Studying Immunology and Cancer, Nan Zhang, Ph.D., Delves Into Mysteries Of Ovarian Cancer Metastasis

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.