Eunhee Choi, PhD
- Assistant Professor of Pathology & Cell Biology
Credentials & Experience
Education & Training
- PhD, Seoul National University
- Fellowship: University of Texas Southwestern Medical Center
The goal of our research is to delineate mechanisms underlying the mutual regulation between cell division and metabolism by combining mouse genetics, cell biology, biochemistry and cryo-EM structure. Perturbation of this regulation leads to cancer and metabolic diseases. We have discovered a critical role of cell division regulators in insulin signaling through regulating insulin receptor endocytosis. Our findings link aneuploidy-suppressing genes to insulin signaling and suggest a mechanism by which a circulating hormone may regulate genomic stability. Our laboratory will study the role of cell division regulators in insulin signaling, and we will expand it to other receptor tyrosine kinases to discover how systemic signaling communicates with cell division process to maintain both genomic stability and metabolic homeostasis.
Recently, we discovered that large-scale conformational change of insulin receptor driven by insulin binding relieves its auto-inhibition, triggering trans-autophosphorylation of the kinase domain and hence initiation of downstream signaling cascade. How this conformational change induces kinase activation, how the activated kinase selectively provokes the signaling branch, and how the active insulin receptor can be preferentially internalized are not fully understood. Our laboratory will reveal how insulin activates the receptor kinase and insulin signaling, and initiates the receptor endocytosis at the molecular level, and how this process maintains systemic homeostasis in vivo. Along the way, we hope to unravel new molecular targets that will be useful to treat two very prevalent diseases, Diabetes and Cancer.
Welcome to Choi Lab
- The mutual regulation between cell division and metabolism, and its impact on physiology
- Park J., Hall C., Hubbard B., LaMoia T., Gaspar R., Nasiri A., Li F., Zhang H., Kim J., Haeusler R., Accili D., Shulman G., Yu H., and Choi E. (2023) MAD2-dependent insulin receptor endocytosis regulates metabolic homeostasis. Diabetes. db230314 https://doi.org/10.2337/db23-0314
- Wang L.#, Hall C.#, Uchikawa E., Chen D., Choi E.*, Zhang X.*, Bai XC.* (2023) Structural basis of insulin fibrillation. Science Advances. 9, eadi1057 https://pubmed.ncbi.nlm.nih.gov/37713485/ (#Co-first, *Co-corresponding author)
- Wei L.#, Hall C.#, Li J., Choi E.*, and Bai XC.* (2023) Structural basis of the alkaline pH-dependent activation of insulin receptor-related receptor. Nature Structural & Molecular Biology. https://doi.org/10.1038/s41594-023-00974-0 (#Co-first, *Co-corresponding author)
- Hung A. and Choi E. (2023) How to control Hunger. Nature Structural & Molecular Biology. 30, 409-411. https://www.nature.com/articles/s41594-023-00963-3
- Choi E*., and Bai XC*. (2023) Activation mechanism of the insulin receptor: a structural perspective. The Annual Review of Biochemistry. (Invited review, Editor: Dr. Roger Kornberg). Online ahead of print. https://www.annualreviews.org/doi/pdf/10.1146/annurev-biochem-052521-033250 (*Co-corresponding author)
- Li J., Wu J., Hall C., Bai XC.*, Choi E.* (2022) Molecular basis for the role of disulfide-linked αCTs in the activation of insulin-like growth factor 1 receptor and insulin receptor. eLife 11:e81286. https://doi.org/10.7554/eLife.81286 (*Co-corresponding author)
- Park J.#, Li J.#, Mayer J., Ball K., Wu J., Hall C., Accili D., Stowell M.*, Bai XC.*, Choi E.* (2022) Activation of the insulin receptor by an insulin mimetic peptide. Nature Communications. 13, 5594. https://www.nature.com/articles/s41467-022-33274-0.pdf (#Co-first author, *Co-corresponding author)
- Li J., Park J., Mayer J., Webb K., Uchikawa E., Wu J., Liu S., Zhang X., Stowell M.*, Choi E.*, Bai XC.* (2022) Synergistic activation of the insulin receptor via two distinct sites. Nat Struct MolBiol. https://doi.org/10.1038/s41594-022-00750-6 (*Co-corresponding author)
- Hall C. and Choi E. (2021) New Scavenger to fine-tune insulin action in b cells. Cell Metabolism. 33(4): 707-708.
- Hall C., Yu H., and Choi E. (2020) Insulin receptor endocytosis in the pathophysiology of insulin resistance. Exp. Mol. Med. 52, 911-920.
- Li J#., Choi E.#*.,Yu H.*, Bai XC.*(2019)Structural basis of the activation of type 1 insulin-like growth factor receptor. Nat. Commun.10, 4567 (#Co-first author, *Co-corresponding author)
- Uchikawa E.#, Choi E.#*, Shang G., Yu H.*, Bai XC.*(2019)Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex. eLife 8, e48630. (#Co-first author, *Co-corresponding author)
- Choi E., Kikuchi S., Gao H., Brodzik K., Nassour I., Yopp A., Singal A., Zhu H., and Yu H. (2019)Mitotic regulators and the SHP2-MAPK pathway promote insulin receptor endocytosis and feedback regulation of insulin signaling. Nat. Commun. 10, 1473.
- Choi E.and Yu H. (2018)Spindle checkpoint regulators in insulin signaling. Front. Cell Dev. Biol. 6:161.
- Kim J., Hu Z., Cai L., Li K., Choi E., Faubert B., Bezwada D., Rodriguez-Canales J., Villalobos P., Lin YF., Ni M., Huffman K., Girard L., Byers L., Kacmaz K., Pna C., Heymach J., Wauters E., Vansteenkiste J., Castrillon D., Chen B., Wistuba I., Lambrechts D., Xu J., Minna J., and DeBerardinis R. (2017)CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. Nature 546 (7656): 168-72.
- Choi E., Zhang X., Xing C., and Yu H. (2016)Mitotic checkpoint regulators control insulin signaling and metabolic homeostasis. Cell 166 (3): 567-81.
- Choi E. and Yu H. (2015). Phosphorylation propels p31cometfor mitotic exit. Cell Cycle 14 (13) 1997-8.
- Park I., Lee HO., Choi E., Lee Y-K., Kwon M-S., Min J., Park P-G., Lee S., Kong Y-Y., Gong G., and Lee H. (2013). Loss of BubR1 acetylation causes defects in spindle assembly checkpoint signaling and promotes tumor formation. J. Cell Biol. 202 (2): 295-309.
- Choi E*., Park P-G*., Lee HO*., Lee Y-K., Kang GH., Lee JW., Han W., Lee HC., Noh D-Y., Lekomtsev S., Gong GY., and Lee H. (2012). BRCA2 fine-tunes the spindle assembly checkpoint through reinforcement of BubR1 acetylation. Dev. Cell 22:295-308. (*Co-first author)
- Choi E., Choe H., Min J., Choi J-Y., Kim J., and Lee H. (2009). BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing in mitosis. EMBO J. 28: 2077-2089.
- Lee Y., Choi E., Park P-G., Kim M. A., Park N-H, and Lee H. (2009). BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers. Brit. J. Cancer101: 504-510.
- Choi E. and Lee H. (2008). Chromosome damage induces BubR1 activation and prometaphase arrest. FEBS Letters 582:1700-1706.