An Interview with Sophia Liu, the Newest Member of the Ragon Faculty

Date: September 1, 2023 By:

With the launch of the Liu Lab today, the Ragon welcomes its newest Early Independence Fellow — Sophia Liu, PhD, and her team will spend the next five years building tools to study cell interactions in order to further our understanding of, and find ways to improve, the human immune system.

The Institute is honored to welcome Dr. Liu to our faculty, with her highly impressive career spanning Harvard, MIT, and even previous work at Ragon labs! We spoke to her about her background, what she hopes to achieve, and what this position means to her.

Could you tell us about your research background and what drew you to your field?

“It’s kind of funny; I’ve crossed paths with the Ragon many times over the last decade. When I started my undergrad at MIT in chemical engineering, I was excited to fix things. When I see something in the world that doesn’t align with how I think it should be, I get curious and gravitate toward fixing it. A natural setting to do this is immunology.

My first interaction with the Ragon was in 2013 working with Ragon alumnus Armon Sharei, who at the time was doing research that resulted in the creation of SQZ Biotech, a cell therapy biotech company. The goal was to engineer T cells, or adaptive immune cells more generally, to be able to target diseases in a directed way. I was excited about the potential of immunotherapy and felt very lucky to help with that project. 

Around 2015, Armon decided to focus on SQZ full time, and I transitioned to working in Alex Shalek’s lab at the Ragon. At that time, Alex was a relatively new faculty member and his work expanded how I thought about research. We connected over the same goal of trying to engineer cells to help people, but I learned there were big gaps in studying cells and developing tools to study cells. Alex’s lab highlighted to me that we need to understand the differences between cells to make therapies better. 

My graduate work at Harvard in biophysics started in 2017 in Fei Chen’s lab. I wanted to build tools to look more closely at cell interactions — how does one cell affect another cell? How does a tumor cell prevent an immune cell from doing its job? How can we better understand the problem to engineer things to fix them? I’ve built methods for studying immune cell interactions in tissues, and received support from an Impetus Grant to study how tissue-level changes during aging affect our immune systems. I’ve loved working on these exciting questions, and am thankful for all the inspiring mentors along the way.”

What kind of research will the new Liu lab be doing?

“My lab follows the same trajectory of building tools to understand the immune system, particularly human immunity. I’m interested in tools that study spatial cell-cell interactions and can make measurements on long timescales. Many tools that we use consider a short timescale, but there are problems that are related to aging — for example, increased disease burden and reduced vaccine response in older populations— that we need different tools for. 

There is a push and pull of technology development where the kinds of problems we can solve are enabled by the tools that we have. I’d like to build tools that open up the set of questions that we can ask. Focusing on being able to ask questions and building new tools to answer those questions— that cycle is something I hope my lab will contribute to.” 

Was there any specific event that sparked your interest in immunology research and bioengineering?

“I’m going way back to my childhood for this. I grew up in a relatively low-income household, so one of the best things as a kid is the library because there are so many free books. I fell in love with books and reading then, which led me to become an annoying, very curious kid filled with a lot of questions. I still remember one of the first books that my mom got me, which was something like, ’50 Experiments You Can Do at Home.’

The experiments were classic —  ‘build a volcano’ or ‘lava lamps.’ I never actually did them, partly because we didn’t have the money to buy all the materials and partly because my mom didn’t want me to make a mess. So I would sit there imagining what the experiments would be like, what they would look like if you changed some parameters. A lot of my time was spent observing the world and thinking in my head about the problems. 

I started looking at the people around me and seeing them get sick. That was one problem that stuck out to me. I started daydreaming about how we could change those things and it all developed from there. I think, perhaps, my mom knew that the real value of the book wasn’t following the instructions but rather being able to imagine the possibilities.

As an aside, there’s this cool study on women and men scientists. When asked how they got into science, women usually say, ‘I had a really good teacher.’ Men tend to say things like, ‘I was naturally curious.’ For me, it was both. I was naturally curious, but I also had very good teachers who were passionate about disease and biology.” 

What motivated you to apply for an Early Independence Fellowship?

“My PhD mentor, Fei Chen, was also a fellow at the Broad Institute. I was actually his first graduate student. When I started, we were buying equipment, setting up computational pipelines – we were doing all these things to build up a group, and I got a taste of what it was like to start a lab. 

That part of it, I think, is amazing, and I really recommend it to graduate students. Working with a young person starting a lab is one of the most rewarding experiences. You get a lot of exposure to building up a lab, and the whole process seems less daunting because you’ve been through it. You get to learn things and connect things in a way that when you’re in a really large, more established lab, you don’t get. There are other trade-offs, of course, but by the end of my PhD I had a solid vision of what I wanted to do, and I didn’t have this fear of the unknown. The combination of the two encouraged me to apply.”

What specifically appeals to you about the Ragon Institute?

“So many things. When I was applying, the Ragon was the dream position. It’s the community here. People here really like each other at every level and it’s nice to see that. There’s a mixing of mentees and mentors. People know each other’s family’s names, and that’s something that I’m hoping to be a part of and build up as well. The community is a big draw and the science speaks for itself. 

The focus on human immunology is important to me. A lot of immunology has been built off of really, really good mouse work. Many of my interests lie in trying to connect more with human biology. It’s exciting that the Ragon is an entity that has done and continues to do that.”

Is there anything you have found surprising or unexpected over the course of your career?

“So I was guilty of this – sometimes scientists, especially early in their careers, label certain areas of science as not being interesting. I think people do this as a way to establish what their interests are. Like, ‘Oh, I don’t find this other work interesting. That makes my work more interesting as a result.’ Over time, I’ve realized that everything is interesting — the more you try to find exciting aspects or try to understand why someone else finds an area of science attractive, the more you can discover important intersections between their work and your work. I find that creativity is just opening your mind to different directions and finding the overlaps. Creativity is a choice.”

Other Fun Facts

  • Liu once ran in a 200-mile relay.
  • If she could collaborate with any researcher, dead or alive, it would be Nobel Prize laureate Barbara McClintock.
  • Her nickname in Alex Shalek’s lab was “Fun Fact” because she always had a fun fact to share.

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