Page 30 - Hormel Institute Annual Report 2021-22

Sergio Gradilone, PhD
“Our research is uncovering novel and generalizable information on fundamental, ciliary-dependent mechanisms controlling the proliferation and migration of tumor cells, and provide the foundation for anti- cancer therapies based on the rescue of
primary cilia functions, i.e Ciliotherapy.”
Sergio Gradilone
30 | THE HORMEL INSTITUTE // Cancer Cell Biology and
Translational Research
ASSOCIATE PROFESSOR
UNIVERSITY OF MINNESOTA
Our lab focuses on understanding the basic biological processes involved with a normal cell transforming into a cancer-
ous one. By understanding these mechanisms, potential therapeutic interventions may be envisioned. We continue investigating the role of the primary cilium in tumor biology.
Primary cilia are multisensory organelles – similar to an antenna – that sense and receive signals from the environment surrounding
the cells. We’ve found that these antennae are lost in tumor cells; therefore, we are trying to understand the mechanisms of ciliary loss,
and what the consequences are of such a loss. Furthermore, as we gain knowledge on these mechanisms, we 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 develop- ment of new therapeutic strategies based on the rescue of primary cilia integrity.
Current research projects
Our laboratory has several projects under three categories: 1 - Mechanisms of Ciliary Lost,
2 - Consequences of Ciliary Lost, and 3 - New therapies and translational studies. We briefly describe two of them:
Short Chain Fatty Acid, butyrate, induces cilia formation and potentiates the effects of HDAC6 inhibitors in Cholangiocarcinoma cells. Cholangiocarcinoma (CCA) or bile duct cancer, is a deadly form of liver cancer with limited therapeutic approaches. The pathogenesis
of CCA involves the loss of primary cilia in cholangiocytes by a mechanism involving increased expression of deacetylases like HDAC6 and SIRT1. Therefore, cilia restoration may represent an alternative and novel thera- peutic approach against CCA. The short-chain fatty acid butyrate is a bacterial byproduct from the fermentation of dietary fibers in the intestine and has been shown to inhibit SIRT1,