Yunhao Zhai on Modeling and Understanding the Immune System

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 Yunhao Zhai was in school, he learned that the 21^st century would be the century of biology – and for his journey, that’s certainly right. He joined the Wyss four years ago, after studying biochemistry, molecular biology, and immunology in China and France, with the aim of addressing an unmet need for human in vitro models of the immune system. Now, he’s using these models to screen potential therapeutics and eventually increase the success rate of clinical trials. Learn more about Yunhao and his work in this month’s Humans of the Wyss.

What are you working on?

I’m working on the human Lymph Node Organ Chip platform, an in vitro model that mimics the human immune system. We can use this model to screen drugs and get fundamental insights into the human immune response to these therapeutics.

What real-world problem does this solve?

Most diseases are related to the immune system, but there are no good models to mimic the human lymph node function or other components of the human immune system in vitro. Animal models are not a good solution because their immune systems are very different from ours. There have been many cases where drugs work in animals and even in non-human primates, but they are not effective or even cause death during clinical trials. We want to reduce that risk. Organ Chips use human cells, so they can more accurately predict our immune response.

We are using these models to screen vaccines developed by industry partners, and also generate new therapeutics using the immune cells in these models. Understanding how a drug impacts the immune system and what dose is most effective can help ensure that more clinical trials are successful. Eventually, that will lead to better therapeutics for a wide variety of diseases.

What inspired you to get into this field?

I developed an early interest in science, and in China, you need to choose your path during high school. People used to say that the 21^st century will be the century of biology, so when I got to university, I chose to study bioengineering. I did my master’s in Shanghai and studied biochemistry.

For my Ph.D. I wanted to explore more translational science, so I decided to move to immunology because there are so many unsolved problems in this field. Scientists have so many great tools, like flow cytometry, single-cell sequencing, and multiplex imaging, and there’s always an application in immunology. When I saw the work coming out of the lab of my supervisor, Donald Ingber, I realized that they were trying to address an unmet need for human in vitro models, and I wanted to contribute.

What continues to motivate you?

It’s really the unmet needs – even if we find solutions for infectious diseases, there are other conditions like chronic inflammation and cancer that we still don’t really understand. Building these in vitro models will give us new insights into human immunology.

What excites you most about your work?

Making discoveries and working with great colleagues. Science is always a team effort. When I listen to a new seminar or learn a new technique, I feel like I’m standing on the shoulders of giants and taking one step forward. I enjoy pushing boundaries and forging ahead with my projects.

What are some of the challenges that you face?

Time is limited. I always want to explore more, but I need to focus on the tasks at hand. It’s also important to find good collaborators and mentors to get all of the knowledge I need. Sometimes, it feels like there is a never-ending amount to learn, but you must find the boundary of what’s important to move to the next step and do great science.

What is unique about the Wyss?

Compared to traditional academic labs, the Wyss is a very collaborative place. There are so many energetic and talented researchers who really inspire me. It’s easy to find potential collaborators, even during random chats over coffee. This isn’t a place where everyone just sits in their own corner of the lab – people want to work together.

Compared to traditional academic labs, the Wyss is a very collaborative place. There are so many energetic and talented researchers who really inspire me.

We also have support from other teams, like communications, business development, and patent lawyers. Their involvement shows us how to take basic research and translate it into a product that could really help people.

There are a lot of talented PIs that serve as great scientific mentors and motivate me to do my best work.

How has the environment at the Wyss impacted your work?

Having great mentors like Don and Girija Goyal is so important. Girija teaches me how the Wyss ecosystem works. For example, she helped me understand the technology development pipeline, and I was able to get Director’s Fund support to advance my project to the point where I could apply for Validation Project funding.

I currently collaborate with members in Peng Yin’s and David Walt’s labs. We all have different backgrounds and approach problems more comprehensively. Their labs have great diagnostic tools, and my understanding of immunology means I know unmet needs where we can apply their technologies. This organic merging of multidisciplinary researchers is only possible because of the environment at the Wyss.

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

I followed a very traditional path with my studies. I didn’t take a gap year. Because I skipped two years during my schooling, I’ve always been the youngest in my class. Knowing I’m ahead of the curve in some ways has given me the freedom to really explore and think about how to answer big questions.

At each step in my scientific journey, I learn new things, and I’m not afraid of that because each step you push forward gives you a chance to explore a new frontier.

I’m from a small town in China, so I had to leave my comfort zone to continue my studies. At each step in my scientific journey, I learn new things, and I’m not afraid of that because each step you push forward gives you a chance to explore a new frontier. That’s exciting to me!

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

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I enjoy traveling with my family. When I was doing my Ph.D. in France, we visited more than 10 countries together. If I had to pick a favorite place, it would be Florence because it’s small but full of history. There’s so much to see!

I also like to read – last year I read 200 books. My favorite genres are biography and history.

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

I like memorizing and reciting traditional Chinese poems. I have more than one hundred memorized. Reading these classical Chinese poems, many of which were written more than 1,000 years ago, relaxes me.

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

To combine my hobbies of reading and scientific discoveries, maybe I would be a traditional Chinese medicine doctor. You need to read a lot of literature, and there’s still science involved. You communicate with each patient to provide personalized prescriptions. It involves interacting with people and solving real problems.

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 a privilege. For biology, you need the support of your colleagues and a great infrastructure. I get to work with incredibly talented colleagues to solve real-world problems that impact so many people – from cancer, which impacts millions of people each year, to rare diseases, which have a huge impact on thousands of people. I truly appreciate this opportunity to make a difference.