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Tal Gilboa on Opening a Window into the Brain for Parkinson’s Diagnostics

The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as scientists, and their collaborations at the Wyss Institute and beyond. 

As Tal Gilboa watched the condition of her mentor and family friend diagnosed with Parkinson’s disease rapidly decline early in her biomedical engineering studies, she longed to apply her skills to develop a technology that would help similar patients. At the Wyss, she found that opportunity. Tal is now creating tools for Parkinson’s diagnosis and monitoring, which could accelerate drug development efforts. Learn more about Tal and her work in this month’s Humans of the Wyss.

What are you working on?

Tal Gilboa on Opening a Window into the Brain for Parkinson’s Diagnostics
Tal Gilboa, Postdoctoral Fellow. Credit: Wyss Institute at Harvard University

I’m developing methods to detect Parkinson’s disease early and monitor its progression to support drug development and clinical trials for new therapeutics for Parkinson’s and possibly other neurodegenerative diseases, like Alzheimer’s disease.

To do this, we’re combining two different technologies. First, we’re developing a way to isolate extracellular vesicles, or exosomes, that are released from the brain. Exosomes are particles bound by a lipid bilayer that are released from almost all types of cells. These vesicles sample biomarkers from neurons in the brain and preserve them in their original context. We are developing technologies to isolate the exosomes of interest from a blood sample.

Then, we use a second technology to quantify specific proteins inside the exosomes at the single molecule level, like pathological alpha-synuclein species, that are related to Parkinson’s disease and have been misfolded to form aggregates. This is important because Parkinson’s disease severity strongly correlates with the accumulation of these protein aggregates of alpha-synuclein within the neurons, creating big chunks of proteins called Lewy bodies, which cause the neurons to die.

Our process gives us a window into the brain, where the disease occurs, because the exosomes we are isolating come from there. We can monitor progression because as the disease becomes more severe, the number of these misfolded proteins will increase.

What real-world problem does this solve?

The brains of living patients are just not accessible – you cannot biopsy the brain, right? So, there’s no regular testing for Parkinson’s disease. People don’t come to the doctor to start the diagnostic process until they begin to show symptoms. Then, clinicians perform imaging, which can only detect issues late in the disease progression. The problem is that by the time Parkinson’s disease is diagnosed, most people have lost around 60%-80% of their dopamine-producing cells in the part of the brain that is essential to movement.

Once the cells die, you can’t get them back. However, before you show symptoms, cell death is very slow. It starts a decade before you see signs of the disease.

So, our diagnostic technology would allow people to undergo blood tests when they are maybe 40, 50, 60, and 70 years old. If we detect it early, it opens a much larger window for intervention before it’s too late.

What inspired you to get into this field?

I’m a biomedical engineer by training. My Ph.D. at Amit Meller’s lab was focused on fundamental research. I developed nanopore sensors, building the electro-optical setup and fabricating the nanopores. This technology was fascinating but very far from actual patients and clinical applications. In my postdoc, I wanted to work with clinicians, understand their problems, and develop tools to address their needs.

Tal Gilboa on Opening a Window into the Brain for Parkinson’s Diagnostics
Tal enjoys opportunities to mentor and teach others. Here, she presents her work to colleagues at the Wyss Retreat in 2022. Credit: Wyss Institute at Harvard University

Around when I started my undergraduate degree, my mentor, who I worked with on my bachelor’s thesis, was diagnosed with Parkinson’s disease. He was a professor in my department and, coincidently, a friend of my parents. Seeing the fast progression of the disease and how quickly it destroys a person’s life to the point where they cannot be independent anymore was pretty shocking. It’s striking and horrible. That’s why I came to David Walt’s lab – I knew they were working on Parkinson’s diagnostics.

What continues to motivate you?

The science, obviously, but the other thing I love about working in a university environment is the opportunity to teach and mentor. We are growing the next generation of researchers. That’s something I’ve always been passionate about.

What excites you about your work?

In the day-to-day it’s mostly the people because we have a great team. I’m fortunate to work with a diverse group of biologists, chemists, and engineers.

