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Understanding how the Hippo pathway controls immune response to cancer

To grow, cancers overcome a series of biological mechanisms that control our normal cell functions. The “Hippo” pathway is one of these mechanisms. When it’s working correctly, it ensures that cells multiply normally and tissue grows without a problem. But when something goes wrong with it, problems develop: cells reproduce uncontrollably, tissue balloons in size, and tumours are formed.

Years of research have allowed scientists to better understand how this pathway works. But even today, little is known about the ways in which alterations in this pathway affect our immune system’s ability to detect and fight cancer cells. With new funding from the Terry Fox Research Institute, Dr. Hartland Jackson, an investigator at the Lunenfeld-Tanenbaum Research Institute (LTRI) at Sinai Health, will try to shed new light on this relationship.

“The aim of this project is to really understand how the Hippo pathway influences the ability of the immune system to fight or help tumour growth,” says Dr. Jackson, one of four 2022 Terry Fox New Investigator awardees. “Ultimately, our hope is that the insights gained through this work will extend our understanding of the Hippo pathway and provide opportunities to harness the power of the immune system to fight cancer.”

Over the next three years, Dr. Jackson will receive $450,000 to perform this research. With this support, he and his team will be able to use cutting-edge imaging technologies and advanced models to better map the areas immediately surrounding a tumour, seeing how Hippo alterations recruit or reject immune cells, and deciphering the exact mechanisms through which this occurs.

The team will also receive mentorship from a world-leading group of researchers studying the Hippo pathway, a Terry Fox New Frontiers Program Project Grant team based at LTRI and led by Dr. Jeffrey Wrana. This collaboration will enable Dr. Jackson and his team to access some of the best brains in the area and to see the impact that potential drugs that target Hippo pathway alterations have on the immune system.  

“To create new therapies that target the Hippo pathway, we need to know how both the tumour and the immune system react to a drug to determine if it will be beneficial or detrimental to a patient,” says Dr. Jackson.

“Dr. Jackson is an outstanding new investigator who we were incredibly fortunate to recruit to our team,” says Dr. Jeffrey Wrana. “His strategy to explore the molecular dynamics of cancer with the spatial resolution of individual cells, promises to illuminate the architecture of a tumour and its interaction with the immune system in exquisite detail. This will undoubtedly reveal new ways to re-awaken the immune system to attack tumours.”

Mentoring Program: Targeting the Hippo Signaling Network In Cancer