Toshio SUDA

Professor Suda has been studying hematopoietic stem cells (HSCs) and the HSC niche for more than thirty years. HSCs give rise to additional stem cells (self-renewal) and to progenitor cells (differentiation). This fate decision is determined by both cell autonomous programs and by the surrounding microenvironment, or niche. Our past work encompasses the study of the intrinsic and extrinsic regulation of HSCs, purification of potent HSCs, analyses of cell differentiation processes, identification of cytokine signaling in hematopoiesis, and the characterization of HSC niches. With that, we will aim for the regulation of stem cells by niche, or niche therapy. By focusing on the areas of stem cell niches, stem cell aging and cancer stem cells, we hope to provide novel insights to the development of niche therapy. We will further translate our findings into clinical settings, which would contribute to stem cell transplantation as well as treatment of hematological diseases.

We will base our work on the hypothesis that the bone marrow (BM) microenvironment known as the stem cells niche is essential for the maintenance of HSC quiescence in cell cycle and regulates the fate of hematopoietic stem cells (HSCs). We will aim for the regulation of stem cells by niche as niche therapy. We will dissect the niche as a functional unit of stem cell regulation, and aim to expand stem cells using ex vivo artificial niches and improve the method of BM transplantation.

First, we will dissect the cellular and molecular character of the endosteal and perivascular niches, and clarify the direct negative feedback from progenitor cells to HSCs. This will elucidate the hematopoietic homeostasis of stem cells. Second, we hope to develop methods for maintaining and expanding stem cells ex vivo by reducing mitochondrial reactive oxygen species production.

This process will involve the integration of various methodologies including metabolome analysis,bio-imaging and bioinformatics. Especially, we will establish state-of-the-art metabolomics technology in HSCs in NUS.

We will also clarify whether stem cell- and niche-aging relates to pathogenesis of malignancies. We will identify leukemic and multiple myeloma stem cells and their niches in seeking to develop a novel treatment for these intractable diseases. We will further study abnormal cytokine networks in chronic myelogenous leukemia and the vascular and osteoblastic niches in myeloma. Migration of cancer stem cells is another challenge with potentially high impact. We will extend our study on HSC migration to cancer metastasis by introducing the concept of epithelial cell suppression for stem cell expansion. Moreover, we investigate the onset and progression of myelofibrosis and other fibrotic disorders (liver cirrhosis and pulmonary fibrosis). These studies will elucidate the pathophysiology of diseases and would provide critical clues to develop novel treatment and preemptive measures for the diseases.

Selected Publications:

  1. Baba M, Endoh M, Ma W, Toyama H, Hirayama A, Nishikawa K, Takubo, K, Hasumi H, Umemoto T, Hashimoto M, Irie N, Esumi C, Kataoka M Hano H, Nakagata N, Soga T, Yao M, Kamba T, Minami T, Ishii M, Suda T., Folliculin regulates osteoclastogenesis through metabolic regulation. J Bone Mineral Res, 2018 Jun 12. doi: 10.1002/jbmr.3477
  2. Umemoto T, Hashimoto M, Matsumura T, Nakamura-Ishizu A, Suda T.:, Ca2+-Mitochondrial axis drives cell division in hematopoietic stem cells. J Exp Med, 2018 Jun 26. pii: jem.20180421. doi: 10.1084/jem.20180421.
  3. Yang C and Suda T.: Hyperactivated mitophagy in hematopoietic stem cells. Nat Immunol. 19:2-3, 2018
  4. Vu TM, Nakamura-Ishizu A, Foo JC, Torta, FT, Toh XR, Whee DM, Fangyu Z, Cazenave-Gassiot A, Shiow S-A TE , Suda T., Silver DL, Wenk M, Nguyen LN, Mfsd2b is the exporter of sphingosine-1-phosphate in erythrocytes and platelets. Nature, 550:524-528, 2017
  5. Tan DQ, Suda T.: Reactive oxygen species and mitochondrial homeostasis as regulators of stem cell fate and function. Forum Review, Antioxid Redox Signal. 2017 Oct 26. doi: 10.1089/ars.2017.7273.
  6. Umemoto T, Matsuzaki Y, Shiratsuchi Y, Hashimoto M, Yoshimoto T, Nakamura-Ishizu A, Petrich B, Yamato M, Suda T. Integrin αvβ3 enhances the suppressive effect of interferon-γ on hematopoietic stem cells. EMBO. J. 36(16):2390-2403.2017
  7. Hosokawa K, MacArthur BD, Matsumoto-Ikushima Y, Toyama H, Masuhiro Y, Hanazawa S, Suda T., Arai F: Pot1 maintains hematopoietic stem cell activity under stress. Nat Comm
    2017 Oct 6;8(1):804. doi: 10.1038/s41467-017-00935-4
  8. Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G, Kubota Y, Goda N, Matsumoto M, Nishimura EK, Soga T, Otsu K, Suematsu M, Okamoto S, Suda T., Takubo K. p38α activates purine metabolism to initiate hematopoietic stem/progenitor cell cycling in response to stress. Cell Stem Cell. 19:192-204, 2016
  9. Nakamura-Ishizu A, Takubo K, Kobayashi H, Suzuki-Inoue, Suda T.: CLEC-2 in megakaryocytes is critical for maintenance of hematopoietic stem cells in bone marrow. J Exp Med, 212: 2133-2146, 2015
  10. Yamashita M, Nitta E, Suda T. Aspp1 preserves hematopoietic stem cell pool Integrity and prevents malignant transformation. Cell Stem Cell. 17(1):23-34, 2015
Name Toshio SUDA
Affiliations Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Professor, Department of Medicine, Yong Loo Lin School of Medicine, NUS
Email sudato[at]z3.keio.jp / csits[at]nus.edu.sg