Here, we’re focusing on things that can help people right now, not fifty to a hundred years from now, and that’s thrilling.

Tal Gilboa

We also collaborate with clinicians to see the real-world problems we’re trying to solve up close. That’s very exciting because it’s so different from my Ph.D. It was so cool to develop electro-optical sensing in nanopores, but the focus was completely different. Here, we’re focusing on things that can help people right now, not fifty to a hundred years from now, and that’s thrilling.

What are some of the challenges that you face?

It’s very hard because we’re solving a huge, difficult problem. For this research to be successful, so many pieces must work. For example, we must be able to detect these brain markers in the blood. We have to quantify these very specific proteins. Every piece is challenging on its own. Now, put them together, and you have something incredibly complex.

You can’t control biology. Sometimes, you develop something that sounds amazing, but it’s just not working when you use clinical samples. This is why developing something that can have near-term impact is exponentially more difficult than just developing something that’s cool. Every aspect of the project is challenging technically and biologically. However, that potential for improving lives makes it worth it.

Why did you want to work at the Wyss?

I’m a biomedical engineer, so it was always about combining different fields resulting in interdisciplinary research. The Wyss is exactly the type of environment I was looking for – a place where great technologies are developed in collaboration with world-class hospitals. When I got here, I found that the freedom we’re afforded as postdocs is amazing, and the people who work here are great.

The Wyss is exactly the type of environment I was looking for – a place where great technologies are developed in collaboration with world-class hospitals.

Tal Gilboa

What is unique about the Wyss and how has that impacted your work?

As a member of the Walt Lab and the Wyss Institute, I have a lot of independence to be creative and explore new things, which is unique. That and all the open space fosters a research atmosphere where people collaborate.

It has impacted my work because I’ve been involved in so many collaborations since starting as a postdoc. I’ve collaborated with members of the Don Ingber, Dave Mooney, Natalie Artzi, Dave Weitz and George Church labs.

All of this was especially prevalent during the height of the COVID-19 pandemic. I was attracted to the Walt Lab because of the work on Parkinson’s disease, but about six months after I started, the pandemic hit Boston. We had the freedom to pivot toward COVID diagnostics. That accelerated our work in developing technologies that were immediately useful to patients and ramped up collaborations across the Institute.

I also appreciate the support from teams across disciplines at the Institute, from the bioanalytics team assisting us with our image processing to the sponsored research team led by Paula Cornelio and the rest of the administrative staff.

How have your previous work and personal experiences shaped your approach to your work today?

My Ph.D., which was super exciting and interesting, gave me a lot of technical skills and taught me how to plan experiments. It also gave me a lot of teaching experience. Then, ever since I was a child, I enjoyed working in teams. I’ve played team sports, especially soccer. I use practical research skills and teamwork every day.

When you’re not in the lab, how do you like to spend your time?

Tal Gilboa on Opening a Window into the Brain for Parkinson’s Diagnostics
Tal, her daughters, Ofri and Shay, and her husband, Dror, taking a break from hiking. Credit: Tal Gilboa

I have a family – my husband and two daughters – and I enjoy spending time with them. We love hiking, watching sports, camping, listening to music, and painting. Mostly, I just appreciate being a child again by playing with my daughters. I also like to read and spend time on the beach.

What’s something fun about you that someone wouldn’t know from your resume?

I spent a year backpacking through South America in my 20’s, and that I’m a die-hard fan of the Italian soccer team!

If you had to choose a different career path, what would it be?

The first thing that comes to mind is being a teacher. I think there are two actions we can take to affect society – one is doing what I’m doing now, which is research that relates to finding new treatments to medical problems. The other is educating the next generation and teaching children to be more tolerant and accepting. Helping to mold kids is another excellent way to make a positive change.

What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?

It’s just incredible! It’s nice to work on big problems that could really help so many people and improve their lives. It’s also amazing to be able to collaborate with so many individuals from so many different fields. I think we are very fortunate to be here and be able to do this, even for just a few years. It’s amazing.

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