Kyunghee Choi, Ph.D.

Professor
Pathology and Immunology

Developmental, Regenerative and Stem Cell Biology Program
Immunology Program
Cancer Biology Program
Molecular Cell Biology Program

  • 314-362-8716

  • 314-362-9045

  • 314-747-0809

  • 8118

  • BJCIH 8th floor, room 8302

  • kchoi@wustl.edu

  • Cell fate, transcription factors, hematopoiesis, vascular, development, regeneration, stem cells, tumor angiogenesis, tumor immunity

  • Hematopoietic and endothelial development and the interplay between angiogenesis and immunity in cancer

Research Abstract:

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). We recently reported that Etv2 is reactivated in hematopoietic and endothelial cells upon injury. Importantly, Etv2 reactivation is required for vascular (Park et al., ATVB, 2016) and hematopoietic regeneration (Xu et al., JEM, 2017). We are currently 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).

Selected Publications:

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.
Full text: http://stm.sciencemag.org/cgi/content/full/13/583/eabb6731?ijkey=dJHvugdFavOCc&keytype=ref&siteid=scitransmed
Reprint: http://stm.sciencemag.org/cgi/rapidpdf/13/583/eabb6731?ijkey=dJHvugdFavOCc&keytype=ref&siteid=scitransmed

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.

Zhao, H. and Choi, K. 2019.Single cell transcriptome dynamics from pluripotency to FLK1+ mesoderm. Development. 146(23). pii: dev182097. doi: 10.1242/dev.182097.

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.

Last Updated: 7/17/2018 11:23:40 AM

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