The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as professionals, and their collaborations at the Wyss Institute and beyond.
When Clarissa May Babila was in elementary school, there was one movie she wanted to watch over and over: a PBS documentary on Rosalind Franklin. That early love for science led her to an undergraduate research position, where she realized she enjoyed learning about how a disease worked, but also wanted to do something to help patients. Now, she’s part of the Wyss Diagnostics Accelerator, using extracellular vesicles to better understand diseases like Parkinson’s and Alzheimer’s, with the eventual goal of finding a way to diagnose them earlier. Learn more about Clarissa and her work in this month’s Humans of the Wyss.
What are you working on?
I’m part of the Wyss Diagnostics Accelerator (DxA), but my research falls mostly within the expertise of David Walt’s lab and my primary mentor, Dima Ter-Ovanesyan, is in both the Walt and Church labs. I’m primarily working with extracellular vesicles, or EVs, which are basically small packets of information that cells release, almost like sending a package in the mail. These “packages” can contain proteins, RNA, and DNA.
We’re trying to isolate cell-specific EVs and use them to get a better understanding of what’s happening in difficult-to-access organs. Specifically, we’re trying to understand what goes on in the brain of Parkinson’s and Alzheimer’s patients. So, we’ve been looking to isolate EVs that are specifically released from diseased neurons. That entails finding a protein that is uniquely expressed in neurons and present on the surface of EVs, so we could use that protein as a biomarker for EVs originating from neurons
What is the Wyss Diagnostics Accelerator?
The Wyss Diagnostics Accelerator collaborates with clinicians who have unmet diagnostic needs. This could be one that is not well studied or just does not have a good diagnostic test. Our work can fast-track the creation of new diagnostics, and we know it will have impact because we’re learning exactly what doctors need.
What real-world problem does your work solve?
This work is important for understanding disease progression. Right now, there’s no way to comprehend what’s happening biologically within these dementia patients without taking a brain biopsy, which just isn’t possible. Also, with Alzheimer’s, for example, you don’t know someone has it until they’re exhibiting symptoms, but at that point the disease has already significantly progressed.
So, if we can isolate these neuron-specific EVs, it would give us a window into the brain, and potentially allow us to create a better diagnostic or even lead to better therapeutic options if the disease is caught soon enough. An early diagnosis might also help patients and their families cope emotionally by giving them more time to prepare before the disease progresses.
What inspired you to get into this field?
When I was a kid, I was obsessed with learning about scientists like Marie Curie and Rosalind Franklin. Rosalind Franklin discovering the structure of DNA was just so exciting to me! I remember watching a PBS documentary about her in my fourth-grade science class, and I loved it so much that my dad bought me the DVD so I could keep rewatching.
When I got to college, I thought I was going to translate my love for science into a career in medicine, because my mom is a physician and that’s what I knew. Then I got the chance to participate in research, and I really enjoyed that because I felt like I was learning about the disease itself and how it worked, whereas a physician focuses on making a diagnosis and treating the disease.
What continues to motivate and excite you?
Here at the Wyss, there’s a big focus on translation. As we’re doing the research, we’re thinking about how we can scale it up to make it clinically relevant. For example, right now we isolate the EVs by hand, one sample at a time, but we also developed a protocol to do the process using a Tecan liquid handling robot, which would allow us to do 24 samples at once.
In research, it’s exciting to be curious about what you’re doing, but I’m motivated by taking it one step further to say, ‘Okay, we have this better understanding of the disease. How can we scale this up to make it something that anyone could use?’
What are some of the challenges that you face?
The main challenge is creating reproducible results. Sometimes, when we’re validating specific proteins as potential neuron EV markers, it might look great in one sample, but if the signal isn’t as strong in the next sample, then that protein isn’t the right one. It’s important because if you have a diagnostic that goes to the clinic, you want to ensure there are standards that are met every time you run the test.
Why did you want to work at the Wyss?
Originally when I graduated college, I wanted to focus on clinical impact. So, I thought I should work at a biotech company. Then I realized the type of work that I’d be doing there wouldn’t develop a research mindset. Instead, I’d be running a protocol that’s already been optimized and validated. I really wanted to get into the nitty-gritty of how to develop something from scratch, from idea to validation to commercialization. The Wyss was really attractive to me because it’s a blend of academia and industry. There are a lot of people here who spin out companies, and a lot of talks where we can learn about experience in industry.
How has this unique mix of academia and industry impacted your work?
It’s really helped me think about my research differently. In undergrad, it was mainly focused on satisfying curiosity about a certain aspect of a disease and publishing a paper. Here, there is emphasis on how to scale up our work and ensure it has impact.
How do you collaborate with other teams from across the Wyss Institute?
A nice thing about being in the DxA is that I can work across multiple labs. The main collaborations I have are with the Church and Walt labs. We’ve been focusing mainly on the proteins in the EVs. The Walt lab is an expert in using a technology called SIMOA, which is a highly sensitive digital ELISA that can detect and quantify proteins in a sample. We use that to create assays to help us determine if our protein of interest is on EVs and would be a suitable biomarker.
Now, we’re moving into characterizing nucleic acids in EVs, so DNA and RNA. The Church lab has a lot of expertise in nucleic acids. So, it’s great to have access to all this knowledge in one place.
How have your previous work and personal experiences shaped your approach to your work today?
During my undergraduate studies I did research studying pediatric high-grade glioma, which is a very aggressive form of brain cancer. We used nanopore sequencing to detect point mutations that are indicative of the cancer in cerebrospinal fluid (CSF) samples, because they have circulating tumor DNA in them. When I graduated and joined the Wyss, I learned about the potential to use EVs for diagnostics. I was attracted to that because I could use my experience and knowledge of diagnosing brain diseases to develop less invasive tests. EVs can be obtained from biofluids like blood, while CSF is typically obtained from a lumbar puncture.
That experience also shaped how I approach my work now, with an emphasis on translation. In undergrad, we did this study where we were able to track the progression of a tumor in response to a certain treatment, and the tumor shrunk. Also, the variant allele frequency of the point mutation had decreased. It was great because we had support at a molecular level and from imaging that the tumor was responding to the treatment! But we just did that one study, published a paper, and then at the end said, ‘Oh, this could be a great clinical application.’ And that was it. I realized I wanted to focus on clinical application, and in traditional academia, that isn’t always the case. Here it’s really at the forefront.
When you’re not in the lab, how do you like to spend your time?
I really like to go on walks around the city, exploring local bookstores and coffee shops. Because I do spend a lot of time in lab, it’s nice to get outside. I also really enjoy reading, mainly science fiction. I’ve also gotten into going to concerts!
What’s something fun about you that someone wouldn’t know from your resume?
I really like hiking. Unfortunately, I don’t have a car here so it’s hard to do now. A few years ago, I went on a road trip with my friend from college. We took two weeks and drove from Seattle to Michigan, where I’m from. On the way, we hit a bunch of National Parks, like Banff, Yellowstone, and Glacier. Glacier was my favorite, because while the other parks were beautiful, they were much busier. I enjoy being immersed in nature. I’ve been to many more national parks since then and I’d eventually like to visit all of them!
If you had to choose an entirely different career path, what would it be?
I think I would have been a writer. Besides science, I really loved reading when I was a kid. I took a creative writing class in high school. In another life, maybe that’s what I would have done.
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?
I think it’s really exciting. My undergraduate research was at University of Michigan, which is a big research university with tons of resources, but for the high-throughput work we’re doing, the Wyss has even more. Any equipment I need is at my fingertips. It’s amazing that there aren’t any barriers stopping me from doing this impactful work.