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Dr Joo-Hyeon Lee

Dr Joo-Hyeon Lee

Group Leader, Stem Cells and Niche Laboratory, The Wellcome Trust – MRC Stem Cell Institute

Sir Henry Dale Wellcome Trust Fellow

Joo-Hyeon Lee is accepting applications for PhD students.


Research Interests

What are the regulatory mechanisms that control homeostatic turnover, and how do their perturbation contribute to disease progression? Lungs are slow turnover organs that are highly quiescent at steady-state. However, the lung has a tremendous ability to repair epithelial damage following injury and contains multiple, highly plastic, stem cell populations. We are interested in understanding how stem cells respond to different signals from their local environment and orchestrate the changes in chromatin, transcription, translation, and cellular dynamics in homeostasis and injury repair. Questions that we are trying to address are: 1) what mechanisms regulate the transition of cells from quiescent to dividing and back again? 2) How do distinct cell types sense different injuries? 3) Which cell populations have the flexibility to de-differentiate and when are these complementary repair mechanisms used? Elucidating the normal process of lung dynamics will provide us a foundation to understand lung diseases and cancer.

We apply ex vivo 3D organoid cultures of human and mouse lungs with genetic tools, in vivo transgenic mouse models with lineage tracing techniques, quantitative mathematic modelling of clonal dynamics, and bioinformatics at the single cell level.

Our keywords include: quiescence, lineage specification, plasticity, reprogramming, heterogeneity, cell-cell competition, niche.

Collaborators        

Jinwook Choi (Research Associate)
Julie Watson (Research Associate)
Catherine Dabrowska (PhD graduate student)
Kelly Evans (PhD graduate student)
Inchul Cho (MPhil student)
Antranik Mavousian (Research assistant)

Teaching

PDN Part II L6/P6 Development course

Key Publications

Lazarus KA, Hadi F, Zambon E, Bach K, Sannolla MF, Watson JK, Correia LL, Das M, Ugur R, Pensa S, Becker L, Campos LS, Ladds G, Liu P, Evans G, McCaughan F, Quesne JL, Lee JH, Calado D, and Khaled WT (2018). BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous cell carcinoma. Nat Com. In press

Lee JH and Rawlins EL (2017). Developmental mechanisms and adult stem cells for therapeutic lung regeneration. Dev Biol. 433(2). Corresponding authors

Lee JH, Tammela T, Hofree M, Choi J, Marjanovic ND, Han S, Canner DA, Wu K, Paschini M, Bhang DH, Jacks T, Regev A, Kim CF (2017). Anatomically and functionally distinct lung mesenchymal populations marked by Lgr5 and Lgr6. Cell. 170(6):1149-1163. Corresponding authors

Choi J, Iich E, Lee JH (2016) Organogenesis of adult lung in a dish: Differentiation, disease and therapy. Dev Biol. 420(2):278-286

Lee JH and Kim CF (2014) Mesenchymal progenitor panoply. Science. 346 (6211):810-1

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.

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

Chen H, Matsumoto K, Brockway BL, Rackley CR, Liang J, Lee JH, Jiang D, Noble PW, Randell SH, Kim CF, Stripp BR (2012) Airway epithelial progenitors are region specific and show differential responses to bleomycin-induced lung injury. Stem Cells. 30(9):1948-60

Tropea KA, Leder E, Aslam M, Lau AN, Raiser DM, Lee JH, Balasubramaniam V, Fredenburgh LE, Mitsialis SA, Kourembanas S, Kim CF (2012) Bronchioalveolar stem cells increase after mesenchymal stromal cell treatment in a mouse model of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol. 302(9):L829-37

Zacharek SJ, Fillmore CM, Lau AN, Gludish DW, Chou A, Ho JW, Zamponi R, Gazit R, Bock C, Jäger N, Smith ZD, Kim TM, Saunders AH, Wong J, Lee JH, Roach RR, Rossi DJ, Meissner A, Gimelbrant AA, Park PJ, Kim CF (2011) Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci. Cell Stem Cell. 9:272-81

Lee KP*, Lee JH*, Kim TS, Park HD, Byun JS, Kim MC, Jeong WI, Calvisi DF, Kim JM and Lim DS (2010) The Hippo–Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. PNAS. 107:8248-53. *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

Above: Lung organoids retaining alveolar lineages

Above: Ex vivo lung organoids

Above: Mouse lung alveoli