EPITRANSCRIPTOMICS in CANCER BIOLOGY

An increasing body of evidence indicates that translation reprogramming plays key roles in cancer development and drug resistance but the mechanisms involved in this process remain poorly understood. Specific tRNA modifications are required to optimize translation. In our lab, we hypothesize that such modifications may contribute to protein synthesis rewiring during tumorigenesis (1). We recently uncovered the key importance of codon-specific translation reprogramming in cancer development and drug resistance (2-3). By using a combination of mouse models of cancer, unbiased proteomics, single cell sequencing, ribosome profiling approaches, functional analysis with patient derived materials, and a deep molecular dissection of cellular signaling pathways, our work aims at providing a comprehensive examination of the contribution of specific tRNA modifications in oncogenic transformation, metastasis formation and drug resistance, with a particular emphasis in tumor immunology. Together, we hope to uncover new general mechanisms that support tumor adaptation through regulation of specific protein synthesis and will help define new therapeutic opportunities to fight cancer. 

Selected publications:

Close et al, Mol Cell (2006)

Close et al, Cell. Mol. Life Sc. (2010)               

Close et al, J. Biol. Chem. (2012)

Close et al, Nature (2012)

Ladang, Rapino et al, J.Exp.Med. (2015)

Delaunay et al, J.Exp.Med. (2016)

(1)Rapino et al, Trends in Cancer (2017)

(2)Rapino et al, Nature (2018)

(3)Rapino et al, Nature Comm. (2021)

Funding category: Contrat doctoral

Bourse de doctorat de 4 ans

PHD title: Doctorat en Sciences Biomédicales et Pharmaceutiques

PHD Country: Belgique