The major accomplishment of our laboratory is advancing the idea that sphingolipids (e.g. ceramides) contribute to insulin resistance and metabolic disease. This prior work involving cell culture and rodent model systems has revealed considerable new mechanistic insight into the role of these molecules as central regulators of nutrient homeostasis. This focus on basic science and discovery biology will continue to be a major component of our laboratory. However, we now endeavor to also translate these findings into new clinical procedures or behavioral interventions to improve health.
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 new 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.
The next phase of our laboratory also involves increased translation of our discoveries into testing therapies into humans or using diagnostic measures to identify subjects that are at risk. For example, we have identified mutations in ceramide-synthesizing genes that may influence an individual’s risk of diabetes and various cardiovascular complications. Moreover, in conjunction with the Center for Clinical and Translational Studies we are testing new therapeutics that may have applicability in human subjects.
We remain optimistic that our work on this pathway will uncover new fundamental sensing mechanisms that have clinical applicability. We welcome you to explore our website and contact us should you wish to join our team.