Some research journeys begin in the lab with a spark of an idea or an unexpected discovery. For Yong Xu, MD, PhD, the road that recently led the distinguished scientist to USF Health took root decades ago under the loving guidance of his grandfather.
That close relationship would ultimately put Dr. Xu on a path to his cutting-edge work today studying the interplay between nutrition/metabolism and a wide range of neurobiological disorders, such as dementia, depression and more.
“In my neighborhood, all the adults seemed to be doctors or nurses or work in the medical field,” he said.
In fact, Dr. Xu’s parents each worked at a hospital — his father as an administrator and mother a pharmacist, and his grandfather spent most of his career as a hospital administrative manager. Not surprisingly, from a very young age, Dr. Xu envisioned working in a hospital as a physician. And he pursued that dream, earning his medical degree and then starting on a master’s degree to specialize in gastroenterology.
But then came a tragic turn that changed everything. His grandfather was diagnosed with esophageal cancer. The news hit Dr. Xu hard. He had grown up sharing a room with his grandfather, and they shared a close bond as well. It pained him to witness his grandfather’s slow, agonizing demise — yet that became the catalyst to turn his career in a new direction.
“At first, when he was diagnosed, I thought what I learned in GI medicine could be very helpful,” he said. “But I soon realized I was helpless and hopeless. And that’s when I realized that even a clinical physician knows so little about fundamental science, human biology and disease. We can provide a diagnosis, but sometimes we can’t even do that.
“So that’s when I realized that maybe there was a new path for me,” Dr. Xu said. “I had a new vision to study human biology, so one day I could be more helpful and hopeful for our patients.”
Dr. Xu altered his course and moved to Canada to earn his PhD from the University of Alberta in cell biology and neuroscience. After completing his training, he headed south in 2006 to the University of Texas Southwestern Medical Center for post-doctoral training in neuroendocrinology. There he spent four years studying how the brain regulates feeding and metabolism.
Four years later, Dr. Xu moved to the Baylor College of Medicine in Houston to begin his research career, getting promoted to professor in 2020 while also serving as associate director of Baylor’s Children’s Nutrition Research Center, with an intense focus initially on obesity and diabetes.
At Baylor, he immersed himself in research to identify novel neural circuits, neurotransmitters and signals that are crucial for coordinating control of body weight, glucose balance and the web of cues, needs and rewards known as “feeding behavior” – why, when and what we eat.
At first, Dr. Xu viewed himself as a neuro-endocrinologist, but his focus expanded over the next 14 years as a neuroscientist to include a wide range of conditions, such as dementia, anxiety, motion sickness, drug abuse, ADHD, delayed puberty, postpartum-depression, breast cancer and heart diseases.
“If you want to criticize me, I guess you could say that I don’t have only one focus,” he said, smiling. “I have a very broad research interest and I’m driven by curiosity as well as the potential for clinical impact.”
At Baylor, Dr. Xu’s developed several long-standing collaborations with physicians who would contribute knowledge about genetic variants associated with certain human diseases. Dr. Xu and his team were able to identify three novel genes tied to obesity, leading to greater understanding of what types of medicine can be an effective treatment.
“Our work also resulted in new patents that may one day become new medicine for patients,” he said.
His efforts continue in that varied realm at USF Health, where he is building a new Center for Molecular Psychiatry in the Department of Psychiatry & Behavioral Neurosciences. This field explores the biological elements underlying psychiatric disorders and treatments. His goal is to have 25 to 30 people working in the center by year’s end.
“My early training in clinical medicine and later training in basic neuroscience has had a profound impact on my vision as a scientist and basically shaped how I pursue and build up my research program,” Dr. Xu said. “To put it simply, I am a basic neuroscientist with a physician’s mind. I want to advance the science that could make a difference in clinical practices. I do scientific research if it can make a difference in clinical medicine, for our patients.”
Today, Dr. Xu’s driving interest continues to be the interplay between nutrition/metabolism in connection to a range of neurobiological disorders. In the process, he and his team discovered a link between obesity and Alzheimer’s disease.
“We started by looking at how the brain regulates the neurocircuit and behavior,” he said. “There are many, many behaviors that are important for survival — and feeding behavior is fundamental because it is essential for the continuation of an individual. After studying feeding behavior for a number of years, we began to realize that it can influence all the other behaviors. Basically, these behaviors are more or less influenced by the nutrition signals.”
That led, by chance, to understanding a connection between feeding behavior and Alzheimer’s. Dr. Xu and his team’s research in this area is now funded by the National Institutes of Health. Their move in this direction stemmed from a study into obesity with particular patients who carried a certain gene mutation. They mimicked that mutation in the lab and hit upon an unexpected revelation. The mutation seemed to have an effect on cognitive testing as well.
Dr. Xu relayed the results to a clinical collaborator working with the patients.
“We said, ‘Hey, we found this correlation, you may need to look at this with your patients. They did — and found that the patients did indeed have a decline in memory. They basically confirmed that this gene mutation can not only cause weight gain but also memory decline in people.”
Specifically, Dr. Xu and his colleagues concluded that a gene mutation causes the loss of function of a brain receptor. That prompted them to ask: Was there a pharmacological solution to activate the receptor and help improve memory?
Another test was then performed with Alzheimer’s amyloid pathology and the result was encouraging. An agonist molecule for the receptor improved memory.
“Based on this, we developed a proposal that has fortunately been funded by NIH, and now we are continuing to explore this direction,” he said. “And we’ve expanded to look at other types of Alzheimer models.”
“This is how we got here,” Dr. Xu said. “Now we realize there is a fundamental interaction between the nutrition/metabolism and many neurobiological behaviors or diseases,” he said. “Hopefully this will give us a handle for prevention or diagnosis of not only metabolic problems but neurobiological problems.”
As for Dr. Xu, what got him here was the grandfather he loved — and the relentless research drive that fueled his career after losing him.
— Photos by Ryan Rossy, USF Health Communications