Physical biology of cancer and computational oncology

Cell-cell and cell-microenvironment interactions are important factors in the process of tumorigenesis and cancer progression. Emerging evidence points at the pivotal role of physical interactions in regulating growth and proliferation. In particular, the correct balance of adhesive forces and cytoskeletal tension guided by chemical polarity cues allows the formation and maintenance of normal tissues, and can be severely disrupted in cancer. Physical, mechanical, and biochemical cues contribute to determine the formation of polarized compartments, the orientation of the cell division axis, the direction of cell migration. Such single-cell level signals are integrated to give highly non-trivial multicellular dynamics, such as collective migration and invasion. 

Control of gene expression, mainly mediated by transcription factors and microRNAs, is crucial for the normal development and maintenance of healthy cells, and alterations from standard coordination programs can lead to severe diseases, including cancer. The actions of transcription factors and microRNAs are often highly coordinated.

We aim at characterizing the physical factors that control the development and maintenance of normal tissue architecture, and the role of their alterations in cancer. In particular, we apply a complex of experimental, modelling, and computational approaches to the study of the following processes:

i) in vitro growth of epithelial 3D-structures using breast and kidney cell lines; 

ii) in vitro aggregation of prostatic cancer cells; 

iii) in vitro and ex vivo tumor-stroma interaction, by co-culturing prostate, breast and colon cancer cells with cells derived from mouse aortic rings.

We are moreover developing a systems biology analysis of the interplay among transcriptional and post-transcriptional layers in regulatory networks, taking into consideration the emerging role of lncRNAs. We will also consider the application of deep-sequencing technologies to the investigation of these regulatory networks.