Welcoming Institute Scholar Rebecca Pinals to Sarafan ChEM-H
Rebecca Pinals has always been fascinated by very tiny things. The nanoparticles she studies are billionths of a meter in diameter and hundreds to thousands of times smaller than the width of a human hair. Their miniscule size endows them with special properties that can be engineered for a variety of functions, from light emission in television displays to delivery carriers for therapeutics.
Pinals recently joined Sarafan ChEM-H as an Institute Scholar and assistant professor of chemical engineering. She started out studying nanoparticles as an undergraduate, but it was during graduate school that she became enamored with understanding how nanoparticles interact with biological systems for use as sensors in medicine.
“Life’s most fundamental processes happen at incredibly small scales. By building equally tiny sensors, we can watch those processes as they occur; that’s the goal with nanoparticle-based sensing,” Pinals explained. “Often, we make a sensor that works very well in a simplified system. But when you send it into biology, biology is messy—it’s very complex—and our sensors fail.”
From chemical engineer to neuroscientist
Instead of being discouraged, Pinals saw this failure analysis as an opportunity to make better sensors. She is particularly interested in developing nanoparticle-based sensors, and eventually therapeutics, for neurodegenerative diseases like Alzheimer's disease, a disease to which she has a personal connection.
“For many of us, we have relatives who are suffering from various neurodegenerative diseases. Based on my experiences with my grandmother, I was very inspired to go specifically into Alzheimer's disease research. To me, it was such a frustrating disease. We just fundamentally have not figured it out yet,” said Pinals.
This motivated Pinals to venture into the field of neuroscience for her postdoctoral research. It was here that she began to merge her chemical engineering background with learning cutting-edge techniques for studying the brain.
“If you take a quantitative foundation and apply it to study a biological system, you look at the system differently. It’s a steep learning curve going into a new field, but having a fresh perspective and asking what seem to be the silly questions can end up being very important later on,” she said.
Then, when the opportunity arose to come to Stanford as a professor, Pinals knew it was the right fit.
“I was looking for a place that had a strong chemical engineering department, strong interdisciplinary and collaborative character, and a strong school of medicine. Stanford had all of those things,” she said. “So to discover that there was a special ecosystem at ChEM-H that had chemistry, engineering, and medicine all under one roof was just an incredible discovery, and it has been a great fit so far.”
Crossing the brain’s protective barrier
As she begins to build her independent laboratory, her research program focuses on building nanoparticle-based tools and models of the human brain to hopefully uncover the early dynamic changes that lead to neurodegenerative disease, as well as therapeutic strategies to treat diseases like Alzheimer’s. She is especially interested in a structure called the blood-brain barrier.
“I originally pictured the blood-brain barrier as the brain being a castle with the barrier being a moat surrounding it. But, the barrier is actually a beautifully integrated network of blood vessels throughout the brain. Each of these vessels has specialized junctions and transporters that filter for local delivery of nutrients to the brain, as well as clearance of waste,” Pinals explained.
The blood-brain barrier is challenging to get across, from a therapeutic standpoint. Drugs need to get across the barrier to treat diseases, but to keep you healthy, the barrier also must prevent harmful toxins from getting in. In Alzheimer's disease and other diseases, the barrier becomes leaky, disrupting the highly regulated exchange of waste and nutrients between the brain and bloodstream. Scientists still do not have a good grasp of the molecular basis for this leakiness and how the transport processes that control what can cross the barrier fail in disease.
Building nanoscale tools to study Alzheimer's disease
In order to study this problem, the Pinals lab uses three-dimensional models of the blood-brain barrier that they can build from human induced pluripotent stem cells, or iPSCs. In essence, they can take adult human cells and reprogram them into all the different cell types one would find at the blood-brain barrier, as well as encourage them to form the complex vascular brain structures of the human brain. In this highly controlled “blood-brain-barrier-on-a-chip” system, they are also able to generate Alzheimer's disease models and test out their nanoparticles in systems where they can evaluate specific genetic and environmental risk factors.
Her budding laboratory is so far composed of an initial cohort of chemical engineers, but Pinals is very excited to welcome trainees from bioengineering, neuroscience, biology, chemistry, and more, forming an interdisciplinary laboratory community over time. When asked what she is looking forward to about being a professor, she is most enthusiastic about working with and training the next generation of scientists.
“It’s been so fun already!” she said. “Working with students has been such a wonderful experience, with the ideas that they’re bringing to the table—the creativity and curiosity—and us being able to take those ideas and enact them in the lab. Setting students forth on their project and then seeing where the science takes them is very exciting!”
Rebecca Pinals is also a member of Bio-X.
