Research Projects

Hematopoietic stem cells (HSCs) are a well-studied stem cell population with potential for clinical use. However, due to donor involvement and the rarity of HSC populations in bone marrow, their true potential has not been fully realized. Alternative sources of HSCs, such as pluripotent stem cells (PSCs) and umbilical cord blood (UCB), have been explored, but challenges such as maturation state and delayed engraftment remain. Ex vivo expansion of engraftable HSC populations could provide a breakthrough for broadening their use. Extensive studies have been conducted to identify cell-intrinsic and -extrinsic regulatory factors. The importance of vasculature has been reported significantly in hematopoietic niche studies. A role of VEGF signaling in hematopoiesis was hypothesized, but no study has confirmed a direct effect. To identify novel regulators of HSC function, RNASeq-based gene expression analysis was performed on HSCs from different stages of the fetal liver and dormant adult HSCs. The researchers hypothesize that VEGF signaling plays an important role in the creation of the HSC pool during development. Experiments will be performed to characterize the molecular players underlying the interaction between HSCs and their niche. Gain-of-function studies on the effect of VEGF ligands will be performed using a serum-free culture-based model. In vitro and in vivo hematopoietic assays will be performed to examine the impact of activation of signaling events. Genetic approaches involving transgenic mouse models with conditional deletion of the VEGF receptor gene will be used to confirm the mediation of VEGF signaling.