Group Leader
Research: At MIA-Portugal, the Molecular Ageing, RNA Chemistry & Oncogenesis Group will focus on the physiological roles of the p53 gene and all its RNA and protein products, with particular attention to the processes that affect tissue and cell maintenance, regeneration, transformation and ageing.
Concept: Many diseases from dementia to heart failure, degenerative diseases, cancer and even the natural ageing process, all result from a loss of adequate cell function in specialized tissues. p53 has been associated with all these conditions, but the mechanisms are unclear. In our lab we have observed that different cell types show unique and characteristic p53 product profiles and that manipulating them alters cell behaviour and fate. By investigating the presence, regulation and role of p53 (in all its forms) in different cells, tissues and organs, we want to gain insight on how p53 manages each different cell type. We hope to understand the exact role of the different p53 products and their regulation in specific cells and tissues in order to help protect these cells (and subsequently the organism) from disease, degeneration, transformation and ageing.
Relevant publications:
Shrutee N. Parkar, Maria José López-Iniesta, Ana Catarina Ramalho, Koto Kimura, Jingyuan Zhao, Filipa da Silva Rita, Luísa Romão & Marco M Candeias. Δ246p53 is a new p53 isoform that responds to DNA damage and regulates tumour growth. bioRxiv 2023; doi: https://doi.org/10.1101/2023.04.07.536059.
Maria José López-Iniesta, Rafaela Lacerda, Ana Catarina Ramalho, Shrutee N. Parkar, Ana Marques-Ramos, Bruna Pereira, Lina Miyawaki, Jun Fujita, Roman Hrstka, Luísa Romão & Marco M Candeias. Internal Translation of p53 Oncoproteins During Integrated Stress Response Confers Survival Advantage on Cancer Cells. bioRxiv 2023; doi: https://doi.org/10.1101/2023.03.03.531004.
López-Iniesta, M.J.; Parkar, S.N.; Ramalho, A.C.; Lacerda, R.; Costa, I.F.; Zhao, J.; Romão, L.; & Marco M Candeias. Conserved Double Translation Initiation Site for Δ160p53 Protein Hints at Isoform’s Key Role in Mammalian Physiology. Int. J. Mol. Sci. 2022, 23, 15844.
Pan, M.; Zorbas, C.; Sugaya, M.; Ishiguro, K.; Kato, M.; Nishida, M.; Zhang, H.-F.; Marco M Candeias; Okamoto, A.; Ishikawa, T.; Soga T.; Aburatani H.; Sakai J.; Matsumura Y.; Suzuki T.; Proud C.G.; Lafontaine D.L.J.; Osawa T. Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors. Nat. Commun. 2022, 13, 3706.
Jantrapirom, S.; Koonrungsesomboon, N.; Yoshida, H.; Marco M Candeias; Pruksakorn, D.; Lo Piccolo, L. Long noncoding RNA‐dependent methylation of nonhistone proteins. WIREs RNA 2021, 12.
Lacerda, R.; Menezes, J. & Marco M Candeias. Alternative Mechanisms of mRNA Translation Initiation in Cellular Stress Response and Cancer. In The mRNA Metabolism in Human Disease; Adv Exp Med Biol 2019; pp. 117–132.
Marques-Ramos, A.; Marco M Candeias; Menezes, J.; Lacerda, R.; Willcocks, M.; Teixeira, A.; Locker, N.; Romão, L. Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition. RNA 2017, 23.
Candeias MM, Hagiwara M, Matsuda M. Cancer-specific mutations in p53 induce the translation of Δ160p53 promoting tumorigenesis. EMBO Rep. 2016 Nov;17(11):1542-1551. doi: 10.15252/embr.201541956. Epub 2016 Oct 4. PMID: 27702985; PMCID: PMC5090711.
Gajjar M, Candeias MM, Malbert-Colas L, Mazars A, Fujita J, Olivares-Illana V, Fåhraeus R. The p53 mRNA-Mdm2 interaction controls Mdm2 nuclear trafficking and is required for p53 activation following DNA damage. Cancer Cell. 2012 Jan 17;21(1):25-35. doi: 10.1016/j.ccr.2011.11.016. PMID: 22264786.
Candeias MM, Malbert-Colas L, Powell DJ, Daskalogianni C, Maslon MM, Naski N, Bourougaa K, Calvo F, Fåhraeus R. P53 mRNA controls p53 activity by managing Mdm2 functions. Nat Cell Biol. 2008 Sep;10(9):1098-105. doi: 10.1038/ncb1770. PMID: 19160491.