Richard Leonard Proia, Ph.D.

Senior Investigator

Genetics & Biochemistry Branch

NIDDK

Building NIHBC 10 - Clinical Center, Room 9D06
10 Center Dr
Bethesda, MD 20892

+1 301 435 6504

richard.proia@nih.gov

Research Topics

To understand how sphingolipids function normally and during diseases, and to develop therapies for the the diseases of sphingolipid metabolism.

Current Research

Sphingolipids, the topic of our research, were named after the 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. Sphingolipids also function directly as signaling molecules regulating basic functions in the vascular, nervous, and immune systems.

Sphingolipid metabolism is 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, and in most cases, neurodegenerative disease. These lysosomal storage disorders include Tay-Sachs disease, Sandhoff disease, Gaucher disease, Fabry disease, Krabbe disease, Farber disease and GM1 gangliosidosis. Gene defects affecting sphingolipid metabolism have also been linked to the more common neurodegenerative disorder, Parkinson's disease.

In our lab, we 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

Sphingolipid metabolism has important biological functions, and its role in human disease is beginning to be appreciated. A deeper understanding of the sphingolipid metabolism holds potential for the development of novel therapies for human disease.

Need for Further Study

  • How altered sphingolipid metabolism causes disease.
  • How to treat patients with 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 Ormdl 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. 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

This page was last updated on Wednesday, August 17, 2022