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
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.
Why do many cancer patients develop delayed metastases? How do metastatic cells survive in a foreign environment? Can we identify disseminated cancer cells before metastatic outgrowth? If you are interested in answering these questions, Montagner lab is looking for two creative, independent, and ambitious Postdocs. Our mission is to identify innovative actionable targets to kill disseminated metastatic cells before the onset of metastasis. In our lab we apply bulk (qPCR, western blotting, cytofluorimetry) and single cell analyses (scRNAseq,immunofluorescence, multispectral imaging, mass cytometry) which encompass a breadth of disciplines (molecular biology, biochemistry, mechanobiology, bioinformatics, optogenetics) spanning diverse areas (cell biology, genomics, and metabolomics, pre-clinical translation, liquid biopsies). The Postdocs will isolate disseminated cells from multiple sources and animal models, generate single cell expression profiles, characterize the microenvironment, develop organotypic systems in vitro and design experiments for orthogonal validation or functional studies (patient-derived cell lines, high content screens, animal models) using technologies available through our group and our collaborators.(Montagner et al., Nature Cell Biology 2020; Zangrossi et al., Cancers 2021; Zangrossi et al., Cancers 2021).
Interested in understanding how blood cells form? A postdoctoral position is available in the laboratory of Dr. Andrea Ditadi at SR-TIGET (Telethon Institute for Gene Therapy at the Ospedale San Raffaele) in Milan to study new layers of regulation of blood development.