Page 32 - Hormel Report 2021

Sergio Gradilone, Ph.D.
“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
32 | THE HORMEL INSTITUTE // Cancer Cell Biology and
Translational Research
SECTION LEADER / ASSOCIATE PROFESSOR
UNIVERSITY OF MINNESOTA
The “Cancer Cell Biology and Translational Research” section focuses on under- standing the basic biological processes
involved with a normal cell transforming into a cancerous one. By understanding these mech- anisms, potential therapeutic interventions
may be envisioned. We continue investigating the role of the primary cilium in tumor biology. Primary cilia are multi-sensory 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 under- stand the mechanisms of ciliary loss, and what are the consequences of such a loss. Further- more, as we gain knowledge on these mecha- nisms, 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 development 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 thera- pies and translational studies. We briefly describe two of them:
Histone Deacetylase SIRT1 promotes loss of primary cilia in Cholangiocarcinoma. Cholangiocarcinoma (CCA) also known as bile duct cancer, arises from the cholangiocytes, the cells lining the bile ducts in the liver, and is among the deadliest types of human malignancies.
CCA is the second most common primary liver malignancy in adults. CCA is a deadly tumor that develops without pain; therefore, its identification is generally made at a late stage when surgical treatments are excluded, leaving patients with insufficient therapeutic choices. The pathogene- sis of CCA, as well as in other tumors, seems to involve the loss of primary cilia in cholangiocytes (Figure 1). The key findings of this project relate to the regulation of primary cilia expression by