The role of MAFF-mediated redox system in tumour and immune responses
Cancer treatments including radiation and chemotherapy exert the anti-cancer effect through the production of reactive oxygen species (ROS). However, cancer cells find a way to evade cell death through the adaptation of redox pathways, which results in tumour progression and treatment resistance. It is critical to determine the signals and key genetic pathways in the regulation of adaptive redox pathways of tumour cells.
This project will run based on the close collaboration of Moon and Olcina labs. Students are expected to have intensive trainings from both investigators while acquiring essential skills in molecular biology and in vivo studies. Students will also perform screenings using sequencing and mass spectrometry analysis. During the DPhil programme, students will learn scientific thought processes by setting up hypothesis, performing experiments, and analysing data, which will prepare them to become an independent researcher.
Group Leader in Radiation Biology and the Tumour Microenvironment
In Moon lab, we focus on determining how hypoxia promotes tumour progression such as invasion, metastasis, and metabolism through key pathways involving MAFF protein.
The regulation of MAFF protein, a family of transcription factors, has been implicated in the transactivation of antioxidant response genes. Our work demonstrated that the level of small MAFF protein expression is critical to the regulation of gene induction or repression, indicating that stresses like hypoxia act like a rheostat in regard to the formation of MAFF homodimer and heterodimer formation, leading to transactivation or gene repression. Biologically, we found that the MAFF protein is a major regulator of tumour cell invasion and metastasis under hypoxia, and impact the radiation response of cells though controlling antioxidant gene transcription. Moon lab will focus on how MAFF itself, or along with its binding proteins, interplays to alter tumour metabolism and radiation damage under hypoxic conditions.
Dr. Moon received her PhD degree from Duke University, USA. She was trained by Dr. Mark W. Dewhirst to focus on the effect of hypoxia-inducible factor (HIF) on tumour reoxygenation after mild hyperthermia. During the training, she was awarded a predoctoral fellowship from Breast Cancer Research Program (BCRP) of Department of Defense (DoD), USA. Then she joined Dr. Amato Giaccia’s lab at Stanford University, USA, to study hypoxia regulation of MAFF protein and its role in tumour cell invasion and radiation responses. Her current research interests are radiation responses and metabolic changes under hypoxia.
Nuria Vilaplana Lopera, PhD, Postdoctoral Researcher
Maria Jerome, MRes student
Jiyoung Kim, Research Assistant
MRC RESEARCH PROGRAMME:
MAFF-mediated transcription regulation of redox pathways in response to radiation treatment
Manassantin A inhibits tumour growth under hypoxia through the activation of chaperone-mediated autophagy by modulating Hsp90 activity
Byun J-K. et al, (2023), British Journal of Cancer
Ferroptosis, a key to unravel the enigma of the FLASH effect?
Vilaplana-Lopera N. et al, (2022), Br J Radiol
ACSL3 regulates lipid droplet biogenesis and ferroptosis sensitivity in clear cell renal cell carcinoma.
Klasson TD. et al, (2022), Cancer Metab, 10
Targeting Hypoxia: Revival of Old Remedies
Vilaplana-Lopera N. et al, (2021), Biomolecules, 11, 1604 - 1604
The importance of hypoxia in radiotherapy for the immune response, metastatic potential and FLASH-RT
OLCINA DEL MOLINO M. et al, (2021), International Journal of Radiation Biology