Juan Hu
San Diego State University, CA·Chemistry·Early-career
Many disease-driving proteins work by sticking to other proteins, and these contact surfaces are notoriously hard to block with ordinary small-molecule drugs. Cyclic peptides, short amino-acid chains closed into a ring, are large enough to cover such surfaces, which makes them attractive candidates against targets considered "undruggable." Their drawback is delivery: because they are bigger and more structurally complex than typical oral drugs, they usually cross cell membranes poorly, so they fail both as medicines and as tools for experiments inside living cells.
- Fields
Chemistry
Biochemistry
Pharmacology
- Topics
cyclic peptides
macrocycles
membrane permeability
- Grants
- 1 known grant, through Nov 2027
What they work on
- Screen DNA-encoded combinatorial libraries, in which each compound carries an identifying DNA barcode, with a droplet-scale permeation assay to find cyclic peptides that efficiently cross membrane bilayers.
- Validate permeable macrocycle hits from library screening using the cell-based permeation assay developed by the lab, and further refine that assay as a general tool for measuring entry into cells.
- Apply machine learning to the large screening datasets to identify structural features that govern permeability, focusing on molecules beyond the Rule of 5 that fall outside standard drug-likeness guidelines.
- Build empirical models of the pharmacokinetic behavior of macrocyclic peptides so that non-Lipinski molecules can be designed and advanced toward therapeutic and diagnostic use at scale.
More about the research
Occasionally one crosses unusually well, but nobody knows the rules, largely because there has been no way to measure membrane crossing for many molecules at once.
Why it matters
Blocking protein-protein interactions could reach disease targets that current small-molecule drugs cannot touch, but cyclic peptide candidates stall because they rarely enter cells. Measurement tools and data-driven rules for predicting which ring-shaped peptides cross membranes could help chemists design these molecules deliberately rather than by luck, supporting development of new therapeutics, diagnostics, and laboratory probes for studying proteins inside living cells.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Robert Lokey
University of California-Santa Cruz, CA·Chemistry
Determine how far side chains can shield polar backbone atoms of a macrocyclic peptide inside a membrane, and conversely how much polar side-chain chemistry can be carried across by interacting with the backbone.
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.
Steven Van Lanen
University of Kentucky, KY·Pharmacology
Develop and run virtual screens — target-based, pharmacophore-based and machine-learning-based — to prioritize compounds for center projects before any laboratory testing.
The school
San Diego State University: 13 labs on PI Pages, $182M a year on research, 142 research doctorates a year.
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