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Targeting metabolic vulnerabilities of melanoma metastasis in lymph

Jessalyn Ubellacker, PhD

Mentor Brendan Manning, PhD
Award Type Career Development Award
Institution Harvard University

The major reason melanoma causes illness and death in patients is because the melanoma cells from the skin can travel to lymph nodes or into the blood which allows them to spread and grow in other organs in the body, such as the lung or liver. We do not yet fully know how melanoma cells are able to travel into the lymph or blood. However, the harsh environment of the blood kills most of the melanoma cells before they make it to other organs. Only melanoma cells that have specific changes to small molecules inside the cell that help protect the melanoma cells against stress survive in the blood and then grow at organs distant from where the initial melanoma was located on the skin.

My previous work discovered that melanoma cells that travel to the lymph acquire changes to lipids inside of the cell that then shield them from stress in the blood. Specifically, I found that melanoma cells that acquired a fatty acid called oleic acid from the lymph were protected from stress and by blocking this oleic acid the cells were not able to travel to distant organs as efficiently. In addition to these recent changes, I anticipate that melanoma cells undergo many more changes to the fatty acids and other lipids inside of the cell that will shield them from the stress the cells experience when they travel through the bloodstream. I believe these changes remain to be discovered.

The goal of my proposal is to investigate these additional lipid changes in the melanoma cells that are allow them to survive better in the blood. Then, my lab group will work to block those changes from occurring to prevent the cells from traveling to and growing in other organs in the body, such as the lung or liver. This project has the potential to help block early-stage melanoma from spreading to distant organs and causing illness and death in patients. If we can identify the lipid changes that help protect melanoma cells and discover ways to prevent those changes from occurring we will be able to develop new treatments to help patients diagnosed with early-stage melanoma.