Dr. Lisa PorterBiological Sciences, University of Windsor
Role of Spy1 in Hepatocellular (Liver) Carcinoma
Co-Investigators and Collaborators:
- Dr. Sindu Kanjeekal, Windsor Cancer Program, Windsor Regional Hospital
- Dr. Akmal Ghafoor, Windsor Cancer Program, Windsor Regional Hospital
- Dr. John Mathews , Windsor Cancer Program, Windsor Regional Hospital
- Dr. Tarek Elfiki , Windsor Cancer Program, Windsor Regional Hospital
- Dr. Abdulkadir Hussein, Mathematics & Statistics, University of Windsor
- Dr. Kevin Milne, Kinesiology, University of Windsor
- Dr. Cheri McGowen, Kinesiology, University of Windsor
- Dr. Matt Krause, Kinesiology, University of Windsor
EVIDENCE OF PROGRESS
Liver cancer is an aggressive disease that is becoming increasingly prevalent. The most common form of cancer that begins in the liver is hepatocellular carcinoma (HCC), and each year approximately half a million people world-wide are diagnosed with this disease. Stressors including diet, inherited disorders, alcoholism and viruses can cause fat deposits to form in and around the cells of the liver, putting an individual at risk of developing HCC. These fat droplets trigger an inflammatory reaction that leads to death of cells in the liver and subsequent growth of healthy cells to compensate for this loss. The precise mechanism tipping this balance to favour the start of liver cancer to start is not known. With Seeds4Hope funding the Porter Lab at the University of Windsor has discovered a protein, called Spy1, that causes a pronounced fat accumulation in the liver and drives the initiation of HCC. They have proven in human cells that this protein causes an increase in fat production in liver cells and accelerated growth. In a mouse model that has shown that the Spy1 protein overrides protective fibrotic liver changes to favour cellular overgrowth. This exciting data may reveal an early detection marker for HCC and a potential therapeutic target for aggressive liver cancer.
In the next year of funding the Porter lab is determining the mechanism by which this protein increases fat production in the liver and using a new mouse model to definitively prove that fibrotic changes associated with a cirrhotic liver are in fact not directly related to the initiation of HCC but rather a protective response to continued damage. We are also starting to work with our kinesiology partners to determine whether diet or exercise can circumvent the changes seen with Spy1.
MEASURES OF PROGRESS
A) Manuscripts and Publications: One manuscript (B. Fifield, C. Stovanovich and L.A. Porter) is in preparation for submission.
B) Conference Presentations: Three conference presentations have been given based on this work: two in Windsor, Canada, and one in Toronto, Canada [NOTE: One of the presentations received the 2016 Franklin & Holder Award for top presentation.]
C) Grants Submitted: CCSRI Innovation Grant (2017-2019) – Role of Spy1 in Hepatocellular Carcinoma; Clinical Utility as a Novel Target. ($300,000) **This grant will address the next steps in this project to move into patient samples and more clinical application. If funded it will be a perfect complement to accelerate the basic science information we are gathering from the mouse model! If not funded we can use the reviewers comments, and year 2 progress to increase our chances of funding immediately after the S4H funding has concluded.