Dr. Jung Wook Park

PREVENTING ONE CANCER FROM BECOMING ANOTHER

by WHITNEY J. PALMER

For JUNG WOOK PARK, PHD, the spark to study and better understand how cancer works came early when, as a middle schooler, he questioned his grandmother’s oncologist about whether replacing her pancreas could cure her cancer.

“At that time, my definition of cancer was just a big ball that had grown in her body,” said Park, assistant professor of pathology. “I asked why he couldn’t just give her a new pancreas to fix it. He said it was impossible and that the cancer had already spread.” As Park grappled with the puzzle of his grandmother’s disease, he was also introduced to DNA manipulation via Jurassic Park. Dinosaurs aren’t related to cancer, he said, but seeing characters work with genes to revive prehistoric lizards put his mind to work.

“That’s how I got started with cancer research. I wanted to see how I could change the genes, alter the DNA,” he said. “How could I fix it? Could I make it normal?”

And with those queries, his journey to investigate how cancer cells develop—and to determine whether it is possible to detect malignancies earlier—was set. Today, he leads a lab in Duke’s Department of Pathology and focuses on the progression, changes, and treatment resistance of prostate cancer. But, to fully understand what’s going on, he studies the healthy tissue surrounding the cancer cells as well. “Most men with prostate cancer have adenocarcinoma, but in 20 to 30 percent of those cases, the cancer cells will change to block or avoid treatment— they will become small cell cancer,” he said. “But why? By looking at the benign, normal adjacent tissue, and changing the gene in the normal cell, I can see how that cell becomes cancer.”

Dr. Jung Wook Park

The Path to Pathology

The road to studying prostate cancer cells, however, wasn’t direct. While he applied himself academically in middle and high school in South Korea, by the time he reached college, Park was mentally exhausted—and his GPA reflected it. After his sophomore year, he took a step back to complete his three years of mandatory military service. Upon his return to school, he followed a friend’s suggestion and pursued working in a lab for the remainder of his undergraduate and master’s degrees. It was a far more attractive opportunity than sitting in the classroom, Park said. “It was very fun to do the research and not have to study the same way. Papers were being published every week or month, so there was always new knowledge coming. Reading about how people figured things out was strong motivation.”

Imaged under the inverted microscope, genetically engineered human cells are growing in an organoid. The red color indicates that cells were infected by viruses expressing cancer-driving genes.

Dr. Park explains: “Normal human cells are transforming into cancer cells in a dish. Normal human cells grow with viruses delivering cancer-driving genes in a three-dimensional culture system called an organoid culture. Each alphabet letter—C, A, P, or H—is indicating specific cancer-driving genes. Also denoting different human cell types are + and - symbols. Cells in yellow color wells are growing faster than in pink. These cells will be implanted into immune-deficient mice to functionally demonstrate their status of malignancy.”

When the time came for doctoral work, Park opted for a drastic change of venue, choosing to apply to numerous PhD programs in the United States. From his many offers, he selected the University of Wisconsin-Madison to study human papillomavirus (HPV). For this research, he used a mouse model to study how the virus—not genetics—led to cancer. With his post-doctoral work at the University of California-Los Angeles, though, Park pivoted to working with human tissue samples, investigating how cancer cells mutate from normal cells to cause disease. It was this move that led him to the work he does today, considering and comparing the healthy cells that surround malignant ones. To better illuminate how cancer cells work, he uses a novel ex vivo 3D organoid culture system that both identifies the origin cells for the disease and defines the genetic drivers behind the development and differentiation. “Being part of the Duke Pathology Department is great because I can get samples of both diseased and healthy tissue from the doctors who are mainly focused on a patient’s disease,” he said. “With those samples, I can add the cancer-driving gene into the normal cell and watch how it changes into a cancer cell while in a Petri dish.”

Working at Duke

Eventually, his work shifted from HPV to prostate cancer, and, as a result of his accomplishments, Park was named as the first recipient of Duke’s new professorship in pathology—the Rollie Endowed Assistant Professor for Correlative Pathology. It quickly became clear that Duke was a natural fit for Park’s research home.

Dr. Park with his lab team, (L-R) Yunsol Jo, Jongchan Hwang, and Chanjin Yoon

Not only does the University have a reputation for both national and international excellence, but the Medical Center also serves patients from Durham, aracial and ethnic melting pot. That diversity is critical because African American and Hispanic men have a higher prevalence of prostate cancer than white men.

“Duke has a good mix of African American, Hispanic, and white patients,” he said, “so, as a scientist, I have good access to patient tissue samples that can support my research.” But, when it comes to unearthing what makes cancer work the way it does, the partnership and collaborative opportunities Duke presents are equally—if not more—valuable than the chance to evaluate tissue samples. At every turn, Park said, he sees an avenue to work with colleagues. “Here, I can find easy collaboration not just with cancer biology, but with other scientists, as well,” he said. “For example, the chair of my department is a world expert in small cell prostate cancer. So, if I have a question, I can easily come to him and ask.” Ultimately, Park said, he sees his role and his research as being part of a much larger cancer effort. The fight to conquer cancer has been decades long, and the road ahead is still fraught with obstacles. But, if he can be integral in helping uncover how cancer develops for earlier identification, he said, it will be a goal fulfilled.

“I want to find out how we can detect cancer at the earliest time. If we can find the cancer as early as possible, then the patient has more of a chance to be cancer free,” he said. “There are a lot of smart people out there who are going to fix cancer, but I want to detect it early and block the transformation of cells, preventing one type of cancer from becoming another.”