The Ragon is pleased to welcome Caroline Sokol, MD, PhD, as our newest faculty member. She leads the Sokol Lab as a Member of the Ragon Institute, while also serving as an Assistant Physician at Massachusetts General Hospital and an Assistant Professor of Medicine at Harvard Medical School.

A physician-scientist specializing in allergy and immunology, Sokol studies how the immune system recognizes and responds to allergens, with a particular focus on the neuroimmune circuits that underlie allergic disease. She received her BA and MS from the University of Pennsylvania, completed her MD/PhD at Yale University under Ruslan Medzhitov, PhD, and did her clinical training in Internal Medicine and Allergy & Immunology at Mass General. She previously led her lab at Mass General in the Charlestown Navy Yard before bringing her research program to the Ragon.

We spoke to Dr. Sokol about what drew her to allergy and immunology, the unexpected moment that pivoted her research toward neuroscience, and what she hopes to accomplish in her new role—

Could you tell us a little bit about your background and what drew you to allergy and immunology?

“I have always been interested in the immune system and how it can impact the body, cause disease, and heal disease. That puzzle has always fascinated me. Originally, I was very interested in a specific question: how does the immune system actually detect things—pathogens or anything that could hurt us or infect us?

When I started my graduate career in Ruslan Medzhitov’s lab, he felt that a lot of that question was already answered—we knew quite a bit about how pathogen detection happened. Instead, he thought one of the more interesting open questions was how we detect allergens. That’s actually such an amazing question. We know a lot about bacteria and viruses and how different they are from us: they’re prokaryotes, not big multicellular organisms. But when you think about the things that start type 2 immune responses, you’re thinking about things like helminth worms, which are multicellular eukaryotes like us, or really simple things like the foods we eat or pollens in the environment. It’s been such a big puzzle to understand how the body recognizes all of those disparate things, decides to start one immune response against them, and recognizes them as something different from ourselves. That fundamental question is where my entire career and interest in allergy has stemmed from.

There’s also been a real change in how we think about the allergic immune response—from one that is completely accidental and mistargeted against pollens, when it should have been targeted against tapeworms and things like that. That’s how we used to think of it. Now there’s a huge rethinking of it as an anti-toxin response, which makes a ton of sense, because the one thing all allergens share in common is toxic activity. When you view the allergic immune response as an anti-toxin response, a lot of things make sense—both in terms of what activates it and why it works so quickly. If you’re allergic to cats, the response is almost instant, and that immediacy is what really helps the body defend against toxins. Beyond that, it’s fun to study something that you see and experience in your day-to-day life. About 30% of us have some form of allergy, so getting to ask these fundamental questions about a type of immune response that so many people experience disease from is very rewarding.”

What was your path to coming to the Ragon Institute?

“My path to science and immunology started when I was in high school. A really fantastic biology teacher took an interest in me and wanted to show me what real science was like, so she found a way to get me into a lab at the University of Pennsylvania. That started this entire career, this entire passion of mine for immunology.

From there I went to Yale, where I did my MD/PhD. It’s funny, even though I did my PhD in allergy, I never expected my clinical career would be as an allergist. But sometimes it takes a while to find what’s obvious to everybody else. I came up to Boston to Mass General, where I did my residency in Internal Medicine and my fellowship in Allergy and Immunology. I also did postdoctoral work at MGH in Dr. Andrew Luster’s group, where we were trying to understand the movement of different immune cells in the allergic response. After that I started my lab at MGH in the Charlestown Navy Yard, where we switched focus completely and started looking at neuroimmune communication in allergy.

I had a fantastic start to my career there. But as I tell people, you get certain chances where you can move and really re-energize and restart your science in fundamentally different ways. I had collaborators at the Ragon (Alison Ringel has been a really helpful collaborator, and Bryan Bryson and I kept talking about ways to work together) and every time I met with them, I was so energized by the environment and by the breadth of science happening here. So when the opportunity came to move my lab over, it was a no-brainer. It was a chance to be in the place where I felt inspired, where I felt energized, where I was learning something new every day, and where I knew my trainees would be feeling the same way.”

Your research sits at the intersection of immunology and neuroscience. How does this neuroimmune approach differ from traditional immunology?

“We always think of the immune system as completely capable of sensing, responding, and bringing a tissue back to homeostasis on its own. But what we’re realizing is that there are a lot more interactions happening than we expected. Work by other groups has shown that the immune system and the nervous system can interact to promote inflammation and drive chronic inflammatory responses in tissues—and also to settle them back down.

Our path to neuroimmunology was completely accidental. I was really interested in how allergens are detected by the immune system—that was always the fundamental question I was trying to answer. We would get close; we found amazing stuff in the pathways downstream of allergen exposure, but we couldn’t figure out how the immune system itself was detecting allergens.

Then a funny thing happened. I was taking my three-year-old to taekwondo and he was running his hand along the wooden railing of our deck and hit a bumblebee. He got stung, and it was his first bee sting. That triggered something in me, because as an allergist I know that bee stings are the most robust, strongest allergen we’re naturally exposed to. It was an aha moment, because he was experiencing his first big allergen exposure, and his first response was not ‘Oh my goodness, I’m activating my type 2 immune response.’ It was ‘Ouch, that hurts.’ That told me his sensory nervous system was responding.

I had been a really strict immunologist until that moment, but I thought to myself, maybe I’ve been looking at the wrong cells this entire time. So I switched to looking at neurons. Very quickly, because we had the tools and collaborators in place, we were able to show that sensory neurons do respond to even less robust allergens such as house dust mite and things we use in the lab, and that that detection was linked to immune activation. We’ve been studying that connection ever since.”

What do you foresee as the most exciting aspects of your work over the next five years, both in the lab and in terms of potential impact for patients?

“We’ve been focusing on not only how neurons and immune cells interact to promote inflammation in allergy, but actually in all kinds of inflammatory diseases. We’re also looking at how environmental exposures change the neurons themselves and lead to feed-forward loops, where each exposure leads to more and more inflammation, which is obviously a setup for chronic inflammatory disease. 

By connecting immunology, neurobiology, molecular biology, human genetics, and model systems, we have some really exciting insights. We’re now at the point where we can draw out, and also take apart, some of these pathways within neurons and between neurons and immune cells. I think we can actually re-understand, or recontextualize, inflammatory disease not as a disease of the immune system, which has only gotten us so far with all the therapeutics we’ve made for patients, but really fundamentally as a neuroimmune disease.

What’s also exciting about being at the Ragon is working with people who think in different ways about different things. Every time I go to a talk by one of the Ragon faculty members, I think, ‘Oh wait, I’m thinking about this in a different way—that could be a really cool avenue to do something together.'”