Dr Joo-Hyeon Lee
Stem cells and niches
Cambridge Stem Cell Institute, Gleeson Building
In the lung, multiple stem/progenitor cells that reside in a distinct niche regenerate the lost epithelium upon tissue injury, yet it is unknown how stem cells are instructed to selectively replace the injured epithelial cells. Our lab focuses on identifying the key stem-stromal cell interactions and regulatory networks that allow proper lineage specification and tissue regeneration. Dissecting the precise mechanisms how niches develop and remodel in homeostasis, regeneration and injury repair will help us to find better ways to derive lineage differentiation of stem cells, establish stem cell transplantation methods, and eventually lead us to novel insights on the pathogenesis of lung diseases.
Our goals include:
1) Identifying the functional role of diverse pulmonary stromal cells in regulating stem cell lineage differentiation during lung homeostasis, regeneration and injury repair.
2) Defining the regulatory networks of stem cell and stroma interactions in lung regeneration and tumourigenesis.
3) Exploring the contribution of stem cell niche dysregulation in pulmonary pathogenesis. We will use systemic approaches combining in vivo genetic mouse models and ex vivo human and mouse lung organoid co-culture systems.
Our research focuses on the regulation of the environment in which lung stem cells reside along with pulmonary axis. Lung stem cells require tight control to allow the production and differentiation of new cells to replace damaged cells by interacting with neighbouring cells. Uncontrolled interactions can cause lung disease including lung cancer. Therefore, understanding these essential interactions is crucial to improve our basic knowledge of pulmonary biology and disease. We will identify the functional complex of environment including key neighbouring cells and molecules that regulate lung stem cell differentiation in health and disease, making it possible to find new therapeutic avenues for lung disease.
- Lee JH, Kim CF (2014) Mesenchymal progenitor panoply. Science. 346 (6211):810-1 (perspectives). PMID:25395521
- Lee JH, Bhang DH, Beede A, Huang TL, Stripp B, Bloch KD, Wagers AJ, Tseng YH, Ryeom S, Kim CF (2014) Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1- Thrombospondin-1 axis. Cell. 156(3):440-55. PMCID:PMC3951122
- Lee JH, Kim J, Gludish D, Roach RR, Saunders AH, Barrios J, Woo AJ, Chen H, Conner DA, Fujiwara Y, Stripp B, Kim CF (2013) Surfactant protein-C chromatin-bound green fluorescence protein reporter mice reveal heterogeneity of surfactant protein C-expressing lung cells. Am J Respir Cell Mol Biol. 48(3):288-98. PMCID:PMC3604082
- Lee KP*, Lee JH*, Kim TS, Park HD, Byun JS, Kim MC, Jeong WI, Calvisi DF, Kim JM, Lim DS (2010) The Hippo–Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. PNAS. 107:8248-53. PMCID:PMC2889558 (*Equal contribution)
- Lee JH, Kim TS, Yang TH, Koo BK, Oh SP, Lee KP, Oh HJ, Lee SH, Kong YY, Kim JM, and Lim DS (2008) A crucial role of WW45 in developing epithelial tissues in the mouse. EMBO J. 27:1231-42. PMCID:PMC2367404
- Lee JH, Lim DS (2006) Dual role of Nbs1 in the ataxia telangiectasia mutated-dependent DNA damage response. FEBS J.273:1630-6. (Review) PMID:16623700
- Lee JH, Xu B, Lee CH, Ahn JY, Song MS, Lee H, Canman CE, Lee JS, Kastan MB, Lim DS (2003) Distinct functions of Nijmegen breakage syndrome in ataxia telangiectasia mutated-dependent responses to DNA damage. Mol Cancer Res. 1:674-81. PMID:12861053