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Yuwen Zhu in the lab | University of Colorado Cancer Center

Unleashing Immune-Cell Soldiers: Yuwen Zhu, PhD, Journeyed from China to Colorado in His Quest to Fight Cancer

The CU Cancer Center member seeks new pathways for immunotherapy, and advises young researchers to have passion and curiosity.

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Written by Mark Harden on May 26, 2024
What You Need To Know

May is Asian American, Native Hawaiian, and Pacific Islander Heritage Month. This is one of a series of profiles of University of Colorado Cancer Center members from those communities who have overcome challenges to achieve success in cancer research.

Yuwen Zhu, PhD, grew up in a rural village in China. His mother couldn’t read. “I really didn’t know about college – even what the word meant,” he says.

Not the most likely start for a man who became a University of Colorado Cancer Center member known for many years of groundbreaking cancer immunotherapy research.

Zhu – an associate professor of surgical oncology in the CU Department of Surgery – set out on the path that led him to his cancer research career when he entered a good high school in another town, where many of the students were studying for college. “It was very competitive and you had to study hard,” he says. It was a boarding school, so there wasn’t much else to do but study.

He was accepted as an undergraduate at Nankai University in Tianjin, China, where he studied microbiology in the early 1990s. He later advanced to the Chinese Academy of Sciences in Beijing, where he earned his master’s degree in microbiology.

“In college I started to realize that a lot of people went to the United States for graduate studies,” Zhu says. “I was influenced by the people around me, so I started to prepare.”

No ceiling

Zhu recalls those years as “the most difficult time” in his academic journey. “It used to be that my study was all mentored by teachers. You just follow the assignment. But to prepare for these tests, I was by myself. And there was no ceiling – no top score that would guarantee that you would go somewhere. You just had to do your best.”

His best, it turns out, was good enough to get him into the Mayo Clinic College of Medicine in 2001 as a doctoral student. And he was ready for a shift in focus.

“I had studied microbiology, but I got a little bored with that. I wanted to work on humans. A medical school gave me the chance to study the patients’ diseases.”

Zhu credits his Mayo Clinic advisor, and later his collaborator, Lieping Chen, MD, PhD, with introducing him to then-novel ideas about using immunotherapy to unleash the power of patient’s immune systems against cancer.

Zhu pursued a PhD in immunology. At first, he focused on PD-L1, a protein that is highly expressed in many cancers and helps keep the body’s anti-cancer immune response under control. Next, he pivoted to investigating ways to keep proteins called immune checkpoints from hampering T cells as they attack a tumor.

He followed Chen to Johns Hopkins University as a post-doc fellow, and then on to Yale University School of Medicine as an associate research scientist.

→ ‘Trust In Yourself’: Mayumi Fujita, MD, PhD, Has Overcome Challenges in Her Cancer Research Career

IMG_7973_edited_editedYuwen Zhu, PhD, in the lab. Photo courtesy of Yuwen Zhu.

Expanding his horizons

Eventually, Richard Schulick, MD, MBA, whom Zhu had met at Johns Hopkins, recruited him in 2013 to the CU Department of Surgery, where Schulick had become chair the year before. A few years later, Schulick became the director of the CU Cancer Center and has been a frequent research collaborator with Zhu.

Meanwhile, Zhu was expanding his immunotherapy research horizon. In recent years he has been exploring ways to help immune cells or antitumor agents to get into the tumors. One of the approaches is to normalize tumor vasculature — a tumor’s network of blood vessels — in order to improve pathways to the tumor so drugs and the body’s immune killer cells can better reach and attack the disease. This type of therapy the Zhu lab discovered is now under a phase 1 clinical trial across many big hospitals in U.S. and Australia, including the CU Cancer Center.

“Tumors need nutrition to grow, so they produce a lot of blood vessels to get nutrition from,” Zhu explained in a 2021 interview. “But that vasculature is immature and irregular, kind of leaky, so basically the blood vessels are not very well-connected, not very functional in terms of the oxygen transport.

“Because they’re leaky and immature, they’re not good for immune cells to travel through to get to the tumor tissues. If we can convert the dysfunctional tumor vasculature to functional, mature vasculature, that helps drug delivery, that helps the immune response and mobilizes immune-cell soldiers to those tumor sites.”

Zhu has focused on pancreatic cancer, which he describes as “immunologically cold” – not responsive to current immunotherapies.

IMG_5066_editedYuwen Zhu, PhD (left) and his lab members enjoy a meal. Photo courtesy Yuwen Zhu.

Passion and curiosity

As a researcher in the fight against cancer, Zhu says he admires the CU Cancer Center and the CU Anschutz Medical Campus as being “more collaborative, not as competitive as on the East Coast. And as a scientist in the Department of Surgery, I can form partnerships with clinicians and surgeons. It’s very helpful for me to know what’s happening in the clinic.”

Zhu advises young people interested in research careers that “passion for the work is very important. This kind of job is not a way to become a millionaire. A lot of your life is concentrated on the research. Even on vacation, my brain is still in the lab. You have to be curious. And you have to deal with administrative things like writing grants. It’s not 100% lab research.”

Asked what adjustments he had to make coming from China to the U.S., Zhu has a quick answer:

“The food! Our family had to cook every meal. When we were looking at new cities, we always asked, are there good Asian markets? So when I interviewed in Colorado, we found there was a Korean market, H-Mart. They have vegetables that a supermarket doesn’t have. That was a huge deal for us.”

Photo at top: Yuwen Zhu, PhD, in the lab. Photo courtesy of Yuwen Zhu.

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