By Darby Kendall
Bonnie Nagel, Ph.D., is the interim chief research officer and director of the Center for Mental Health Innovation at OHSU. At a recent talk she gave, Nagel highlighted the work of three uniquely different researchers and discussed how their powerful work fuels new interventions, drugs and policies.
Here are the highlights from Nagel’s talk, where she weaves these stories of breakthrough discovery into a human-centered look at how science at OHSU touches patients, families and communities.
Transcript
Have you ever wondered what’s happening in your body when things don’t feel quite right? Have you ever sat at a doctor’s office or stood in line at a pharmacy and thought, “How does this medication that I’m getting prescribed actually work, and why does it work for some people but not for others?”
Somewhere right now someone is asking those very same questions. A man getting ready for work, getting ready to face another day with chronic pain; a teenager whose depression hasn’t responded to three different medications; a woman navigating menopause with no one to explain her options. In each case, the plea is the same: There has to be something to make things better.
Dr. Bonnie Nagel is the interim chief research officer and director of the Center for Mental Health Innovation at OHSU. At a recent talk she gave, Dr. Nagel highlighted the work of three uniquely different scientists at OHSU and discussed how their research fuels new interventions, drugs, and policies. Here are the highlights from her talk.
What separates suffering from solution is not luck; it is understanding, and understanding inherently comes through science. That understanding does not arrive fully formed. It actually begins very quietly in the labs of places like OHSU. When structural insight meets therapeutic design meets real-world implementation, something very powerful happens. It’s the full arc of scientific translation.
Imagine sitting across from someone you love and watching them have a seizure, or getting up each day with pain that just never seems to stop. In those moments, something very small is happening. Tiny gates in the brain are opening and closing at the junction between two neurons, the place we call a synapse. One cell releases a chemical messenger, an important one of which is called glutamate. The next cell receives that signal through microscopic receptors. Your brain works because billions of these tiny gates open and close in perfect balance, but when the balance tips, the consequences can be pretty profound. Too much opening can trigger seizures. Too much sensitization can amplify chronic pain. For decades, medicine has tried to help by targeting these receptors, but here’s the humbling truth: We were designing treatments for gates that we really couldn’t see.
That’s what makes the work of OHSU neuroscientist Dr. Eric Gouaux so powerful. He and his team isolated these fragile receptor proteins. They collected millions of images using a cutting-edge cryo-electron microscope available at OHSU, and they assembled them into detailed three-dimensional structures down to individual atoms. For the first time, we could see the gates of the brain, and that changes everything. You can begin to create medications that stabilize a receptor without impacting the rest of the brain. You can reduce side effects. You can understand why some drugs help and others harm. Dr. Gouaux turned mystery into mechanism.
Let’s consider another example a little farther down the continuum. What many people don’t realize is that one of the molecules that helps with things like mood, motivation and thinking is something we actually usually think about with regard to metabolism, and that is thyroid hormone. Thyroid hormones influence how brain cells produce energy, form connections and maintain healthy signaling. Doctors have known for decades that if you give an individual thyroid hormone when regular antidepressants have not been working, sometimes it can help. The problem is that if you give the brain enough thyroid hormone to actually influence depression, you also affect the rest of the body. Heart rate speeds up, metabolism increases and bones can weaken over time.
That’s the challenge that Dr. Tom Scanlan at OHSU set out to understand. He looked at thyroid hormone and he asked, “What if we redesign the molecule so it reaches the brain efficiently, but speaks more selectively once it gets there?” His team began redesigning the hormone, changing its chemical structure so that it could cross the brain more efficiently and target specific receptor types more than others. And from there, a new treatment was developed. That’s the power of Dr. Scanlan’s discovery, which is now in phase two clinical trials. It didn’t start with a patient; it actually started with chemistry, but it ends with a person feeling hope. Hope that after years of struggling with dark depression, there might be a spark of light.
Our last story is at the other end of the translational continuum. For decades, menopause has been treated like a life stage for people to endure, not a physiological transition to understand more precisely. Hormones fluctuate dramatically, metabolism changes, bone density changes, cardiovascular risks emerge, and yet much of the guidance around hormone therapy has been shaped by incomplete data and generalized recommendations. This is where Dr. Alison Edelman and her team at the Center for Women’s Health at OHSU’s work becomes profoundly relevant. Her team studies hormones the way a cardiovascular researcher might study cholesterol by measuring them precisely and repeatedly. Hormonal medicine shapes decades of life. Hormone therapy can dramatically reduce symptoms, but dosing matters, delivery method matters and timing matters.
For years, women heard sweeping warnings or broad reassurances. Either hormones were very dangerous, or they were the solution to everything. Science is more nuanced than that, and Dr. Edelman’s work helps to refine that nuance. Menopause affects half the population for decades of life. It deserves the same rigor that we apply to any other major health transition. Dr. Edelman’s work at OHSU brings that rigor.
If you look at the work of doctors Eric Gouaux, Tom Scanlan and Alison Edelman, it might seem like three very different stories, but together they tell a single story. They reveal the full arc of science. The arc of science is not about a single breakthrough. It is about shortening the distance between understanding and well-being, and when that distance shrinks, lives change. That is the work of science at OHSU.
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