2018 Grantee: Iok In Christine Chio, PhD
Columbia University Medical Center
Research Project: Targeting Redox Status and mRNA Translation in Pancreatic Cancer
Award: 2018 The Ruth and Frank Pratte Foundation Pancreatic Cancer Action Network Catalyst Grant
Award Period: July 1, 2018 – June 30, 2021
Dr. Chio trained in the field of immunology, inflammation and cancer at the University of Toronto in the laboratory of Professor Tak Wah Mak, a leading scientist in the field. As a postdoctoral fellow in Dr. David Tuveson’s laboratory at Cold Spring Harbor Laboratory, she focused on how pancreatic cancer begins and develops (pathogenesis). She contributed to the development of the first “organoid” system of pancreatic cancer, a way to three-dimensionally model a tumor within the pancreas and its surrounding tissue. Dr. Chio’s findings have opened an exciting new area in the understanding of pancreatic cancer pathogenesis and have important implications for the treatment of these tumors.
Among the reasons that pancreatic cancer has a poor prognosis are the lack of effective treatments and the cancer cells’ development of drug resistance. Almost all pancreatic cancer cases are driven by mutations in a protein called KRAS, but there is not currently a treatment strategy to directly block the activity of KRAS.
During her postdoctoral studies, Dr. Chio focused on a protein called NRF2, which is a transcription factor. Transcription factors influence the cells’ ability to translate genetic information in DNA and RNA into activated proteins that bring about the cells’ cancer-like abilities. She and her colleagues discovered that pancreatic cancer cells, in the presence of mutant KRAS, depend on the activity of NRF2. However, like KRAS, NRF2’s activity cannot currently be blocked by a treatment strategy.
Dr. Chio found that NRF2 is involved in controlling a process called oxidation, through which cells react to low oxygen conditions that are typical of the pancreatic cancer cells’ environment. She therefore proposes to utilize organoids, or three-dimensional laboratory models of pancreatic cancer and its surrounding tissue, to better understand how NRF2 controls protein expression through regulating the process of oxidation. The research team will also explore whether oxidative regulation of protein synthesis could be leveraged to stop or slow the tumor’s growth.
These results will serve as the basis for future clinical investigations of new drugs to target the protein synthesis processes in pancreatic cancer patients.