Centro Nacional de Biotecnología CSIC (CNB)
DESCRIPTION OF THE OFFER
The Yes Associated Protein or “YAP” is heavily implicated in cancer progression. YAP is a cytoplasmic protein which, when phosphorylated, acts as a transcriptional co-activator of several genes involved in promoting cell proliferation and in shutting down apoptosis. Specifically, YAP is a cofactor of the TEAD family of transcription factors. Certain small molecule drugs can bind to YAP and interfere with the YAP-TEAD interaction, thus frustrating the transcriptional role of YAP.
The aim of the Peptide-Guided Theranostics lab is to develop clinically translational targeted therapies. To inhibit YAP, we recently developed a series of peptide-drug conjugates, where the drug is a YAP inhibitor, and the peptides are targeting peptides that home to solid tumors by binding to receptors overexpressed on Tumor Associated Macrophages (TAMs) or Cancer Associated Fibroblasts (CAFs). In vivo, we have already shown that some of these conjugates limit tumor growth and extend survival, in a mouse model of breast cancer.
The aim of this final master’s project is to study, in vitro, the effect of peptide-targeted YAP inhibition on the cell viability and phenotype of cultured TAMs and CAFs, using our developed peptide-drug conjugates; with the longer-term vision of applying them, alone or in combination, to treat different solid tumors.
Biomolecules & Cell D.