng ELC, Yokomizo T, Yamashita N, Cirovic B, Jin H, Wen Z, Ito Y, Osato M. A Runx1 intronic enhancer marks hemogenic endothelial cells and hematopoietic stem cells. Stem Cells 28:1869-81, 2010
  8. Osato M. Point Mutations in the RUNX1/AML1 Gene: Another Actor in RUNX Leukemia. Oncogene 23:4284–96, 2004
  9. Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae S.C., Komori T, Ito Y and Littman DR. Requirement for Runx proteins in CD4 silencing at different stages of T lymphocyte development. Cell 111: 621-33, 2002
  10. Osato M, Asou N, Abdalla E, Hoshino K, Yamasaki H, Okubo T, Suzushima H, Takatsuki K, Kanno T, Shigesada K, Ito Y. Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2αB associated with myeloblastic leukemias. Blood 93:1817-24, 1999
Name Motomi OSATO
Affiliations Principal Associate, Cancer Science Institute of Singapore, National University of Singapore
Research Associate Professor, Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore
Professor, International Research Center for Medical Sciences, Kumamoto University, Japan
Email csimo[at]nus.edu.sg

Education

Institute Degree (if applicable) Year(s)
Oita Medical University, Japan MD 1990
Graduate School of Medicine, Kumamoto University, Japan Ph.D 1999

Professional Experience

Professor, International Research Centre for Medical Science, Kumamoto University 2015 – present
Research Associate Professor, Department of Pediatrics, Yong Loo Lin School of Medicine, NUS 2013 – present
Clinician Scientist, Institute of Bioengineering and Nanotechnology, A*STAR 2009 – present
Principal Associate, Cancer Science Institute of Singapore, NUS 2008 – present
Research Assistant Professor, Institute for Molecular and Cell Biology, A*STAR 2002 – 2008
Research Fellow & Instructor, Institute for Virus Research, Kyoto University, Japan 1997 – 2002

Akiko NAMBU

Adjunct Research Fellow

Antibody therapy for RUNX leukemia

Hiroki HOSOI

Academic Visitor

RUNX3 enhancer in tumorigenesis

Michelle Meng Huang MOK

Senior Laboratory Executive / PhD student

RUNX family genes in hematopoiesis and leukemogenesis

Nur Humaira bte FUA’DI

Laboratory Executive

Mouse care and flow cytometer operation