The seven-year, $6.4 million grant supports leaders who have made significant contributions in cancer research and are pursuing areas with unusual potential to move the field forward. Chandel, whose work focuses on cellular organelles called mitochondria, will be exploring the mechanisms of mitochondrial metabolism that contribute to tumor formation and investigating related enzymes that may be targeted for future therapies.
“In the last five to ten years, the idea that the metabolism of cancer cells might be different than the metabolism of normal cells has emerged,” he said. “We believe that mitochondrial metabolism is central to tumorigenesis. If that’s true, we have to figure out how that works.”
Mitochondria are known for their ability to produce energy by making a molecule called adenosine triphosphate (ATP). Chandel’s lab has demonstrated that the organelles also have other important responsibilities, such as generating molecules called reactive oxygen species (ROS) that support cell proliferation and adaptation to hypoxia. Thus ROS can activate signaling inside cancer cells that leads to tumor growth, an interaction Chandel plans to study with the support of the new grant.
“We’re going to use CRISPR technology to conduct forward genetic screens in mammalian cells to explain mitochondrial biology in the context of cancer,” he explained.
In previous research, published in the journal eLife, Chandel’s group also showed that metformin, a widely used drug used to treat type II diabetes, can inhibit mitochondrial complex I and reduce human cancer cell growth in mouse models.
“We developed tools that uncovered that this drug can be repurposed as an anticancer agent,” Chandel said. “With the NCI’s award, we’ll continue these studies.”
Chandel is also leader of the Membranes, Organelles and Metabolism Program in the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Three additional Feinberg faculty members received the NCI Outstanding Investigator Award during the program’s inaugural round of funding: Marcus Peter, PhD, professor of Medicine in the Division of Hematology/Oncology, Ali Shilatifard, PhD, chair of Biochemistry and Molecular Genetics, and Maciej Lesniak, MD, chair of Neurological Surgery.