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 research focuses on determining how microenvironments affect tumour progression and radiation responses. We are specifically interested in MAFF, a bZIP transcription factor, which plays a significant role in antioxidant responses. While RT induces cell killing by direct DNA damage, approximately two-thirds of radiation damage is induced indirectly through increased production of reactive oxygen species (ROS). In addition to their role in DNA damage, ROS regulate signal transduction and redox pathways to promote tumour cell survival and expansion. To increase the efficacy of RT in killing tumour cells, we need to manipulate the redox environment of cancer cells focusing on ROS-sensing signalling pathways.

MAFF, which lacks a transactivation domain, is an essential binding partner of well-known regulators of antioxidant responses such as NRF2 and BACH1. In our recent study, we demonstrated that MAFF promotes tumour cell invasion and metastasis both in vitro and in vivo using breast cancer models. Through RNA- and ChIP-sequencing, we identified IL11 as a direct transcriptional target of MAFF that mediates the invasive and metastatic behaviour of tumour cells. Since breast cancers express low levels of NRF2, which is a well-known binding partner of MAFF that regulates cellular antioxidant responses, we used mass spectrometry to determine MAFF binding partners and found that BACH1 was the most abundant MAFF binding partner of MAFF in our breast cancer models. Expanding this study to ovarian and lung cancer models, we also confirmed that MAFF enhances tumour invasion and metastasis, indicating its important role in a variety of tumour types.

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

We further expand our studies to evaluate the role of MAFF in the crosstalk with tumour microenvironment which impacts tumour metastasis and treatment responses.