When the average American thinks about Botox, they imagine injections that deliver wrinkle-free foreheads and migraine relief. When Rongsheng Jin, Ph.D., professor in the Department of Physiology and Biophysics from UC Irvine’s School of Medicine, thinks about Botox, he recalls the deadly toxin it was derived from, its intricate three-dimensional structure first determined by his team and the mechanisms that can both prevent the appearance of wrinkles and kill humans.
The bacterium responsible for Botox, Clostridium botulinum (C. botulinum), and another deadly bacterium, Clostridioides difficile (C. diff), are the two main research areas of focus for Jin. In his lab, Jin and team uncover the blueprints behind these bacteria and the toxins they produce to better understand them and find ways to use their own mechanisms for good — such as improved cosmetics or potential cancer therapeutics — and to combat their deadly effects.
“We focus on the mechanism,” said Jin. “Knowing and understanding the mechanism at the molecular level is the universal approach. Once you know the blueprints of how it works, you can do so many things — you can make it better or worse.”
Jin’s lab has made significant strides in finding ways to combat C. diff infections — a Centers for Disease Control and Prevention urgent threat — which are typically contracted in hospitals and healthcare settings and has symptoms ranging from diarrhea to life-threatening colitis. One approach pursued in the Jin lab is a novel vaccine that can prevent infections and the other is a protein therapeutic that essentially tricks the toxin into binding to the drug rather than the human receptors. The latter of the two is available for licensing through UCI Beall Applied Innovation’s Research Translation Group.
On the C. botulinum front however, a vaccine will likely never happen.
“There will be no chance to develop a vaccine for this toxin because nobody is going to take it,” said Jin. “If you take the vaccine, Botox doesn’t work!”
In light of this, Jin and team have shifted their focus from a C. botulinum vaccine to exploring the use of novel antitoxins to treat infections rather than prevent them or to develop new products with improved clinical and cosmetic features.
Jin makes clear that fully understanding how a bacterial toxin looks and operates within the human body is critically important. To illustrate that point, Jin and team are currently in the early stages of exploring the use of a fragment of the deadly C. diff toxin as a cancer treatment or using C. botulinum toxin’s own tactics to develop better and safer cosmetics.
“We focus on the mechanism and then we ask two questions,” said Jin. “‘Is there anything good about this toxin that we can learn from?’ and ‘How to play on a pathogen’s weakness to defeat it?’”
Learn more about Jin and his research.
Main photo and image courtesy of Rongsheng Jin, Ph.D.