Dr Sally Yunsun Kim is a Lecturer in Respiratory Drug Delivery at the Institute of Pharmaceutical Science, King’s College London. Dr Kim has recently established her lab focused on innovative regenerative medicine approaches to drive lung tissue repair, utilising her expertise in extracellular vesicles, pharmaceutical science and ex-vivo lung tissue slice models.
Dr Kim trained as a pharmacist and had nine years of experience working as a pharmacist in Australia. She completed her MPhil and PhD at The University of Sydney, focused on developing inhalable formulations and aerosolization of mesenchymal stromal cells for targeted delivery to the lungs. In 2018, she joined Dr Charlotte Dean’s laboratory at the National Heart and Lung Institute, Imperial College London, upon the award of the European Respiratory Society / European Molecular Biology Society (EMBO) Long Term Research Fellowship. Dr Kim has been awarded several prestigious fellowships and grants, including the Wellcome Trust Institutional Strategic Support Fund Springboard Fellowship. Through these, she developed a novel approach to study lung injury and repair using precision-cut lung slices and has validated the efficacy of Wnt5a as a potential pro-repair pharmacological factor.
Developing a novel approach to enable targeted drug delivery to injured lung tissue
The clinical translation of novel therapeutics for complex lung diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis is hindered by a lack of good pre-clinical models that recapitulate the complexity of the disease. The proposed work is aimed at establishing a novel approach to deliver a potential therapeutic that targets the extracellular matrix (ECM) in diseased ex-vivo precision-cut lung slices (PCLS).
A critical component in the pathogenesis of COPD and pulmonary fibrosis is dysregulated transforming growth factor-β1 (TGF-β1) signalling [Burgess et al. Am J Respir Cell Mol Biol 2024; 70(4):239]. Increased TGF-β1 signalling is associated with increased ECM production and enhanced fibrotic airway remodelling which impacts lung function. Therefore, pharmacologically targeting the aberrant ECM and airway remodelling by using a TGF-β1 inhibitor, is a promising approach for the treatment of pulmonary fibrosis and COPD, which is not achieved by current therapies.
TGF-β1 receptor inhibitors have been shown to be well tolerated and effective in clinical trials, including galunisertib in phase Ib/II studies for non-small cell lung cancer patients [Nadal et al. BMC Cancer 2023; 23:708]. However, TGF-β1 has a wide range of biological functions, therefore it is critical to develop a targeted delivery platform to specific cell populations and validate its targeting ability within a system where dynamic ECM and heterogeneity of lung cells co-exist.
In this project, the safety and efficacy of TGF-β1 receptor inhibitors, encapsulated in drug delivery vehicles, will be investigated using a PCLS model. PCLS are an ideal clinically relevant ex-vivo model as it retains the complex ECM with intact alveoli and airways consisting of the different cell populations present in their natural in-vivo orientation [Kim et al. Biomaterials 2021; 267:120480]. The outcomes of this project are likely to further expand the use of PCLS models in pharmaceutical science research.
I have recently (2024) joined the Institute of Pharmaceutical Science, King’s College London as a Lecturer in Respiratory Drug Delivery and am establishing my research. My laboratory is focused on delivering innovative pharmacological approaches to drive lung tissue repair, harnessing my interdisciplinary expertise in pharmaceutical science, extracellular vesicles and ex-vivo lung tissue slice models.
I am passionate about developing human ex-vivo precision-cut lung slices (PCLS) as a platform to accelerate clinical translation of novel respiratory drug targets. I have worked with PCLS models since 2018 and as I establish my own lab, I wish to further advance the model which is increasingly used to investigate safety and efficacy of novel therapeutics. Despite the obvious advantages of the PCLS model over other in-vitro models, it needs further validations to test inhalable formulations. The DDL Career Development Award will support me to address this gap and promote the use of this excellent yet underutilised ex-vivo platform in the pulmonary drug delivery field.
More specifically, I will investigate the extent to which the targeted delivery of TGF-β1 receptor inhibitors delivered by spraying alleviates the diseased ECM. The DDL Career Development Award will enable me to establish collaborations with experts in ECM and preclinical models through a laboratory visit to acquire new skill sets as well as robust preliminary data that will support writing strong grant applications for new investigator awards.