Academic Spotlight: Professor Joo-Hyeon Lee

Joo-Hyeon Lee
Associate Professor, Wellcome Senior Research Fellow

Wellcome – MRC Cambridge Stem Cell Institute, Department of PDN, University of Cambridge

Research focus:
We are interested in understanding the mechanisms of stem cell fate regulation. We particularly investigate how stem cells sense environmental changes and determine their cell fate, and how niches develop and remodel the local environment during lung homeostasis, regeneration and the early stages of disease progression utilising combined in vitro organoids, in vivo genetic mouse models, single cell multi-omics, and clonal biophysical modelling.

Recent advance from the lab:
While the acquisition of cellular plasticity is essential for tissue regeneration after injury, the precise cellular events and molecular mechanisms that direct stem cell fate behaviours remain elusive in part due to the complexity of lung architecture and cellular composition. We recently demonstrated cellular and molecular programmes that regulate lung stem cell differentiation that is directed by inflammatory niches during lung regeneration after injury, and their relevance in lung diseases (Choi et al. Cell Stem Cell. 2020; Choi et al. Nat Cell Biol. 2021; Jeon et al. EMBO J. 2022). We developed in vitro 3D human lung organoid models and established their single cell atlas to understand human lung regeneration and diseases, including SARS-CoV-2 infection (Youk et al. Cell Stem Cell. 2020; Lee et al. EMM. 2023), in addition to creating macroscale in vitro airway tubes with air-perfusion function (Liu et al. Adv. Science. 2021).

Key challenge for the field:
Despite the fact that mouse and human lung cells are largely conserved, recent single cell technologies enabled us to identify previously unrecognised cell types and states in human lungs. These cell populations are often heterogeneous, with transient states enriched in the lungs of lung disease patients. Human lung ex vivo organoid models are actively being developed, yet many challenges remain, including a lack of mature differentiated cells. To overcome these challenges, concerted efforts from numerous groups, including ours, are being made to create tissue-scale in vitro models replicating native lung tissues. These multidisciplinary approaches will enable us to identify healthy and disease-associated human lung cell states, establish integrated disease models, and, eventually, develop therapeutics for lung diseases.

Most exciting basic or clinical breakthrough in the past few years:
Epithelial plasticity is an intriguing phenomena that underpins cellular behaviour in embryonic development, tissue regeneration, and cancer across most tissues. Over the past few years, our group has discovered previously unseen damage-associated cellular states that emerge during regeneration, which has significant implications for human lung diseases. We are currently investigating how the regenerative response of epithelial cells transitions to pathological remodelling, which could lead to new treatment targets for lung diseases.