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The lipid: humble origins to cancer and aging treatments

Dr. Lina Obeid, dean for research and professor of medicine at Stony Brook University. Photo courtesy of Stony Brook University

The same lipids that make up the membranes of our cells are now being found to play a role in the development of cancer and aging.

For years, these fat molecules—including those called ceramide—were thought to only be important for structural reasons. The role of these lipids was only to provide a boundary for each cell and control what enters and exits the cell.

Recent research has documented the role of these lipids in cell signaling, revolutionizing the way scientists examine the mechanisms behind aging and cancer.

The extent of this change can be seen in a search of scholarly articles. From 1960 to 1985, only three articles were published regarding the lipid ceramide and its role in signaling. In the next 25 years, this number increased by more than 900 times as 2,825 articles have been published regarding the topic from 1986 to 2011. This incredible growth was reflected in the sentiments of Dr. Lina Obeid, dean for research and professor of medicine at Stony Brook University.

“The interest in genomics eventually turned into an interest in proteomics because genes code for proteins,” Obeid said. “Now, the interest is turning to the lipidome because lipids are the products of the proteins. Lipids are the next step, the unstudied future, and the new frontier.”

Obeid is dedicated to exploring this new frontier and her research is the first to document the role of ceramide in cancer and aging. Ceramide and its products play an important role in cancer and aging, and the function of the lipid is dependent on key enzymes that Obeid has discovered. These enzymes work like fixed-size wrenches that can only screw and unscrew bolts of a specific size.

Beginning with ceramide, Obeid explained, the enzyme cDase unscrews the structure, creating an intermediate product. Then, another enzyme, SK, screws the molecules into a new structure making sphingosine 1-phosphate, another lipid,  Obeid said. Therefore, as  Obeid noted, the enzymes are key to regulating the amount of ceramide and sphingosine that is present. Each product causes drastically different results. Ceramide plays a role in cell death, which is beneficial when cells are cancerous or made incorrectly, but it also plays a role in aging, according to Obeid.

Contrastingly, Obeid also noted that sphingosine plays a role in cell growth, which can lead to inflammation or proliferation of cancer cells. The goal, as  Obeid enunciated, is to regulate the enzymes and in turn regulate aging and cancer.  Obeid’s preliminary studies have shown great promise in achieving this. She has shown that when the enzyme SK is knocked out and sphingosine cannot be made, cancer does not occur.

However, this means that the compound is present in higher quantities as ceramide, and can potentially accelerate aging. On the other hand, if ceramide production is regulated, aging can be reversed, but there are greater chances for cancer. While explaining this, Obeid joked about this catch-22, saying that “it seems that there are only two choices, aging or cancer.”

All joking aside, Obeid is dedicated to translating these findings into clinical use. She plans to focus on specific drug development to inhibit pathways and target or deregulate enzymes of sphingosine production in an effort to treat cancer. These drugs can be optimized depending on the specific symptoms and needs of individual patients.

The humble lipid has transformed into a key player in the battle of cancer and aging. Understanding and regulating its role is sure to revolutionize treatment options in the near future.

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