Cancer Cell Biology & Translational Research
Sergio Gradilone, Ph.D.
Assistant Professor

The Hormel Institute - Sergio Gradilone Lab

(Left to right) Kristen Thelen, Sergio Gradilone, Adrian Mansini, Maetzin Cruz-Reyes

Our section started in November 2014 and we equipped the new laboratory, putting together a small team to start moving our research forward. The “Cancer Cell Biology and Translational Research” section focuses on understanding the basic biological processes involved with a normal cell transforming into a cancerous one. By understanding these mechanisms, potential therapeutic interventions might be envisioned. We currently are investigating the role of the primary cilium in tumor biology. Primary cilia are multisensory organelles . similar to a cell 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 now are able to induce the restoration of primary cilia in tumor cells and bring back the malignant cells to a more normal phenotype, which might contribute to the development of new therapeutic strategies based on the rescue of primary cilia integrity. The lab primary cilia research is focused now on an aggressive, lethal form of liver cancer known as .cholangiocarcinoma. that derives from epithelial cells of the bile ducts. Its incidence has been increasing worldwide in recent decades and there is no effective treatment for it. Loss of primary cilia also has been described in other solid tumors . including pancreatic, prostate, breast and kidney cancers . broadening the spectrum of potential applications of this research. During our time at The Hormel Institute, our section brought a federal grant form NIH/NCI (R21 CA166635) and secured new funding for the coming five years (R01 CA183764), also from the National Cancer Institute, part of the National Institutes of Health. We established several collaborations, both intraand extramural, with prestigious investigators and institutions including: Dr. Mohammad Saleem Bhat (The Hormel Institute); Drs. Nicholas LaRusso and Steven Alberts (Mayo Clinic Rochester, MN); Drs. Kabir Mody and Debabrata Mukhopadhyay (Mayo Clinic, Jacksonville, FL); Dr. Aram Hezel (University of Rochester School of Medicine, Rochester, NY); Dr. Mina Komuta (Cliniques Universitaires Saint-Lu, Brussels, Belgium); Dr. Jesus Banales (Biodonostia Research Institute -Donostia University Hospital, San Sebastian, Spain); and Acetylon Pharmaceuticals Inc. (Boston, MA), among others. The results of our research are 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, our ultimate goal is to translate our basic research to the bedside by developing new clinical trials for these diseases.

“Loss of primary cilia also has been described in other solid tumors –
including pancreatic, prostate, breast and kidney cancers – broadening
the spectrum of potential applications of this research.”
Dr. Sergio Gradlione

Sergio Gradilone Lab Shot - The Hormel Institute

 

The Hormel Institute - Sergio Gradilone Lab Cells

Primary cilia are loss in tumor cells. This confocal immunofluorescence
shows the albescence of primary cilia in human cholangiocarcinoma
samples (CCA) compared to normal liver samples.