An Indiana University scientist has received a five-year, $2.2 million award from the National Institutes of Health to continue research that uses fruit flies to understand why cancer cells consume large amounts of sugar.
Jason Tennessen, an associate professor in the IU Bloomington College of Arts and Sciences' Department of Biology, has been given a five-year extension on the NIH's Maximizing Investigators' Research Award, or MIRA, he received in 2016. The grant is part of the National Institute of General Medical Sciences' Outstanding Investigator Award Program, which encourages more ambitious, longer-term research projects with higher probability of breakthrough discoveries.
Tennessen's research is focused on understanding why tumors and certain other types of growing cells and tissues become increasingly reliant on a unique type of sugar metabolism, known as aerobic glycolysis or the Warburg effect, for both energy production and biosynthesis. The unique manner by which tumors use aerobic glycolysis suggests that understanding how this metabolic program is regulated is essential in developing new cancer therapies.
Tennessen discovered that the fruit fly Drosophila melanogaster also uses aerobic glycolysis to support rapid growth. This discovery is important because it provides a powerful genetic model for precisely studying the molecular mechanisms both activate and shut off the Warburg effect within living animals—an endeavor that has proven difficult in mammals.
The importance of using flies to study aerobic glycolysis is already apparent from the initial work funded by Tennessen's MIRA. During the first five years of this award, the Tennessen lab discovered that activation of aerobic glycolysis within growing fruit flies results in the production of a compound known as L-2-hydroxyglutarate. In humans, this compound promotes the growth of kidney tumors and leads to birth defects.
"This discovery was significant," notes Tennessen. "Our studies establish the fly as the premier genetic model system for understanding how normal cells can produce a compound that promotes tumor formation in human."
Ongoing research in the Tennessen lab was also the first to show how the molecule functions in a living system where cancer is not present. By understanding how the molecule works in healthy cells will help researchers determine how it causes human disease.
During the next five years of his MIRA, Tennessen will continue to use the fly as a model to investigate aspects of tumor metabolism that are difficult to study in other systems. In addition to the studies described above, Tennessen's lab will determine how fruit flies terminate aerobic glycolysis at the end of their juvenile growth period.
"The predictable manner by which flies turn off aerobic glycolysis when they stop growing is the opposite of tumors, where uncontrolled growth results in continuous activation of this metabolic program," explains Tennessen. "We hope that by understanding how aerobic glycolysis is shut down in flies we can identify novel means of shutting down the same metabolic program in cancer cells."
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