Kyunghee Choi, PhD
Professor, Department of Pathology & Immunology
- Email: firstname.lastname@example.org
Core Usage & WUSTL affiliations:
- Pathology & Immunology Flow Cytometry Core
- Genome Technology Access Center (GTAC)
- Center for Human Immunology and Immunotherapy Program
Selected Grants and Awards:
- Children’s Discovery Institute Grant
- New England Bioscience Society, Distinguished Stem Cell Research Award
Vascular and Hematopoietic Development and Regeneration
We study hematopoietic and endothelial cell development and their interplay in cancer. We have expertise in hematopoietic, vascular, and stem cell biology, as well as stem cell applications. Notably, we focus on how hematopoietic and vascular systems are established during embryogenesis. Our contributions to this area have been delineating molecular and cellular pathways that control commitment from mesoderm to hematopoietic and endothelial cells. Specifically, the demonstration of the “Hemangioblast” is a significant contribution to the field, as this study was the first to show experimentally the presence of the long hypothesized common hematopoietic and endothelial cell progenitor “Hemangioblast” (Choi et al., Development, 1998). Subsequent studies have focused on transcription factors and signaling pathways that contribute to hemangioblast development and differentiation. Notably, we have shown that the ETS transcription factor ETV2 functions at the earliest stage of the hemangiogenic cell lineage development. We reported the first paper on this gene’s knockout phenotype, which shows a complete defect in hematopoietic and vascular development (Lee et al., Cell Stem Cell, 2008). Subsequently, we reported the ETV2 ChIP-seq study to demonstrate its essential function in establishing the hemangiogenic program (Liu et al., EMBO Reports, 2015). We recently reported that hemangiogenic fate is specified not by the onset of Etv2 expression but by a threshold-dependent mechanism, in which VEGF-FLK1 signaling plays an instructive role by controlling Etv2 threshold expression (Zhao and Choi, Nature Communications, 2017). Notably, the analysis of the fate of Flk1+ cells by single-cell RNA-sequencing suggests that the default fate of these cells is smooth muscle differentiation. This study provides a potential new regulatory mechanism that operates early in development on Flk1+ cells (Zhao and Choi, Development, 2019). Currently, we are integrating epigenetics into the study of hemangiogenesis (Wu et al., Cell Rep., 2020). By utilizing mouse tumor models, we are also investigating the mechanisms by which tumors control tumor immunity by exploiting endothelial cells locally and distally to favor the tumor progression (Kabir et al., JCI Insight, 2018; Kabir et al., Science Translational Medicine, 2021).
- Kabir, A.U., Subramanian, M., Lee, D.H., Wang, X., Krchma, K. Wu, J., Naismith, T., Halabi, C.M., Kim, J.Y., Pulous, F., Petrich, B., Kim, S., Park, H-C., Hanson, P.I., Pan, H., Wickline, S.A., Fremont, D.H., Park, C., and Choi, K. 2021. Dual role of endothelial Myct1 in tumor angiogenesis and tumor immunity. Science Translational Medicine 13(583):eabb6731.
- Wu, J., Krchma, K., Lee, H.J., Prabhakar, S., Wang, X., Zhao, H., Xing, X., Seong, R.H., Fremont, D.H., Artyomov, M.N., Wang, T. and, Choi K. 2020. Requisite Chromatin Remodeling for Myeloid and Erythroid Lineage Differentiation from Erythromyeloid Progenitors. Cell Rep. 33(7):108395.
- Kabir, A.U., Lee, T-J., Pan, H., Berry, J.C., Krchma, K., Wu, J., Liu, F., Kang, H-K., Hinman, K., Yang, L., Hamilton, S., Novack, D.V., Mecham, R.P., Wickline, S.A., Miller, M.J. and Choi, K. 2018. Requisite endothelial reactivation and effective siRNA nanoparticle targeting of Etv2/Er71 in tumor angiogenesis. JCI Insight. 3(8):e97349. doi:10.1172/jci.insight.97349.
- Zhao, H., and Choi, K. 2017. A CRISPR screen identifies genes controlling Etv2 threshold expression in hemangiogenic fate commitment. Nature Communications. 8(1):541. doi: 10.1038/s41467-017-00667-5.
- Xu, C., Lee, T., Sakurai, N., Krchma, K., Liu, F., Li, D., Wang, T. and Choi, K. 2017. ETV2/ER71 regulates hematopoietic regeneration through hematopoietic stem cell proliferation. J. Exp. Med. 214(6):1643-1653.