Ana Carolina Moisés - ESR 11

Name: Ana Moisés

Nationality: Brazilian

Main Host Institution: Netherlands Cancer Institute

Academic Background: I obtained my Bachelor’s degree in Biology at the Federal University of Rio Grande do Sul (Brazil) where I collaborated as a research trainee in Dr. Lavinia Faccini’s group within the Genetics department.

I achieved my Master’s degree in Molecular Biomedicine at the Autonomous University of Madrid (Spain) and completed my final Master dissertation at the Spanish National Cancer Research Centre within the Telomeres and Telomerase group under supervision of Dr. Maria Blasco.

In December 2017 I joined Jos Jonkers’ group (Molecular Pathology department at the Netherlands Cancer Institute) as a PhD student.

Project title: In vivo testing of novel therapeutics alone or in combination with platinum drugs or PARP inhibitors in mouse models of BRCA1/2-deficient breast cancer

Project background: Breast cancer is one of the most commonly diagnosed malignancies in women. Five to ten percent of all breast cancers have a hereditary component, and approximately twenty five percent of all hereditary breast cancer cases can be attributed to germline mutations in the BRCA1 or BRCA2 gene that play a critical role in homology directed repair of DNA double-strand breaks.

Since the available drugs, such as platinum drugs or PARP inhibitors, show limited efficacy due to the emergence of drug resistance, our goal is to find and validate therapies to overcome this problem. The use of in vivo models of breast cancer represents a highly comprehensive and relevant tool for studying the complexity of this human disease.

Project Aim: We aim to test candidate drugs developed by SYNTRAIN beneficiaries that confer synthetic lethality with BRCA1/2-deficiency in vivo, using our established Brca1/2-deficient mouse models. These novel therapeutics will be tested alone or in combination with platinum or PARP inhibitors.

In addition, we will perform in vivo validation of candidate genes that confer resistance or are able to re-sensitize to synthetic lethality drugs that are currently being identified in in vitro genetic screens conducted by Mariana Dias (ESR12), another SYNTRAIN PhD student in our lab.

In parallel, we aim to generate useful tools to test and validate the SYTRAIN therapeutics. Our goal is to introduce concomitant deletion of p53 and specific Brca1 exon domains in vivo to uncover potential tumor suppressor regions of this gene and evaluate the effects of gene disruption on tumor formation, disease progression and therapy response.

Expected Outcome: We expect to validate the results obtained in vitro by the other SYNTRAIN collaborators in vivo and therefore to unveil new therapies for BRCA1/2-deficient breast cancer.