Aura Carreira MorenoStress génotoxique et cancer - CNRS / Institut Curie / Université Paris Saclay
Mes recherches
My career has focused on the study of the structure-functional aspects of biomedically relevant proteins. In particular, I have successively combined biochemistry with other disciplines such as molecular biology, biophysics, cell biology, virology and structural biology either in the study of large multimeric complex proteins using viruses as models (PhD in the lab of M.Garcia Mateu), or studying the proteins involved in the DNA repair process and its link to cancer (Postdoc). In 2006, I got a Postdoctoral Fellowship to study human homologous recombination proteins RAD51 and BRCA2 in the lab of S.C. Kowalczykowski at University of California, Davis (US). There, I contributed to the first biochemical characterization of full-length BRCA2 protein and its mediator activity in DNA repair by homologous recombination.
As an ATIP-AVENIR young investigator (2012) and head the "Homologous Recombination and Cancer" group at Institut Curie, Orsay (FR) we aim to understand the link between BRCA2 mutation and tumorigenesis. We investigate the functions of BRCA2 using a combination of proteomics, biochemistry, and the phenotypic information of missense variants of unknown clinical significance (VUS) identified in breast cancer patients. Which of the functions of BRCA2, when defective, drive tumor formation and whether cells carrying a mono-allelic mutation in BRCA2 display a specific signature are long-standing questions that we are investigating.
Mon projet ATIP-Avenir
Dissecting the role of BRCA2 in the DNA damage response and exploiting its parts for anticancer therapy
Mutations in the tumor suppressor gene, BRCA2, cause susceptibility to breast and ovarian cancer. BRCA2, encodes a protein of 3,418 amino acids required for homologous recombinational DNA repair (HRR), the predominant mechanism employed by cells to accurately repair DNA double-stranded breaks (DSBs). In humans, the central player of the DSBs repair process is RAD51. Through its interaction with RAD51, BRCA2 controls RAD51 function by locating it to the DSBs and allowing its association with ssDNA, the first step on the DNA repair process. In addition, BRCA2 can associate with other proteins and participate in related processes such as cell cycle control or meiotic HR. As a consequence, a defect in this protein leads to uncontrolled cell replication, and genomic instability, both hallmarks of tumor formation. As an independent researcher, my main goals are to dissect the function of human BRCA2 in the context of DNA repair by looking at the evolutionary conservation of domains and, exploit some of these regions for anticancer therapy. My aims are: 1) reveal unknown functions of BRCA2 by mapping the interactions with other proteins involved in DNA repair or related pathways. 2) Better understand the HRR process. 3) Exploit regions of the protein as a therapeutic tool for tumor treatment. 4) Explore a new way to use autonomous parvovirus (innocuous to humans and oncotropic) as vectors to carry these regions to the targeted tumor cells. The combination of basic science (aims 1, 2) and applied science (aims 3, 4) approaches proposed here provides a framework to understand the different mechanisms of DNA repair that in turn, will lead to develop new anticancer therapies.