Associate Professor Sergio Gradilone

This lab focuses on understanding the basic biological processes that are involved in the transformation of a normal cell into a malignant one. By understanding these mechanisms, potential therapeutic interventions may be envisioned.

The researchers are currently investigating the role of the primary cilium in tumor biology. Primary cilia are multisensory organelles, like a cell antenna, that sense and receive signals from the environment surrounding the cells. The group has found that these antennae are lost in tumor cells; therefore, they are trying to understand the mechanisms of ciliary loss, and what are the consequences of such a loss. Furthermore, as they gain knowledge on these mechanisms, the researchers are now able to induce the restoration of primary cilia in tumor cells and bring back the malignant cells to a more normal phenotype, which may contribute to the development of new therapeutic strategies based on the rescue of primary cilia integrity.

The group's research is now focused in a specific liver cancer that derives from the epithelial cells of the bile ducts, the cholangiocytes. This cancer, cholangiocarcinoma, is a very aggressive and lethal malignancy, and its incidence has been increasing worldwide during the last decades. Since there is no effective treatment, there is an urgent need of new therapeutic approaches to treat these tumors. Interestingly, the loss of primary cilia has been now also described in other solid tumors like pancreatic, prostate, breast, and kidney cancers, making this group's observations potentially applicable to these malignancies enhancing the significance of their work.

This research is uncovering novel and generalizable information on fundamental, ciliary-dependent mechanisms controlling the proliferation of malignant cells and provide the foundation for plausible, novel anti-cancer therapies based on the restoration of primary cilia architecture and function. By partnering with collaborators directly engaged in the treatment of patients and with pharmaceutical industries, the group's ultimate goal is to translate their basic research to the bedside by developing new clinical trials for these diseases.