Lymphatic vasculature regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood circulation. Defects in lymphatic vasculature can cause lymphedema, which is characterized by the swelling of hands or legs. Currently there is no cure for lymphedema. The other diseases caused by defective lymphatic vasculature include obesity, fibrosis, high blood pressure and angiosarcoma. I am interested in understanding the roles of signaling pathways that regulate lymphatic vascular development. Wnt/β-catenin signaling is an evolutionarily conserved signaling pathway that plays pivotal roles in embryonic development and in adult homeostasis. I recently discovered that Wnt/b-catenin signaling is critical for the development of the lymphatic vasculature. Mice lacking β-catenin have defective lymphatic vessels that lack valves. We identified human lymphedema-associated transcription factor FOXC2 as a target of Wnt/b-catenin signaling. These new insights suggested that Wnt/β-catenin signaling could be a novel target for treating lymphedema. I am interested in screening already available drugs that could enhance Wnt/b-catenin to determine whether they could be used to treat lymphedema in mouse models. In addition, I am dissecting Wnt/b-catenin signaling pathway to identify novel regulators and additional targets for clinical intervention.
B.S., Department of Life Science, University of Seoul, Korea, 2006
M.S., Department of Life Science, University of Seoul, Korea, 2008
Ph.D., Department of Life Science, University of Seoul, Korea, 2013
Postdoctoral Fellow, Oklahoma Medical Research Foundation, Oklahoma City, USA, 2013 - 2017
Joined OMRF's Scientific Staff in 2017
Mahamud MR, Geng X, Ho YC, Cha B, Kim Y, Ma J, Chen L, Myers G, Camper S, Mustacich D, Witte M, Choi D, Hong YK, Chen H, Varshney G, Engel JD, Wang S, Kim TH, Lim KC, Srinivasan RS. GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis through miR-126. Development, 2019 October, PMID: 31582413
Kim W, Khan SK, Liu Y, Xu R, Park O, He Y, Cha B, Gao B, Yang Y. Hepatic Hippo signaling inhibits protumoural microenvironment to suppress hepatocellular carcinoma. Gut 67:1692-1703, 2018 September, PMID: 28866620, PMCID: PMC6592016
Choi D, Park E, Jung E, Cha B, Lee S, Yu J, Kim PM, Lee S, Hong YJ, Koh CJ, Cho CW, Wu Y, Li Jeon N, Wong AK, Shin L, Kumar SR, Bermejo-Moreno I, Srinivasan RS, Cho IT, Hong YK. Piezo1 incorporates mechanical force signals into the genetic program that governs lymphatic valve development and maintenance. JCI Insight 4, 2019 March, PMID: 30676326, PMCID: PMC6483520
Cho SJ, Cha BS, Kwon OS, Lim J, Shin DM, Han DW, Ishitani T, Jho EH, Fornace AJ, Cha HJ. Wip1 directly dephosphorylates NLK and increases Wnt activity during germ cell development. Biochim Biophys Acta. 2017 Feb 6.
Cha B, Srinivasan RS. Mechanosensitive β-catenin signaling regulates lymphatic vascular development. BMB Rep. 2016 Aug;49(8):403-4.
Cha B, Geng X, Mahamud MR, Fu J, Mukherjee A, Kim Y, Jho EH, Kim TH, Kahn ML, Xia L, Dixon JB, Chen H, Srinivasan RS. Mechanotransduction activates canonical Wnt/β-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves. Genes Dev. 2016 Jun 15;30(12):1454-69. doi: 10. 1101/gad.282400.116. Epub 2016 Jun 16. (Cover Article)
Cha B*, Park Y*, Hwang BN, Kim SY, Jho EH. Protein Arginine Methyltransferase 1 Methylates Smurf2. Mol Cells. 2015 Aug;38(8):723-8. doi: 10.14348/molcells.2015.0113. Epub 2015 Jul 1. (*co-first author)
Cha B*, Kim W*, Kim YK, Hwang BN, Park SY, Yoon JW, Park WS, Cho JW, Bedford MT, Jho EH. Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling. Oncogene. 2011 May 19;30(20):2379-89. doi: 10.1038/onc.2010.610. Epub 2011 Jan 17. (*co-first author)
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