Background Gene co-expression networks have been used to define prognostic gene signatures and centrally connected genes as therapeutic targets in cancer. However, most of these studies are purely descriptive, not fully exploiting the wealth of information hidden in the constructed networks to investigate specific biological hypotheses. Moreover, networks have never been compared across breast cancer (BC) subtypes, despite the potential usefulness of such an approach to understand how specific molecular features are established and regulated. Hypothesis We posited that reconstructing BC transcriptional networks could allow us to address biological questions related both to BC in general and to specific BC sub-types. Allowing to formulate testable hypotheses about how biologically/clinically relevant gene expression patterns are established and maintained in specific BC sub-types, such an approach could be exploited to identify and validate potential key regulatory genes, developing them into therapeutic targets. Aims We have implemented a workflow based on the analysis of the METABRIC BC gene expression dataset, which we have validated both based on database analyses and on experimental approaches. We aim at confirming its validity as a tool to dissect molecular pathways linked to BC aggressiveness, particularly basal-like BC for which a targeted treatment is still lacking, identifying key regulatory genes amenable to therapeutic intervention. AIM 1) Discovering how clinically relevant BC gene expression patterns are established by identifying transcriptional regulatory hubs and validating them as therapeutic targets. AIM2 ) Identifying drugs able to target relevant co-expression modules via a drug repositioning approach. AIM 3) Identifying central regulators of specific stromal signatures. AIM 4) demonstrating siRNA-mediated in vivo target ability of identified transcriptional regulators
Applications are OPEN for the PhD program in Molecular Biomedicine of the University of Trieste (Dottorato in Biomedicina Molecolare dell'Università di Trieste)
One Post-Doctoral position is available in the laboratory headed by Carmine Settembre. Work’s topic will be the study of the regulation and medical implication of selective autophagy.
The “Unit of Pathogenesis and Treatment of Immune and Bone Diseases” lab, led by Anna Villa at the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), Milan, Italy is recruiting a highly motivated post-doctoral fellow with strong experience in hematopoietic stem cell biology and bone marrow niche. The project will be focused on the study of ectopic bone marrow niche and optimization of innovative gene correction platform. The research activities of our laboratory are focused on the study of pathological mechanisms of immune and bone diseases and the preclinical evaluation of innovative therapeutic approaches based on gene therapy, gene editing and novel conditioning regimens. As part of the SR-TIGET, a world-leading Institute in the field of gene and cell therapy for the treatment of human genetic diseases, we benefit from a highly competitive, international and scientifically stimulating environment and offer excellent state-of-the-art facilities and infrastructures, and access to clinically relevant human samples.