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NUS Graduate School for Integrative Sciences and Engineering Research Project Write-up Title of Project 1 : Name of Supervisor: Contact Details: Manipulation of the hematopoietic stem cell (HSC) niche for the ex vivo expansion of HSCs Toshio Suda +65 6516 1166 Email : [email protected] Short Description Hematopoietic stem cells (HSCs) in the BM are regulated in a specialized microenvironment, the stem cell niche. Signals from the niche along with cell autonomous regulations are necessary for the self-renewal and proliferation of HSCs. In this project we aim to characterize cell components in the niche and identify novel factors produced by niche cells involved in the maintenance of HSCs. Identification of such factors will provide essential keys for the manipulation and expansion of HSCs, ex vivo, and allow usage of HSCs in clinical therapies for blood-related diseases. Title of Project 2 : Elucidation of niche involvement in the pathophysiology of hematopoietic malignancies along with the identification of molecular targets of diseases. Short Description Resembling solid tumor cells, leukemic stem cells (LSCs) are situated in a hypoxic environment. We found recently that leukemic cells specifically upregulates hypoxic inducible factors (HIFs) and other genes that regulate cell-cell interaction. These targets might represent a novel mechanism in how tissue metabolic status connecting to cellular interaction. Title of Project 3 : Identification of stemness-related cis-regulatory elements Short Description Gene expression is regulated by promoters and distal cis-regulatory elements. Enhancers are more cell type specific in comparison to promoters, and it is known that even genes expressed broadly can show a vast difference in enhancer usage across distinct differentiation stages. However, the nature of enhancer usage in HSC is unclear. To dissect the cellular and molecular character of HSCs, we are seeking stemness-related cis-regulatory elements, combining in silico screening and further validation of in vivo functionality using zebrafish and mice. Title of Project 4: Establishment of human stem cell niche in immunodeficient mouse Short Description Patient-derived leukemic xenograft model is important tool for basic as well as translational research. Successful xenograft remains difficult, possibly due to the lack of human niche components for leukemic cells. By implanting human niche cells, we are establishing in vivo, humanized bone marrow model in immunodeficient mice.