Tag: Zhang

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.

For more information, email comm-marketing@wistar.org.

Few biologists can say they saw a type of cells for the first time. Nan Zhang, Ph.D., who started at The Wistar Institute in September as an assistant professor, became one of those biologists when, during his postdoctoral research at Washington University in St. Louis, he peered through a microscope into the abdomen of mice and spotted macrophages floating in the cavity. Before that moment, these immune cells had been seen in other compartments in the body, but they were always anchored to tissues.

Nan fondly remembers the day of that discovery, five years ago, and prizes the first video he took of the floating macrophages. “I’m putting this video on my website and trying to put it everywhere. I’m so proud of this, it is really the first of the first,” he said. Along with getting very cool images, Nan’s work shed new light on important functions of these so-called resident peritoneal macrophages. At Wistar, he will use this insight to explore how these cells influence the outcomes of a major disease of the peritoneum, or abdominal cavity: ovarian cancer.

First and Last

It almost felt like a sign that Nan’s first job interview was at Wistar, the place he had his heart set on working. The Institute’s triple focus on cancer, immunology and virology aligned perfectly with Nan’s interests. Of course those kind of stakes only made the interview more stressful, but Nan laid it all on the line. He was shocked when he got an offer, and accepted it without waiting to look at any others.

Nan has trouble naming just one reason — or even three — that he is thrilled to be joining Wistar. He is excited that the small private institution will afford him the time to focus on his own research, without classes to teach, at least for the first several years. At the same time, he can get the feel of a larger research community when he wants it by attending seminars and conferences across the street at the University of Pennsylvania. Last but not least, Nan looks forward to the outstanding facilities at the ready for Wistar scientists, including the special two-photon microscope that will be key for his upcoming studies of peritoneal macrophages in living mice.

Chasing Mysteries

Growing up in China, there were two main influences that fostered in Nan a general interest in science: conversations with his dad, who is a professor of urban design, and children’s magazines about space science and other areas of science. Astronomy was actually Nan’s first real love in science, and he continues to watch videos and listen to podcasts about the topic. He also enjoyed courses in physics and chemistry, and the calculations behind them — basically anything but biology, which in his high school amounted to just a bunch of memorizations.

One day, when Nan was about 16 years old, while waiting on their bikes at a red light, Nan and a friend embarked on a “what if” conversation that awakened in him a fascination with biology and set him on a new path. The pair mused about whether human beings could become immortal by transplanting the memories of one person into a younger person’s body — a science fiction fantasy that Nan noted some people claim they can achieve. It left Nan inspired to ponder ways to improve human health and longevity. When it came time to declare his university major, which in China generally happens at the time of entry, Nan was split between biology and astronomy, but his parents urged him to think about career prospects. He picked biology, reasoning that there will always be jobs for people who study health and disease.

During his Ph.D. research at the University of Oklahoma Health Sciences Center, Nan was struck by another biological mystery, this one more solvable than immortalizing people. As inflammatory cells called neutrophils flood the peritoneal cavity in response to an insult, macrophages — which are immune cells that engulf and destroy invaders — disappeared from the cavity. Nan was so intrigued that he considered switching Ph.D. projects to study this strange phenomenon, which had first been documented decades before, but his advisor cautioned him to stay the course. Instead, Nan read all he could about macrophages in the peritoneum as well as subsets that reside in other tissues and organs, and their different gene expression profiles and characteristics.

By the time he was looking for postdoc positions, Nan had no doubt that he wanted to investigate what peritoneal macrophages were doing and whether they truly had different functions than other subsets of macrophages. What he discovered actually helped solve the puzzle of the macrophage disappearing act. When he injected agents that mimic infection in mice peritoneum, he realized the macrophages clump together, entrapping microbes and clearing them away. Now Nan plans to ask whether the same processes may allow these macrophages to aggregate around ovarian cancer cells, possibly either preventing or promoting metastasis. He will also explore the role of other macrophage subsets in the peritoneum in ovarian cancer progression.

Looking Outward

Nan cannot get his research program at Wistar up and running fast enough. For that reason he is pleased that his lab space is right next to the building entrance, no need to climb stairs or wait for elevators. “If I could teleport to work, I would probably just teleport,” Nan joked.

Near the top of Nan’s to-do list during his first weeks at Wistar is to apply for another big federal grant to fund his research. It will require a lot of writing, which Nan despised during school and his scientific training. It was actually the major reason he doubted his dream of becoming a professor. But the perfect score and enthusiastic feedback he got for his previous grant, which is supporting his transition to an independent scientist, infused him with the confidence that maybe he could make it in academic research.

In the second half of Nan’s postdoc, he made another realization that bodes well for the path ahead: He really enjoys mentoring young scientists and watching them grow. He knows he will be giving them a lot of guidance and cheering along, like his advisors gave him during rough times when experiments did not work. He also looks forward to unleashing the members of his lab to be creative and think crazy thoughts, just as his postdoc mentor encouraged him to do.

As Nan and his wife settle into their new home, he looks forward to nurturing in his five-year-old son the love of science his own father shared with him. Their early discussions together will probably center around Nan’s other science fascination, astronomy. As soon as he can, Nan is going to buy his son, and himself, the telescope he has always wanted.

Written by Carina Storrs, Ph.D.