Richard L. Proia, Ph.D.
Genetics of Development and Disease Branch
Building 10, Room 9D06
10 Center Drive
Bethesda, MD 20814
The goal of our work is to understand how an important class of cellular lipids is regulated during normal biology and in disease.
Sphingolipids, the topic of our research, were named after the mysterious Sphinx of Egypt because of their enigmatic properties. It is now well-known that a major function for sphingolipids is to serve as building blocks for cell membranes. Because of their distinctive properties, these molecules form plasma membrane "rafts" and act as binding sites for cells, viruses and toxins.
Sphingolipids also directly function as signaling molecules. Sphingosine-1-phosphate (S1P), a product of sphingolipid degradation, is a regulator of several biological processes. S1P can be produced by all cells and its concentration is high in blood and lymph fluids. It has five high-affinity G-protein-coupled receptors (GPCRs) that are among the most highly and widely expressed of the several hundred member GPCR superfamily. S1P signaling through its GPCRs regulates basic functions in the vascular, nervous, and immune systems.
Sphingolipids are directly involved in human disease. This is most clearly seen in a family of inherited lysosomal storage diseases where blocks in the degradation of sphingolipids cause serious neurodegenerative disorders. Tay-Sachs, Sandhoff and Niemann-Pick diseases are some examples. Now substantial evidence has emerged that implicates sphingolipid metabolism and signaling in more common diseases, such as autoimmune disease, atherosclerosis, cancer, and diabetes.
In our lab, we attempt to discover the functions of sphingolipids in normal biology and in disease using mouse models and cells from patients. We also study how cells express proper amounts of the different types of sphingolipids. Ultimately we can use what we learn from this research to identify new therapies for disease.
Applying our Research
The impact of sphingolipids on biology is important, and its role in human disease is only beginning to be appreciated. A deeper understanding of the system holds potential for the development of novel therapies for human disease.
Need for Further Study
How are the proper levels of sphingolipid maintained in cells?
- Ph.D., University of Texas Southwestern Medical Center, 1980
- B.S., Bates College, 1976
Blaho VA, Galvani S, Engelbrecht E, Liu C, Swendeman SL, Kono M, Proia RL, Steinman L, Han MH, Hla T. HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature. 2015;523(7560):342-6.
Galvani S, Sanson M, Blaho VA, Swendeman SL, Obinata H, Conger H, Dahlbäck B, Kono M, Proia RL, Smith JD, Hla T. HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci Signal. 2015;8(389):ra79.
Proia RL, Hla T. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest. 2015;125(4):1379-87.
Allende ML, Proia RL. Simplifying complexity: genetically resculpting glycosphingolipid synthesis pathways in mice to reveal function. Glycoconj J. 2014;31(9):613-22.
Kono M, Tucker AE, Tran J, Bergner JB, Turner EM, Proia RL. Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo. J Clin Invest. 2014;124(5):2076-86.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on March 20th, 2018