- Deputy Chief: Genetics & Biochemistry Branch
- Section Chief: Genetics of Development and Disease Section, Genetics & Biochemistry Branch
- Director: Mouse CRISPR/Cas9 Genome Editing Facility, Cores & Support Services
- 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
To understand how sphingolipids function normally and during diseases, and to develop therapies for the the diseases of sphingolipid metabolism.
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.
- The Ormdl genes regulate the sphingolipid synthesis pathway to ensure proper myelination and neurologic function in mice.
- 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.
- Elife (2019 Dec 27) 8. Abstract/Full Text
- A perilous path: the inborn errors of sphingolipid metabolism.
- Dunn TM, Tifft CJ, Proia RL.
- J Lipid Res (2019 Mar) 60:475-483. Abstract/Full Text
Research in Plain Language
Our lab studies the metabolism of sphingolipids, lipid molecules that form cell membranes and transmit signals to cells. When sphingolipid levels are disrupted, neurodegenerative diseases may result. Sphingolipid metabolism diseases include Tay-Sachs disease, Sandhoff disease, Gaucher disease, Fabry disease, Krabbe disease, Farber disease and GM1 gangliosidosis. The more common neurodegenerative disorder, Parkinson's disease, is also linked to defects in sphingolipid metabolism. Our work is aimed ultimately at devising treatments for the sphingolipid metabolism diseases.