MOON GROUP

GROUP INFORMATION

We are young and productive research group with our passion in science. We hope that our collaborative and interdisciplinary culture will lead us to be a bridge from the bench to the bedside. We are highly skilled and well equipped as a part of Department of Oncology at University of Oxford. We also appreciate the importance of scientific thought processes and critical analysis to support our trainees to become independent researchers. Our study equally emphasises works in vitro, in vivo, and in patient settings. Basic molecular and biochemical work will be empowered by global analysis using sequencing and mass spectrometry. Using mouse models and patient samples (i.e. tissue microarray), we deliver our studies into preclinical setting as well. 

RESEARCH SUMMARY

Our laboratory investigates the intricate relationship between the tumour microenvironment, cancer progression, and responses to therapy. A primary focus of our work is to understand and overcome tumour metastasis, the principal cause of cancer-related death. We aim to identify the fundamental mechanisms that allow cancer cells to adapt to stress, resist treatment, and spread to distant organs, and to translate these discoveries into innovative therapeutic strategies.

Our research is built on several interconnected pillars:

1. Unravelling the Molecular Drivers of Metastasis

We seek to identify the key molecular switches that enable cancer cells to become invasive and metastatic, with the goal of developing novel targeted therapies. Our approach involves identifying critical nodes in pro-metastatic signalling pathways and validating them as therapeutic targets in clinically relevant models.

For example, our group has established the transcription factor MAFF as a master regulator of tumour aggressiveness (Moon et al., Nature Comm, 2021). We have shown that MAFF drives a pro-metastatic programme across multiple cancer types, including breast, ovarian, and lung cancer. Mechanistically, we identified Interleukin-11 (IL11) as a key downstream target of this axis, revealing a direct link between a core cellular stress response pathway and the acquisition of invasive and therapy-resistant cancer phenotypes.

In breast cancer patient tissues, MAFF expression (brown staining) is detected, and its intensity increases in more metastatic and aggressive tumours.

Figure 1. MAFF expression in primary and metastatic breast cancer tissues (Moon et al. Nature Comm, 2021)

Expanding our search for such critical drivers, our research has also identified the receptor tyrosine kinase AXL as a key therapeutic target in bile duct cancer (cholangiocarcinoma), a cancer with very limited treatment options and a poor prognosis (Kim et al., Cancers, 2023). We demonstrated that high levels of AXL correlate with metastasis and poor patient outcomes. Crucially, we showed that inhibiting AXL's activity using both genetic approaches and a novel decoy receptor (AVB-500) potently blocks tumour growth and dissemination in preclinical models. This work validates AXL as a highly promising target for a difficult-to-treat malignancy and underscores our commitment to tackling cancers with urgent unmet needs.  

Figure 2. Graphical representation of AXL inhibitor suppressing bile duct cancer progression (Kim et al. Cancers. 2023).

2. Novel Mechanisms of FLASH radiation

Alongside targeting the intrinsic drivers of metastasis, we work with advanced therapeutic modalities to make them safer and more effective. In collaboration with Petersson group, our lab is investigating FLASH radiotherapy (FLASH-RT), a revolutionary technique that delivers radiation at an ultra-high dose rate. This produces the remarkable "FLASH effect": it spares healthy normal tissues from damage while maintaining equivalent anti-tumour efficacy.

While the clinical potential is immense, the underlying biological mechanism has remained a mystery. In a recent landmark paper (Vilaplana-Lopera et al., Cell Death & Disease, 2025), we provided a key piece of this puzzle. We discovered that the FLASH effect is driven by intrinsic differences in iron metabolism between normal and cancerous tissues. Cancer cells are "iron-addicted," making them uniquely vulnerable to ferroptosis, an iron-dependent form of cell death, induced by FLASH-RT. In contrast, normal tissues have lower baseline iron levels and are spared from this cascade of lipid peroxidation. We proved this by feeding mice a high-iron diet, which elevated iron levels in normal tissues and completely abolished the protective FLASH effect, making them as sensitive to radiation as the tumours. This work provides a novel, metabolism-based explanation for one of the most exciting advances in radiotherapy.   

Figure 3. The impact of iron and ferroptosis on the differential FLASH response in normal and tumor tissues (Vilaplana Lopera et al. Cell Death and Disease, 2025).

Our Vision: A Unified Approach to Targeting Cancer Vulnerabilities

Our research programme is uniquely positioned at the intersection of metastasis research and radiation biology. By understanding how a cell's intrinsic stress-response programming dictates its fate when challenged with an extrinsic therapeutic approaches, we can uncover new vulnerabilities and design more rational, effective combination therapies.  

Our work combines cutting-edge molecular biology, genomics (RNA- and ChIP-seq), lipidomics, and sophisticated in vivo cancer models to dissect these complex mechanisms. The ultimate goal of our laboratory is to translate these fundamental insights into novel strategies that overcome therapeutic resistance and improve outcomes for cancer patients.