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“Immunology is a Battlefield”: Wistar’s Dr. Nan Zhang on Creativity and Curiosity in Science

April 29, 2024

Dr. Nan Zhang, Ph.D., is an Assistant Professor in the Immunology, Microenvironment and Metastasis Program at the Ellen and Ronald Caplan Cancer Center. He studies the role of immune cells called macrophages in tumor growth and metastasis in the abdominal cavity and the ovaries.

Why did you choose to become a scientist?

My dad played a big role in my development. He was an urban planning professor , which planted the seed early on that becoming a professor would be great. We lived in China, but he came to the States when I was born and worked in upstate New York for a year and a half. It was an eye-opening experience for him. He brought back the ideas of experimenting and doing science, and those seeds just grew naturally in me.

In middle school and high school, I was good at STEM subjects, and when I applied to college, I chose to focus on biological sciences. As a sophomore, we could choose a sub-major within biological sciences, and there was a program in immunology that fascinated me, so I picked it. However, by the end of college, I was tired of rote memorization without understanding why I was memorizing it. You can know how to do things, which is the focus of a lot of schools in East Asia, but I think the more important question is: Why do you do it? This is why I chose to come to the States to enroll in a Ph.D. program. I wanted to learn how to think like a scientist.

How would you explain your research in immunology to somebody who is not a scientist?

Immunology is how your body reacts to foreign invaders. Your immune system is always fighting against unwanted intruders—pathogens, viruses, cancer cells—so I use the metaphor of a battlefield.

On a battlefield, there are soldiers who specialize in one type of strategy or terrain. These make up our adaptive immunity: T cells, basically the core cell type for current, groundbreaking immunotherapies. These cells are specific to a certain situation, like a particular virus or tumor cell, and they’re really good at fighting it.

What my lab studies are the types of soldiers who are equipped with general knowledge of fighting, which is called innate immunity. They’re not especially good at one type of fighting, but they might be good at learning and picking up new skills along the way. And as they learn, they will differentiate or develop into a more specialized type of cell.

I study macrophages, who are always on the battlefield. They stay there, respond when there’s an invasion, and then pass relay signals calling for help. When they’re calling for help, there are cells called monocytes, which are generalized but eventually differentiate into different types of macrophages, or soldiers. Then those cells send signals to the specialized soldiers, the adaptive immune system, who are better at killing pathogens.

My lab studies these innate immune cells because there’s a big gap in understanding what they are doing. They can develop into different types of cells, but how they develop, how they decide what cells they become, is not really known. Yet they are really important. These macrophages organize the battlefield, so to speak, so the adaptive immune soldiers know how to fight and what to fight.

It sounds like you have a lot of practice talking to laypeople about your work. Do you find that these conversations inform what you’re studying and how you talk about it?

Well, my son is one of the people who listens to me talk about my science. He will ask, “Why do you do this? Why is it important?” So I have to think of how I explain to an eight-year-old that what I do is important.

The most useful thing I’ve learned in talking to laypeople is that I need to understand and relate what I’m doing to the important medical issues they have. Laypeople don’t care about the detailed messages soldiers are sending to each other; they care about curing a disease and why the disease is killing people. And sometimes, when you’re writing grant proposals, it’s important to look back and see: Why are we doing this? Why should they give money to study this? I think that’s what talking to non-scientists has helped me do.

What do you think is the relationship between creativity and science?

Trying to be unique and different is what drives me to be creative, and being creative is how you find solutions in science. Connecting subfields is one way of standing out. Some of the most prominent scientists in my field are using ecological methods or equations to study how immune cells behave as a group, as a population. That kind of research is fascinating to me. It’s why I could never give up my deep interest in basic research and why I always have at least one basic research project in my lab.

Looking for new ways to do things and being creative also got reinforced when I was a postdoctoral fellow. My postdoctoral mentor is very creative. She connects dots like nobody I’ve met, and she made me recognize that there’s always an alternative hypothesis. You don’t have to be frustrated by a negative result. Just stay curious. It’s how we got to the moon and found so many cures: because we were curious for such a long time.

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