Education

Institute Degree (if applicable) Year(s)
Jichi Medical School PhD 1985
Yokohama City University, Japan MD 1974

Professional Experience

Senior Principal Investigator, Cancer Science Institute of Singapore, NUS 2013 – Present
Professor, Developmental Biology, The Sakaguchi Laboratory, School of Medicine, Keio University 2002 – 2015
Professor, Dept. of Hemopoiesis School of Medicine, Kumamoto University 1992 – 2002
Associate Professor, Hematology, Jichi Medical School 1991 – 1992
Assistant Professor, Hematology, Jichi Medical School 1984 – 1991
Research Associate, Div. of Hemopoiesis, Medical University of South Carolina 1982 – 1984
Research Associate, Div. of Hemopoiesis, Jichi Medical School 1978 – 1982

Mitsuhiro ENDO

PhD
Senior Research Scientist

csime[at]nus.edu.sg

Directed differentiation of pluripotent stem cells towards hematopoietic stem cells.

Takayoshi MATSUMURA

MD, PhD
Senior Research Scientist

csitkm[at]nus.edu.sg

To elucidate the pathophysiology of stem cell niche through the identification of stemness-related cis-regulatory elements using zebrafish and transgenic mouse as models.

Ayako NAKAMURA-ISHIZU

MD, PhD
Senior Research Scientist

csiai[at]nus.edu.sg

To delineate the niche through the identification of cell specific production of Thrombopoietin (TPO), which regulating HSC quiescence.

Yuji TAKIHARA

MD, PhD
Senior Research Scientist

ytakihara[at]nus.edu.sg

Imaging study on the interaction between stem cells and niche

Jessica Leonie K BERLIER

Research Fellow

csijlkb[at]nus.edu.sg

Relationship between the mesenchymal stem cells (MSC) and the hematopoietic stem cell (HSC) niche

YANG Chong

Research Fellow

csiyc[at]nus.edu.sg

Investigate the potential role of glycol and lipid metabolism in hematopoietic stem cell

Muddineni Siva Sai Naga ANURAG

Research Assistant

csimssna[at]nus.edu.sg

To elucidate dysregulated mechanisms in malignant hematopoiesis

A’qilah BANU

Research Assistant

csiabbam[at]nus.edu.sg

Therapeutic approaches to stem cell niche

Tamie ENDO

Laboratory Executive

csiet[at]nus.edu.sg

To elucidate the role of cellular energy metabolism for maintaining hematopoietic stem cell homeostasis

Aled O’NEILL

PhD Student

aled[at]u.nus.edu

To elucidate the mechanisms of megakaryopoiesis and thrombopoiesis through thrombopoietin signalling in haematopoietic stem cells

Darren TAN

PhD Student

a0074009[at]u.nus.edu

Metabolic function of PRMT5 in hematopoietic stem cells

Japanese Society of Hematology (JSH) Award 2013
Donald Metcalf Award by International Society of Experimental Hematology (ISEH) 2014