Qiaobing Xu
Tufts University, MA·Biomedical Engineering
One way to treat disease is to destroy a harmful protein rather than just block it. PROTACs (proteolysis-targeting chimeras) are molecules that do this.
- Fields
Biomedical Engineering
Pharmacology
Chemistry
- Topics
targeted protein degradation
E3 ubiquitin ligase
ubiquitin-proteasome system
- Grants
- 1 known grant, through Jul 2030
What they work on
- Covalently attach a ligand that binds the target protein onto an E3 ligase-related protein, creating a two-part degrader that avoids the PROTAC hook effect.
- Deliver pre-fused E3P:PROTAC complexes inside cells using lipid nanoparticles (LNPs) and measure target protein degradation in cells and in animals.
- Test whether LNP-delivered PROTAC systems that degrade BRD4, a gene-regulating protein, can reverse liver fibrosis in a mouse model.
More about the research
They hold a target protein next to an E3 ligase, an enzyme that tags proteins for destruction by the cell's disposal machine, the proteasome. This requires three parts to come together at once. At high doses, though, PROTAC molecules can bind the target or the E3 ligase separately without joining all three. This drop in activity, called the "hook effect," makes choosing doses in clinical studies difficult.
Why it matters
More efficient targeted protein degradation could give a new way to treat diseases including cancer and liver fibrosis. Avoiding the hook effect could make dosing simpler. Degrading BRD4 with nanoparticle-delivered degraders could lead to a new treatment for liver fibrosis.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
Mingxing Teng
Baylor College of Medicine, TX·Pharmacology
Build a comprehensive atlas of the cereblon interactome spanning canonical G-loop degron proteins, mutant G-loop variants and hidden non-G-loop targets, extending bioinformatic predictions already covering 2,458 candidate proteins.
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.
The school
Tufts University: 19 labs on PI Pages, $278M a year on research, 144 research doctorates a year.
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