Vincent Tagliabracci
University of Texas Southwestern Medical Center, TX·Biochemistry
Many proteins in our cells look like enzymes but were long assumed to do nothing chemically. Pseudoenzymes are enzyme look-alikes thought to be inactive, and pseudokinases are the version of these that resemble kinases, the enzymes that attach phosphate groups to other proteins.
- Fields
Biochemistry
Pharmacology
Biology
- Topics
pseudoenzymes
pseudokinases
ether lipids
- Grants
- 3 known grants, through Apr 2030
What they work on
- Test whether mammalian ACAD10 and its related gene ACAD11 make ether lipids, building on the finding that ACAD10's kinase and phosphatase parts carry out missing steps of this pathway in C. elegans.
- Define how loss of ACAD10 lowers ether lipid levels and blocks the reuse of dietary ether lipids in mice, and how this affects cardiovascular and metabolic health.
- Determine whether the disease-linked pseudokinases SCYL1, SCYL2 and TBCK catalyze chemical reactions, using purified proteins, biochemistry and mass spectrometry.
- Test whether the active sites of SCYL1, SCYL2 and TBCK are needed to keep the Golgi, protein trafficking and cell growth normal, using switchable knockdown cell lines rescued with normal or mutant proteins.
- Find the target proteins and new modifications of pseudoenzymes from several enzyme superfamilies using SidBait, the lab's proximity-ligation method for capturing enzyme-substrate interactions.
More about the research
The lab's grants describe work showing that some of these proteins do carry out reactions, only different ones from their active relatives. They also describe enzymes found in unexpected places. The projects ask what chemistry these overlooked proteins perform and how that chemistry matters for health. One project studies a specific enzyme in fat metabolism. Another studies pseudokinases linked to rare brain diseases. A third broadly searches for hidden activities across enzyme families.
Why it matters
Lower blood plasmalogen levels are seen in aging, coronary artery disease, Alzheimer's disease and type 2 diabetes. Identifying the enzymes that build and recycle ether lipids could therefore guide treatments aimed at these fats. Working out whether SCYL1, SCYL2 and TBCK act as enzymes could explain how rare neurodevelopmental and neurodegenerative disorders arise and suggest therapeutic strategies. More broadly, finding the activities of pseudoenzymes may eventually lead to new diagnostics or treatments.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
David Pagliarini
Washington University in St Louis, MO·Biochemistry
Determine the chemical reactions catalyzed by ACAD10 and ACAD11, two enzymes that prepare 4-hydroxy fatty acids for fat burning, and test whether their kinase domain adds a phosphate group at the 4-hydroxy position, using enzymology and structural biology.
Cuong Q Nguyen
University of Florida, FL·Microbiology & Immunology
Catalog chemically modified peptides in salivary glands from Sjögren's disease mouse models and patients, using ultrasensitive deep proteome profiling with high-resolution proteomics.
Mark Chance
Case Western Reserve University, OH·Biochemistry
Provide proteomic and small-molecule analysis to cancer investigators, including protein identification, post-translational modification characterization, quantitative proteomics, protein interactome mapping and metabolomics, across collaborative and high-throughput service modes.
The school
University of Texas Southwestern Medical Center: 40 labs on PI Pages, $869M a year on research, 86 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.