Professor Xin Lu

Background

Professor Lu is the Director of the Ludwig Institute for Cancer Research (LICR), Oxford Branch, co-Director of the Cancer Research UK Oxford Centre, NIHR Oxford Biomedical Research Centre Multi-Modal Cancer Therapies Theme Lead and Director of the Oxford Centre for Early Cancer Detection. She is a Fellow of the Royal Society, the Academy of Medical Sciences and the Royal Society of Biology, a Fellow by election of the Royal College of Pathologists, and a Member of the European Molecular Biology Organisation. Following her MSc in China, she received a research training fellowship from WHO and moved to the UK in 1986. She completed her PhD and postdoctoral training, and established her own research group at the LICR in 1993. She became the Director of the LICR’s London Branch in 2004 and in 2007 she established LICR Oxford. She was elected supernumerary fellow at Magdalen College in 2013.

Research

Professor Lu’s group has long-standing research interests in tumour suppression. She was one of the first researchers to show that the tumour suppressor p53 responds to both oncogene activation and DNA damaging signals. Her group was one of the first to demonstrate how to selectively activate p53 to kill cancer cells, through identification and characterization of the evolutionarily conserved ASPP family of proteins. In addition to cancer, the ASPPs have now been implicated in the pathogenesis of other disorders, including sudden cardiac death and brain abnormalities.

The main goal of her research is to identify molecular mechanisms that control cellular plasticity and suppress tumour growth. Cells are able to change their characteristics and cell fate in response to external signals. This ability to change – cellular plasticity – underlies cancer initiation, metastasis and resistance to therapy. The group are particularly interested in ‘guardians’ of plasticity in epithelial cells, from which over 80% of human tumours originate. In particular, they are interested in understanding how selective transcription controls cell fate; identifying regulators of cellular plasticity in upper gastrointestinal cancer initiation and metastasis (particularly oesophageal cancer and gastric cancer); and understanding the influence of infection on cell plasticity and cancer (particularly Helicobacter pylori and Epstein Barr Virus (EBV) infection).

Selected Publications

• Ma, J., Al Moussawi, K., Lou, H., Chan, H.F., Wang, Y., Chadwick, J., Phetsouphanh, C., Slee, E.A., Zhong, S., Leissing, T.M., Roth, A., Qin, X., Chen, S., Yin, J., Ratnayaka, I., Hu, Y., Louphrasitthiphol, P., Taylor, L., Bettencourt, P.J.G., Muers, M., Greaves, D.R., McShane, H., Goldin, R., Soilleux, E.J., Coleman, M.L., Ratcliffe, P.J. and Lu, X. (2024) ‘Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment’, Proc Natl Acad Sci USA, 121(10), p. e2309957121.
• Carroll, T.M., Chadwick, J.A., Owen, R.P., White, M.J., Kaplinsky, J., Peneva, I., Frangou, A., Xie, P.F., Chang, J., Roth, A., Amess, B., James, S.A., Rei, M., Fuchs, H.S., McCann, K.J., Omiyale, A.O., Jacobs, B.-A., Lord, S.R., Norris-Bulpitt, S., Dobbie, S.T., Griffiths, L., Ramirez, K.A., Ricciardi, T., Macri, M.J., Ryan, A., Venhaus, R.R., Van Den Eynde, B.J., Karydis, I., Schuster-Böckler, B., Middleton, M.R. and Lu, X for the LUD2015-005 Project Team.(2023) ‘Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma’, Cancer Cell, 41(7), pp. 1222-1241.
• Al Moussawi, K., Chung, K., Carroll, T.M., Osterburg, C., Smirnov, A., Lotz, R., Miller, P., Dedeić, Z., Zhong, S., Oti, M., Kouwenhoven, E.N., Asher, R., Goldin, R., Tellier, M., Murphy, S., Zhou, H., Dötsch, V. and Lu, X. (2022) ‘Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis’, Cell Reports, 41(3), p. 111503.
• Chen, S., Wu, J.-L., Liang, Y., Tang, Y.-G., Song, H.-X., Wu, L.-L., Xing, Y.-F., Yan, N., Li, Y.-T., Wang, Z.-Y., Xiao, S.-J., Lu, X., Chen, S.-J. and Lu, M. (2021) ‘Arsenic trioxide rescues structural p53 mutations through a cryptic allosteric site’, Cancer Cell, 39(2), pp. 225-239.e8.
• Chen S, Wu J, Zhong S, Li Y, Zhang P, Ma J, Ren J, Tan Y, Wang Y4 Au KF, Siebold C, Bond GL, Chen Z, Lu M, Jones EY, Lu X (2019). iASPP mediates p53 selectivity through a modular mechanism fine-tuning DNA recognition. Proc Natl Acad Sci USA 116 (35) 17470-17479.
• Owen RP, White MJ, Severson DT, Braden B, Bailey A, Goldin R, Wang LM, Ruiz-Puig C, Maynard ND, Green A, Piazza P, Buck D, Middleton MR, Ponting CP, Schuster-Böckler B, Lu X (2018). Single cell RNA-seq reveals profound transcriptional similarity between Barrett’s oesophagus and oesophageal submucosal glands. Nature Commun 9, 4261
• Lu M, Breyssens H, Salter V, Zhong S, Hu Y, Baer C, Ratnayaka I, Sullivan A, Brown NR, Endicott J, Knapp S, Kessler BM, Middleton MR, Siebold C, Jones EY, Sviderskaya EV, Cebon J, John T, Caballero OL, Goding C, Lu X (2016). Restoring p53 Function in Human Melanoma Cells by Inhibiting MDM2 and Cyclin B1/CDK1-Phosphorylated Nuclear iASPP. Cancer Cell 30, 822-823.
• Notari M, Hu Y, Sutendra G, Dedeić Z, Lu M, Dupays L, Yavari A, Carr CA, Zhong S, Opel A, Tinker A, Clarke K, Watkins H, Ferguson DJP, Kelsell DP, de Noronha S, Sheppard MN, Hollinshead M, Mohun TJ, Lu X (2015). iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death. Proc Natl Acad Sci USA. 112(9):E973 – E981
• Wang Y, Bu F, Royer C, Serres S, Larkin JR, Soto MS, Sibson NR, Salter V, Fritzsche F, Turnquist C, Koch S, Zak J, Zhong S, Wu G, Liang A, Olofsen PA, Moch H, Hancock DC, Downward J, Goldin RD, Zhao J, Tong X, Guo Y, Lu X (2014). ASPP2 controls epithelial plasticity and inhibits metastasis through β-catenin-dependent regulation of ZEB1. Nature Cell Biol 16, 1092-1104
• Lu M, Zak J, Chen S, Sanchez-Pulido L, Severson DT, Endicott J, Ponting CP, Schofield CJ, Lu X (2014). A Code for RanGDP Binding in Ankyrin Repeats Defines a Nuclear Import Pathway. Cell 157(5):1130-1145
• Bergamaschi D, Samuels-Lev Y, O’Neil NJ, Trigiante G, Crook T, Hseih JK, O’Connor DJ, Zhong S. Campargue I, Tomlinson ML, Kuwabara PE, Lu X (2003). iASPP oncoprotein is a key inhibitor of p53 conserved from worms to humans. Nat Genet 33(2):162-7.
• Samuels-Lev Y, O’Conner DJ, Bergamaschi D, Trigiante G, Hsieh JK, Zhong S, Campargue I, Naumovski L, Crook T, Lu X (2001). ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell 8(4):781-94.