Jaewon Chang
Emory University, GA·Chemistry
Most drugs work by sticking to a protein and blocking it, which means the protein has to have a pocket a small molecule can grab. A newer strategy sidesteps that requirement: instead of blocking the protein, destroy it.
- Fields
Chemistry
Biochemistry
Pharmacology
- Topics
targeted protein degradation
degraders
E3 ubiquitin ligase
- Grants
- 1 known grant, through Jul 2028
What they work on
- 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.
- Build two-headed degrader compounds by linking these warheads to established ligands for model proteins, JQ1 for BRD4 and SLF for FKBP12, and screen them in cells for induced target degradation.
- Confirm that lead compounds work through the intended route by showing they cause ubiquitination and proteasomal degradation of their target proteins.
- Identify which E3 ligases the active degraders covalently attach to, using chemoproteomic mass spectrometry across the whole proteome, and validate them as new recruiters for targeted protein degradation.
More about the research
Targeted protein degradation uses small molecules called degraders that act as molecular matchmakers, physically tethering a disease-causing protein to one of the cell's own disposal enzymes, an E3 ubiquitin ligase, which tags the protein for destruction by the proteasome, the cell's shredder. The catch is that the human genome encodes more than 600 E3 ligases, but nearly all published degraders recruit just two of them, cereblon and VHL. Chemistry here aims to expand that toolkit by finding small molecules that latch onto previously unused E3 ligases.
Why it matters
Many disease-driving proteins have no pocket for a conventional drug to bind, leaving them untreatable by inhibitors. Widening the set of E3 ligases that degraders can recruit would give medicinal chemists more ways to destroy such proteins, and because different E3 ligases are abundant in different tissues, it could eventually enable degraders that act where they are needed and spare other tissues.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
Qiaobing Xu
Tufts University, MA·Biomedical Engineering
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.
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
Emory University: 70 labs on PI Pages, $1.2B a year on research, 286 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.