Natasha O’Brown receives early career award for work on blood brain barrier
In the lab of Natasha O'Brown, researchers study the brain of zebrafish for insights into human health.
If you can imagine your brain as an exclusive nightclub, then it’s the bouncer standing guard at the door that most intrigues Rutgers scientist Natasha O’Brown.
Her research explores the blood-brain barrier, a network of cells that regulates what can enter the brain—a complex process that promotes healthy brain function but also creates obstacles for medical treatment.
Natasha O'BrownO’Brown’s work in this emerging area of life science was recognized earlier this year when she was named a Freeman Hrabowski Scholar by the Howard Hughes Medical Institute (HHMI) – an honor that provides up to 10 years of support for early career faculty who show the potential to become leaders in their fields.
O’Brown, a professor in the Department of Cell Biology and Neuroscience in the School of Arts and Sciences, is the first Rutgers faculty member to receive HHMI support in more than a decade.
In the interview below she breaks down the blood brain barrier.
What is the blood-brain barrier? Does everyone have one?
Yes, everything from fish to humans has a blood-brain barrier. It’s created by the blood vessels in your brain which have these specialized properties that keep them very restrictive.
You can think of the brain as this VIP club and the barrier as the bouncer who’s controlling what is getting in and what’s getting out. It’s not a complete wall, but it’s highly selective, like a filtering process. And it’s absolutely necessary for maintaining everything you need for day-to-day human functioning.
What is the connection between the blood-brain barrier and illnesses such as Alzheimer’s and Parkinson’s?
Barrier breakdown has been implicated in almost every neurodegenerative disease, including Parkinson’s, Alzheimer’s, multiple sclerosis and ALS. But the barrier breaks down in different areas of the brain, with different neurons that are susceptible for each of these diseases. How that’s actually happening is one of the areas my lab is trying to tackle. Where is this heterogeneity coming from? Why are certain neurons most susceptible for one disease versus another disease?
How does the blood-brain barrier, despite its vital protective function that you just described, hinder medical treatment?
It is a huge obstacle to drug delivery. Ninety-eight percent of drugs that are currently available and, on the market, cannot get into the brain because of the BBB. It’s especially devastating for brain tumors. Advances for glioblastoma (a type of brain cancer), for example, have not been made in the last three decades, because treatments can’t get into the brain at effective doses. It is also a huge barrier for psychiatric medicine. Something that might work in a dish isn’t actually going to work in a body because you have this barrier that is protecting and preventing these molecules from getting in.
Does your lab explore both of these aspects: Helping the barrier stay strong, and also trying to understand how to allow passage for critical medication?
It is both. I am a developmental biologist at heart, so one focus is understanding how the barrier is initially built. Yes, it’s a property of these blood vessels but it’s something that’s embryonically established and actively maintained throughout your life by signals from the surrounding cells in the brain. These signals are constantly saying: “you’re a blood vessel in the brain, stay tight!” Yet we still know very little about which cells or signals are being used to send that message.
So, we want to understand how the barrier is built during development, so we can identify ways to open the barrier transiently and tighten a leaky barrier. Right now, my lab is in the process of screening for small molecules that can open a barrier transiently, so that we may finally be able to improve treatment options for brain tumors.
Your lab uses zebrafish as models for your research. How are they useful?
They are amazing tropical fish! They are not that big. The adults are a couple of inches. The embryos are the size of an eyelash. They develop rapidly and externally and are transparent so you can use them for live imaging. We can get the entire brain when we’re imaging them on a microscope.
You have been named an HHMI scholar this year. What does that mean for your work? Are there specific projects you will be working on?
Unlike federal funding, where you have to have a very specific hypothesis, and preliminary data, the HHMI program is funding me and my ideas. It allows us to follow the thread wherever we want to go with it. The fact that we are planning on doing genome-wide screenings to identify any gene in any cell that affects the barrier—that would never be (federally) funded. HHMI is saying: “Sure, this is bold and risky, but you could identify something new.”
Your background is in evolutionary biology. It was during your post-doc at Harvard Medical School that you shifted gears to pursue the blood brain barrier. What made you want to change?
Part of the reason was to be more translatable. I lost my grandfather to Parkinson’s, so there are also personal reasons. I really liked the fact that in understanding the barrier, I could do it from an (evolutionary) biology standpoint, while also trying to come up with ways that could help patients.
I am not going to be the one to take it to the bedside, but with these new tools and an evolutionary approach, I think we can finally move past just managing symptoms—and start building real treatment strategies for brain diseases that have long lacked viable options, in large part because of the blood-brain barrier.
Natasha O'Brown, shown here with her research team, has been named a Freeman Hrabowski Scholar by the Howard Hughes Medical Institute , which will support her research into the blood-brain barrier.