Richard Leonard Proia, Ph.D.

Senior Investigator

Genetics & Biochemistry Branch

NIDDK

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

+1 301 435 6504

richard.proia@nih.gov

Research Topics

Our primary aim is to understand the normal and pathological roles of sphingolipids and to develop effective therapies for diseases related to sphingolipid metabolism.

Current Research

Sphingolipids, named after the enigmatic Sphinx of Greek mythology due to their mysterious properties, play a crucial role in cellular biology. They are essential components of cell membranes and also act as signaling molecules that regulate key functions within the vascular, nervous, and immune systems.

Sphingolipid metabolism is implicated in several human diseases, most notably in a group of inherited lysosomal storage disorders. These disorders, characterized by impaired degradation of sphingolipids, often lead to rare neurodegenerative conditions. Notable examples include Tay-Sachs disease, Sandhoff disease, Gaucher disease, Fabry disease, Krabbe disease, Farber disease, and GM1 gangliosidosis. Moreover, gene defects affecting sphingolipid metabolism have been linked to more common neurodegenerative disorders, such as Parkinson's disease.

In our lab, we explore the functions of sphingolipids in both normal and diseased states through genetic approaches in mice and in patient cells. Our ultimate goal is to develop therapeutic strategies for sphingolipid metabolism disorders.

Applying our Research

Understanding the biological functions of sphingolipid metabolism is crucial, as its significance in human disease is increasingly recognized. Gaining deeper insights into sphingolipid metabolism holds promise for the development of innovative treatments for various human diseases.

Need for Further Study

  • Elucidating how altered sphingolipid metabolism leads to disease.
  • Developing effective treatments for patients with sphingolipid metabolism disorders.

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. Duffy HBD, Byrnes C, Zhu H, Tuymetova G, Lee YT, Platt FM, Proia RL. Deletion of GBA in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model. JCI Insight. 2024.
  2. Allende ML, Lee YT, Byrnes C, Li C, Tuymetova G, Bakir JY, Nicoli ER, James VK, Brodbelt JS, Tifft CJ, Proia RL. Sialidase NEU3 action on GM1 ganglioside is neuroprotective in GM1 gangliosidosis. J Lipid Res. 2023;64(12):100463.
  3. Zhu H, Byrnes C, Lee YT, Tuymetova G, Duffy HBD, Bakir JY, Pettit SN, Angina J, Springer DA, Allende ML, Kono M, Proia RL. SARS-CoV-2 ORF3a expression in brain disrupts the autophagy-lysosomal pathway, impairs sphingolipid homeostasis, and drives neuropathogenesis. FASEB J. 2023;37(5):e22919.
  4. Kono M, Hoachlander-Hobby LE, Majumder S, Schwartz R, Byrnes C, Zhu H, Proia RL. Identification of two lipid phosphatases that regulate sphingosine-1-phosphate cellular uptake and recycling. J Lipid Res. 2022;63(6):100225.
  5. 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.

Related Scientific Focus Areas

This page was last updated on Thursday, November 7, 2024