Richard Leonard Proia, Ph.D.

Senior Investigator

Genetics and Biochemistry Branch

NIDDK

Building 10, Room 9D06
10 Center Dr
Bethesda, MD 20814

+1 301 435 6504

richard.proia@nih.gov

Research Topics

To devise therapies for the diseases of sphingolipid metabolism.

Current Research

Sphingolipids, the topic of our research, were named after the mysterious Sphinx of Greek mythology because of their mysterious 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 structural characteristics, these molecules form plasma membrane "rafts" and act as binding sites for cells, viruses and toxins.

Sphingolipids also function directly 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 relatively high in blood. It has five high-affinity G-protein-coupled receptors (GPCRs) that are highly and widely expressed. 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 disorders where blocks in the degradation of sphingolipids cause rare but, in many cases, fatal disease. These lysosomal storage disorders include Tay-Sachs disease, Sandhoff disease, Gaucher disease, Fabry disease, Krabbe disease, Farber disease and GM1 gangliosidosis. Disturbances in sphingolipid metabolism and signaling have also been linked to cancer and diabetes.

In our lab, we aim to discover the functions of sphingolipids in normal biology and in disease using genetic approaches in mice and in patient cells. Ultimately we aim to devise therapies for the diseases of sphingolipid metabolism.

Applying our Research

Sphingolipids have important biological functions, and their role in human disease is only beginning to be appreciated. A deeper understanding of the sphingolipid system holds potential for the development of novel therapies for human disease.

Need for Further Study

  • How sphingolipid metabolism is regulated.
  • How altered sphingolipid metabolism causes disease.
  • How to treat patients with genetic disorders of sphingolipid metabolism.

Biography

  • NRSA Postdoctoral Fellow, NIDDK, 1981-1983, Advisor: Dr. Elizabeth F. Neufeld 
  • Ph.D., University of Texas Southwestern Medical Center, 1980
  • B.S., Bates College, 1976

Selected Publications

  1. Clarke BA, Majumder S, Zhu H, Lee YT, Kono M, Li C, Khanna C, Blain H, Schwartz R, Huso VL, Byrnes C, Tuymetova G, Dunn TM, Allende ML, Proia RL. The <i>Ormdl</i> genes regulate the sphingolipid synthesis pathway to ensure proper myelination and neurologic function in mice. Elife. 2019;8.

  2. Dunn TM, Tifft CJ, Proia RL. A perilous path: the inborn errors of sphingolipid metabolism. J Lipid Res. 2019;60(3):475-483.

  3. Kono M, Conlon EG, Lux SY, Yanagida K, Hla T, Proia RL. Bioluminescence imaging of G protein-coupled receptor activation in living mice. Nat Commun. 2017;8(1):1163.

  4. Proia RL, Hla T. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest. 2015;125(4):1379-87.

  5. 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.


This page was last updated on October 15th, 2020