Turning Biology into Better Skin Care
Dermatologist Christopher Bunick, MD, PhD’s fascination with science started long before he arrived at Yale Medicine. “It started in junior high school,” he recalls, “with a science fair project about growing crystals and mimicking the microgravity in space.”
More than 30 years later, in his own lab at Yale School of Medicine, Dr. Bunick is still exploring the unique structures of crystals. He says the answers he finds could help unlock some of biology’s biggest—and smallest —questions. “I’m driven by the need to help people,” he says, “but also the need to understand how to help people at a molecular level.”
One priority for the Bunick Lab is studying eczema, also known as atopic dermatitis, which affects up to 10% of Americans. Eczema’s red, itchy rashes damage the protective barrier of your skin, which in turn drives more inflammation. “So many of the skin conditions in dermatology become a vicious cycle between skin barrier disruption and inflammation,” says Dr. Bunick, who also an associate professor of dermatology at Yale School of Medicine.
Researchers say breaking the cycle means taking a close look at how that barrier works. Here, Dr. Bunick explains how his team is thinking small to tackle some of the biggest problems in dermatology.
At the microscopic level, how does eczema affect our skin?
The skin is really a window. When we think of inflammatory skin disorders, that skin barrier really is the first line of defense protecting the whole body as well as that skin from inflammation.
In eczema, we see a disruption of the skin barrier that allows two things to happen. It allows more irritants, like all the chemicals we’re exposed to in the world, to penetrate the skin and drive more inflammation, but it will also increase the chance for infection. So, when you have those microscopic fissures in the skin barrier, it allows bacteria and viruses and infectious organisms to get in.
My job as the scientist is understanding how to break this cycle. How do we intervene, both to stop the inflammation and to repair that skin barrier, this critical interface between our bodies and the infectious, chemical world that we live in?
What we call atomic resolution dermatology is really trying to capture how the human skin is working at the level of atoms and bonds, and how medications might be working on those structures to, for example, improve the skin barrier. We’re all hearing about precision medicine and tailored therapies to individualize people. And having this molecular understanding of dermatology allows us to enter that precision medicine era with more knowledge.
What is X-ray crystallography, and how is it helping to discover new treatments?
X-ray crystallography is a technique that allows you to really examine the atomic level structure of proteins, nucleic acids and their potential interactions with, for example, medications.
When you take a very pure protein, concentrate it down and put it in just the right conditions, it forms a crystal. And that crystal is a perfectly aligned lattice of lots and lots of molecules of that protein of interest. And then when you shine or hit that crystal with a very focused beam of X-rays, that crystal then diffracts the light.
Picture a diamond—if you take that diamond and you shine light on it the right way, you see that light diffract into all those little dots. That’s exactly what we’re doing with X-rays, but it’s the protein that’s directing that X-rays as opposed to the carbon atoms in the diamond.
And then we use math to take those dots, take that pattern, and turn it into a 3D model of the protein at that very small, atom-and-bond level so we can ask those critical questions, such as, “What does this molecular structure tell us about helping the human patient?”
As long as a treatment works, do I really need to understand how it works?
As a practicing clinician that sees almost 5,000 patients a year, it’s very important to me that patients understand the medicines I’m prescribing.
More importantly, we can serve our patients better if we actually understand how the drugs we’re prescribing work at a molecular level, so we can explain how they’re different from other therapeutics indicated for a certain disease, and what the structural properties of those drugs mean in terms of efficacy and safety.
It’s about connecting the bench where we do the science to the bedside where that science is helping people. It’s about translating the science of the therapies to the administration of the therapies in a patient centered, evidence-based way. Combining those—being able to help patients while also thinking from a molecular perspective—is what drives me every day.
