Of the 4000 sphingolipids that accrue in tissues, which ones are biologically active and which are relevant to metabolic disease?

Through what mechanisms do cells translate small changes in sphingolipid levels into profound effects on nutrient homeostasis?

Where do sphingolipids act (i.e. which tissues and which organelles)?

When in the timeline of events leading to metabolic disease do sphingolipids accumulate? What regulatory mechanisms govern rates of ceramide synthesis or degradation?

Why did sphingolipids evolve such prominent roles in nutrient homeostasis?

How do we exploit this knowledge to improve human health?

Using cultured cells, rodent models, and clinical profiling we seek to address these questions. For example, owing to new genetic engineering approaches (e.g. CRISPR), we have generated a dizzying array of new mouse models allowing for the selective modulation of sphingolipids in specific tissues. We benefit greatly from the resources at the University of Utah, which has outstanding cores such as its Metabolic Phenotyping and Metabolomics facilities to help advance these research goals.