The role of MAFF-mediated redox system in tumour and immune responses
Primary Supervisor: Dr Eui Jung Moon
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. Recently. we found that V-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) plays a significant role in tumour progression by modulating ROS production. Based on our RNA sequencing and ChIP sequencing data, we found the key connection between MAFF and complement pathways. Recent studies by Olcina, Moon et al. revealed that the complement system and more, specifically C5AR1 is significantly involved in radiation responses. Therefore, through investigation of the crosstalk between MAFF and the complement system, we will interrogate the role redox system in tumour and immune responses. By doing so, we identify ways to enhance therapeutic responses while identifying novel targets in cancer treatment.
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. Additionally, through weekly lab meetings and departmental seminars, students will be trained to develop skills for presentation, data management, and scientific writing.
Moon, E.J., Mello, S.S., Li, C.G., Chi, J.T., Thakkar, K., Kirkland, J.G., Lagory, E.L., Lee, I.J., Diep, A.N., Miao, Y. and Rafat, M., 2021. The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling. Nature communications, 12(1), pp.1-18.
Olcina, M.M., Stavros, M., Nambiar, D.K., Kim, R.K., Casey, K.M., Woodruff, T.M., Graves, E.G., Quynh-Thu, L., Manuel, S. and Giaccia, A.J., 2020. Targeting C5aR1 increases the therapeutic window of radiotherapy. bioRxiv.