Researcher at Bellvitge Biomedical Research Institute (IDIBELL), Gynecologic Cancer Group, Oncobell Program.
University of Barcelona
Loss-of-function screenings based in the interference of RNA have been successfully used in the last decade to identify new therapeutic targets. The use of shRNA pooled libraries allowed to individually investigate the phenotype associated to the individual silencing of genes at a genome wide scale. The integration of whole genome shRNA screenings with sequencing data led to a new classification of breast cancer based in their vulnerabilities. Recently, the availability and simplicity of the design of strong gRNAs, has enhanced the use of CRISPR libraries in the search for cancer cell weaknesses. Genome-scale CRISPR-Cas screens have already identified essential genes in various cell lines, uncovered genes related to response to small-molecule inhibitors and to sensitivity to cellular toxins.
Using a shRNA library against the entire human genome we described that the JAK/STAT3 pathway is activated and essential for HER2 + breast tumors. Activation of this pathway further leads to an increase in the expression of S100A8 and S100A9 that promote the proliferation of tumor cells. The use of specific inhibitors of the JAK/STAT3/S100A9 pathway reduces the growth of tumors and represents an alternative for the treatment of patients with HER2+ tumors that do not respond to current treatments.
We have recently set up the conditions to generate custom CRISPR libraries and created the first CRISPR KO library against all the protein glycosylation-related genes. Thanks to this newly generated tool we aim to find new and more efficient targets for the treatment of breast cancer.
Ruth Rodriguez studied Biochemistry in the Autonomous University of Barcelona and obtained her PhD in Biology in the Cancer Research Center in Salamanca. In 2010, she joined Dr. Silva laboratory at the Columbia University, NY, USA, and later in the Mount Sinai School of Medicine, NY, USA, where she started using pooled genetic screens to find new targets for the treatment of breast cancer. After six years of postdoctoral experience, she moved to Newcastle University, UK, where she was awarded a Marie Sklodowska-Curie Fellowship to standardize the conditions to generate custom CRISPR libraries. In April 2018, she joined the University of Barcelona as a Ramon y Cajal Researcher to continue her research in cancer.
Group Leader of the Colorectal Cancer Group, Oncobell Program, IDIBELL