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.
- Kobayashi H, Kobayashi CI, Nakamura-Ishizu A, Karigane D, Haeno H, Yamamoto KN, Sato T, Ohteki T, Hayakawa Y, Barber GN, Kurokawa M, Suda T, Takubo K. Bacterial c-di-GMP affects hematopoietic stem/progenitors and their niches through STING. Cell Rep. 11(1):71-84, 2015
- 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
- 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
- Nakamura-Ishizu A, Takizawa H, Suda T: The analysis, roles and regulation of quiescence in hematopoietic stem cells. Development 15: 4656-66, 2014
- Ito K, Suda T: Metabolic requirements for the maintenance of self-renewing stem cells. Nat Rev Mol Cell Biol 141: 243-56, 2014
- Okabe K, Kobayashi S, Yamada T, Kurihara T, Tai-Nagara I, Miyamoto T, Mukouyama YS, Sato TN, Suda T, Ema M, Kubota Y: Neurons limit angiogenesis by titrating VEGF in retina. Cell : 159: 584-96, 2014
- Kobayashi I, Kobayashi-Sun J, Kim AD, Pouget C, Fujita N, Suda T, Traver D: Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling. Nature 512: 319-23, 2014
- Tai-Nagara I, Matsuoka S, Ariga H, Suda T: Mortalin and DJ-1 coordinately regulate hematopoietic stem cell function through the control of oxidative stress. Blood 123: 41-50, 2014
- Kobayashi CI, Takubo K, Kobayashi H, Nakamura-Ishizu A, Honda H, Kataoka K, Kumano K, Akiyama H, Sudo T, Kurokawa M, Suda T: The IL-2/CD25 axis maintains distinct subsets of chronic myeloid leukemia-initiating cells. Blood 123: 2540-9, 2014
- Takubo K, Nagamatsu G, Kobayashi CI, Nakamura-Ishizu A, Kobayashi H, Ikeda E, Goda N, Rahimi Y, Johnson RS, Soga T, Hirao A, Suematsu M, Suda T: Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell 12: 49-61, 2013
|Affiliations||Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Professor, Department of Medicine, Yong Loo Lin School of Medicine, NUS
|sudato[at]z3.keio.jp / csits[at]nus.edu.sg|
|Institute||Degree (if applicable)||Year(s)|
|Jichi Medical School||PhD||1985|
|Yokohama City University, Japan||MD||1974|
|•||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|
Directed differentiation of pluripotent stem cells towards hematopoietic stem cells.
To elucidate the pathophysiology of stem cell niche through the identification of stemness-related cis-regulatory elements using zebrafish and transgenic mouse as models.
To delineate the niche through the identification of cell specific production of Thrombopoietin (TPO), which regulating HSC quiescence.
Imaging study on the interaction between stem cells and niche
Jessica Leonie K BERLIER
Relationship between the mesenchymal stem cells (MSC) and the hematopoietic stem cell (HSC) niche
Investigate the potential role of glycol and lipid metabolism in hematopoietic stem cell
Therapeutic approaches to stem cell niche
To elucidate the role of cellular energy metabolism for maintaining hematopoietic stem cell homeostasis
To elucidate the mechanisms of megakaryopoiesis and thrombopoiesis through thrombopoietin signalling in haematopoietic stem cells
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|