Cancer Center Team Receives $11M NIH Grant to Research the Role of Sphingolipids in Cancer

An interdisciplinary research team led by Yusuf Hannun, MD, the Joel Strum Kenny Professor in Cancer Research in the Renaissance School of Medicine (RSOM) at Stony Brook University, has received an $11 million five-year grant from the National Institutes of Health (NIH) to investigate the role of sphingolipids (SLs), a class of fat molecules that regulate many of the key cell pathways and functions in cancers.

The grant, awarded by the NIH National Cancer Institute, runs to the end of August 2030. It is the only NIH Program Project Grant, also called a P01, awarded this year to a State University of New York school. These NIH P01 grants support long-term research programs that have a specific major objective or a basic theme.

The SL class of lipids regulates many important functions that are critically related to cancer processes such as differentiation, cell death, metastasis and response to cellular stresses. Additionally, some SLs also play a key role in the action of chemotherapeutic agents used to treat cancer.

“This award represents a major milestone for our institution and an important advancement in cancer research,” said Raymond Bergan, MD, director of the Stony Brook Cancer Center. “The NIH grant is yet another measure of the stature of our Cancer Center and its national leadership in understanding the role of lipids and metabolism in the formation of cancer and how that knowledge can be applied to prevention and treatment.”

Hannun, principal investigator of the NIH grant, explains that one unique aspect of investigating SLs in cancer is that their roles are important in so many aspects of cancer treatment, including chemotherapy, immunotherapy, radiation therapy and metabolic approaches.

“While our research with the help of this grant will be broad and far-reaching, we will initially focus on SLs in breast cancer development and therapy, the action of DNA damaging chemotherapies, and mitigating toxicity of chemotherapy,” he said.

To date the team has focused on SLs in breast cancer and to a lesser degree liver cancer. They will continue to target SL research around these forms of cancer but also in lung cancer and leukemias.

An Experienced Investigative Team

The investigative team that Hannun has assembled for the SLs research program has collectively worked for decades in this area of cancer research, having jointly published more than 250 peer-reviewed manuscripts. The group brings expertise from multiple disciplines, including biochemistry, medicine, pathology, physiology and pharmacology.

Over the years, they have made seminal contributions to the field. These include identifying several enzymes of SL metabolism as important targets for developing novel cancer therapeutics; developing lead compounds for anti-cancer therapeutics; discovering important functions of specific SL enzymes in regulation of cancer biologies such as migration, survival, inflammatory and immune responses; and roles in cancer therapeutics, including SLs as biomarkers.

Leading team members include:

• Daniel Canals, research assistant professor in the Department of Medicine, whose work focuses on the molecular mechanism of SLs in migration and adhesion of cancer cells critical to regulating cancer progression and metastasis, and an expert in advanced analysis of SLs
• Christopher Clarke, associate professor of research in the Cancer Center, who studies oncogene signaling and how this reprograms SL metabolism to promote cancer development and progression
• Chiara Luberto, associate professor in the Department of Physiology and Biophysics, whose lab currently investigates regulation of SLs in breast cancer and rare leukemias to leverage SL metabolism in enhancing response to chemotherapy
• Cungui Mao, professor of medicine in the Division of Gastroenterology and Hepatology, whose work has centered on metabolism and signaling functions of SLs in different species from yeast to mammals with a current focus on how to mitigate some of the most debilitating and dose-limiting actions of key chemotherapy agents
• Fabiola Velazquez, an expert in pre-clinical models who researches a particularly active type of SL as a potential novel anticancer intervention

Together, they will collaborate with other scientists at Stony Brook and around the country to advance SLs research findings from basic and translational work to new treatments.

This group, formally called The Lipid Cancer Laboratory, is a major part of a larger group of investigators who research lipids in cancer under the Lipid Signaling and Metabolism in Cancer Program. It is one of three major broad research programs dedicated to cancer discovery and therapeutics in the Stony Brook Cancer Center.

Currently, the only approved SL-based therapeutics in medicine are for inflammatory bowel disease and multiple sclerosis. There are also some ongoing pre-clinical and clinical studies with SLs-based compounds as treatment options for cancer.