Angela Mabb
Georgia State University, GA·Neuroscience
Cells constantly tag proteins with a small protein called ubiquitin. The tag can mark a protein for destruction or change how it works.
- Fields
Neuroscience
Biochemistry
Genetics
- Topics
ubiquitination
deubiquitinase
E3 ubiquitin ligase
- Grants
- 1 known grant, through Aug 2029
What they work on
- Determine whether tagging of the deubiquitinase OTUD4 with ubiquitin by the enzyme RNF216 makes OTUD4 less stable, and whether the OTUD4 mutation found in Gordon Holmes syndrome makes the protein more stable.
- Test whether OTUD4 directly removes ubiquitin tags from the E3 ligase RNF216, and whether this changes RNF216's stability and its ability to attach ubiquitin to its target proteins.
- Determine in Gordon Holmes syndrome models whether overactive OTUD4 increases neuroinflammation and impairs reproduction, and whether reducing OTUD4 activity restores these functions.
More about the research
Other enzymes can trim or remove the tags. This tagging is essential for a healthy nervous system, and mutations in the tagging machinery cause several neurological disorders. Even so, how proteins in neurons gain and lose these tags is still poorly understood.
Why it matters
Gordon Holmes syndrome causes hormone problems, brain degeneration and dementia, and has no targeted treatment. By showing how overactive OTUD4 and faulty RNF216 disrupt nerve function, this work could point to new drug targets for GHS. It could also help with related conditions such as frontotemporal lobar degeneration, where OTUD4 levels are raised.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Michael James Emanuele
University of North Carolina at Chapel Hill, NC·Biochemistry
Define the wave of protein destruction occurring in G2 and at the G2-to-mitosis transition, determining which proteins are degraded and when, and how the phosphate-adding enzyme PLK1 controls this program, using proteomics and cell-based assays.
Jennifer Kong
University of Washington, WA·Biochemistry
Define the principles by which membrane-tethered E3 ubiquitin ligases, enzymes that tag proteins for destruction, recognize and target cell-surface receptors, mapping their target networks with mass spectrometry and biochemistry.
Jaewon Chang
Emory University, GA·Chemistry
Design and synthesize covalent warheads that react with lysine, tyrosine and serine residues on E3 ubiquitin ligases, the enzymes that tag proteins for destruction, going beyond the cysteine-reactive chemistry used so far.
The school
Georgia State University: 9 labs on PI Pages, $241M a year on research, 300 research doctorates a year.
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