Page 28 - Hormel Report 2023

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
28 | THE HORMEL INSTITUTE // Cancer Cell Biology and
Translational Research
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 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 are the consequences 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:
Cholangiocyte Ciliary Defects Induce Sustained Epidermal Growth Factor Receptor Signaling.
A broad group of diseases have defects in their cellular antennae, i.e. the primary cilium. Polycys- tic liver diseases, which are rare genetic disor- ders, are primarily caused by mutations in PKD1, PKD2, PKHD1, and other genes whose products are linked to malfunctions of the primary cilia, leading to chronic liver dysfunction. Furthermore, as mentioned before, bile duct cancer cells are also associated with defective ciliary expression. The epidermal growth factor receptor (EGFR) signaling pathway regulates growth and prolif- eration in almost all human cells, and aberrant EGFR signaling induces disease progression