Stefanka Spassieva
University of Kentucky, KY·Neuroscience
Sphingolipids are a family of fats built into cell membranes, and the brain depends on making them correctly. When enzymes in this pathway are broken, people develop severe neurological disorders such as sphingolipidoses and hereditary neuropathy.
- Fields
Neuroscience
Biochemistry
- Topics
sphingolipids
sphingolipid metabolism
ceramide synthase 1
- Grants
- 1 known grant, through May 2030
What they work on
- Test whether high brain levels of sphingoid bases and their phosphates in CerS1-deficient mice change gene activity in neurons and glia over time, disrupting neuronal maturation and differentiation.
- Test how CerS1 deficiency and excess sphingoid bases in neurons alter the movement of internal membranes and lipids, using CerS1 mutant and CerS2-rescued transgenic mice and in vitro systems.
- Test whether sphingoid base phosphate signals made by neurons, such as sphingosine-1-phosphate, activate glia, the brain's support cells, contributing to neurodegeneration.
More about the research
A central enzyme is ceramide synthase 1 (CerS1), the main version in neurons, which makes ceramide, the shared starting material for all sphingolipids. Loss of working CerS1 in humans and mice causes epilepsy with intellectual disability and degeneration of the cerebellum, the brain region that coordinates movement. The team's earlier work showed that the damage comes from a buildup of sphingoid bases (sphingosine and dihydrosphingosine) and their phosphate forms. These molecules are also raised in Alzheimer's disease, yet how they harm neurons is unknown.
Why it matters
Buildup of sphingoid bases damages neurons in CerS1 deficiency, and these molecules are also elevated in Alzheimer's disease. Learning how they harm neurons and activate glia could point to steps that might be targeted in inherited sphingolipid disorders, ataxia, epilepsy and more common neurodegenerative diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Bumsuk Hahm
University of Missouri-Columbia, MO·Microbiology & Immunology
Determine how influenza virus lowers S1P lyase (SPL), the enzyme that degrades the lipid messenger S1P, and raises sphingosine kinase 2 (SK2), which makes it, and how these shifts speed viral replication in infected cells.
Stefan Worgall
Weill Medical College of Cornell University, NY·Medicine & Clinical Research
Measure sphingolipid production in children with asthma during and after rhinovirus-triggered asthma attacks, using sphingolipid levels in nasal fluid and blood and gene activity in nasal cells.
Yekaterina Zaytseva
University of Kentucky, KY·Medicine & Clinical Research
Determine whether FASN overproduction in colorectal cancer cells, through the exosomes they release, turns liver hepatic stellate cells into tumor-supporting fibroblasts, using genetic changes and the FASN inhibitor TVB-2640.
The school
University of Kentucky: 34 labs on PI Pages, $528M a year on research, 319 research doctorates a year.
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