Research

Youssef Zeidan, MD PhD

My research focuses on the role of sphingolipids in ionizing radiation stress responses. Over the past two decades sphingolipids have evolved as key bioactive lipids in cellular stress responses. Radiation injury induces changes within tumor cells and tumor microenvironment through the sphingolipid second messenger, ceramide. Ceramide can be generated through the de novo or sphingomyelin hydrolysis pathways. Our work in breast cancer cells identified a novel mechanism for regulation of acid sphingomyelinase, a key enzyme in radiation response. One of our major interests is to understand how aberrations in ceramide metabolism contribute to radiation resistance. In particular, various sphingolipid species will be analyzed by mass spectrometry and correlations will be made to enzymatic activities. Both cell culture and mouse models are used. Another focus of the laboratory is to study the contribution of sphingolipid metabolism to radiation–induced normal tissue injury. This is often a challenge that hinders the ability to deliver escalated and potentially curative radiation doses. Finally, a library of ceramide analogues will be tested as potential radiosensitizers or radioprotectants.