Research activity

1. Modulation of ErbB receptors signaling to drive cancer cell fate. ErbB is a family of membrane receptors, classically thought to promote cell survival and cell growth and whose activity often is exacerbated in solid tumors. A member of this family, ErbB2, is over-expressed in 20% of breast cancers, and ErbB2 positive tumors are generally more aggressive than Erbb2 negative ones. Several antitumoral drugs target ErbB2 to arrest tumor cell growth, but tumor cells can adapt to resist to these therapies. In our lab we have identified a novel mechanism to modulate the ErbB2 signaling, that could be in principle used to oppose cancer cell resistance to ErbB2-targetted therapies.
2. Characterization of transcription factors with oncogenic or tumor-suppression potential at the single molecule level. We have pioneered a single- molecule approach to quantify the interaction kinetics between nuclear proteins (transcription factors) and their binding sites on DNA in living cells, and we are currently applying it to dissect the causes that underlie activation and inactivation of those transcription factors that act as tumor suppressors or oncogenes in cancer settings. We first characterized the single molecule behavior of the tumor-suppressor p53 (a fundamental transcription factor fundamental for maintaining genomic integrity and frequently mutated/inactivated in cancer). We are now applying our technique to test therapeutic strategies that could be used to reactivate p53 in breast cancer and in neuroblastoma.
3. Dissecting the translation reprogramming mechanisms as a targetable vulnerability in breast cancer. Multiple microenvironmental cues, such as nutrients and oxygen deprivation and inflammatory cytokines, have been implicated in driving cancer metastatic potential, metabolic rewiring and drug resistance. We recently found an evolutionarily conserved mechanism by which the cancer cell responds to microenvironmental stimuli activating a stress response signalling cascade converging on peIF2a-ATF4 axis. This adaptive response provides the cell with a selective advantage in terms of survival and proliferation. Metabolic stress above threshold leads to maladaptive response resulting in activation of apoptotic pathways. The fine-tuning of peIF2a-ATF4 stimulation could tip the cell fate from proliferative to apoptotic. Since cancer cells exploit this conserved mechanism to survive, bypass senescence, and metastasize, we want to exploit this vulnerability to harness breast cancer.