Julie Saba studies the functions and metabolism of sphingosine 1-phosphate (S1P), a ubiquitous bioactive sphingolipid involved in the regulation of an array of physiological and pathological processes. S1P signaling is required for angiogenesis and immune cell trafficking, and a role for S1P has been implicated in carcinogenesis, allergy, inflammation, platelet aggregation, thrombosis and ischemic preconditioning. S1P generally promotes cell survival and prevents apoptosis through intracellular and extracellular mechanisms. Dr. Saba’s early work led to the isolation of a yeast gene encoding sphingosine phosphate lyase (SPL), the enzyme responsible for the major route of catabolism of S1P. Isolation of the first SPL gene sequence in yeast led to the subsequent identification of other genes of S1P metabolism and has facilitated isolation and characterization of SPL enzymes from various species, including Drosophila, C. elegans, Mus musculus and Homo sapiens. Dr. Saba’s laboratory has been investigating the role of SPL in biology, development and disease by studying its expression and activity in normal versus diseased tissues and by analyzing the biochemical and phenotypic consequences of manipulating SPL expression in genetically tractable organisms and in mammalian cells. Her studies have established that SPL expression is essential for normal development and tissue integrity, that somatic SPL mutations are responsible for human disease, and that SPL expression is downregulated in some cancers. Current studies are focused on further characterizing the role of SPL in cancer and modulating SPL activity to treat human illnesses.