The name of this compound is currently a secret, so for now we’ll call it the “Chelsea.” But if further studies pan out, the whole world might someday learn about a promising new drug treatment for Alzheimer’s disease.
“Our lab has discovered anti-Alzheimer’s properties in several small molecules from natural sources such as corn silk and soybeans,” says Chelsea Miller, a PhD student in the lab of Qing X. Li in the Dept. of Molecular Biosciences and Bioengineering. “My hypothesis is that their mechanism of action is the direct binding and inhibition of an enzyme called GSK3-beta.”
Before she targeted GSK3 and discovered the soybean compound, Chelsea was a local girl who earned her BS in materials science and engineering at U of Arizona, then her MS in bioinformatics at Johns Hopkins. But she missed home and decided to pursue her PhD at UH – switching to bioengineering, with a focus on Alzheimer’s research.
“I really like to tackle challenging puzzles and problems, and Alzheimer’s is such a devastating disease; my grandmother had it, and it was really hard to witness her decline,” she says. “We still don’t know much about this very complex disease, so for personal and professional reasons, I hope to crack at least part of the puzzle.”
Starting with GSK3 – known to be linked to the progression of Alzheimer’s – Chelsea searched the literature and found a relatively obscure, naturally occurring chemical in the heterocyclic family that potentially targets Tau tangles in the brain.
“GSK3 is overactive in Alzheimer’s patients, so a holy grail of research is to restore normal activity levels of GSK3 in order to slow the disease progression,” she explains. “So we thought to give the heterocyclic chemical a try and, amazingly, it inhibited the enzyme! Even after all the hard work and eyestrain, it felt like a lucky or serendipitous discovery.”
Since summer 2021, Chelsea has conducted inhibition assays to determine a dose-response relationship between the compound and GSK3. She’s also using bioluminescence resonance energy transfer (BRET) to measure their interactions inside human neuroblastoma cells.
“My project is to prove without a doubt that this compound directly binds with GSK3, and the initial results have fueled my interest and enthusiasm even more,” she says. “Drug development is a long process, and although it’s a longshot to find a cure for Alzheimer’s, I’m hopeful this is one small step in the right direction.”
Photo: Chelsea crunches the data with MBBE student Shaina Young.