Undergrad seeks answers to a mystery of pancreatic cancer

Jesse Persily spent his summer chasing after answers to questions about one of the most deadly kinds of cancer.

Persily, a fourth-year human biology major, received a Harrison Undergraduate Research Award last year to perform research on a specific subset of cancer patients. His work analyzed cell surface receptors on pancreatic cancer cells in the context of liver metastasis.

“Even pancreatic cancer patients who are candidates for surgery typically die in the years following the removal of their tumor, commonly as a result of liver metastasis,” said Persily of Marlboro, New Jersey.

Persily, and the team in Dr. Todd Bauer’s laboratory, developed a way to model clinical relevant scenarios in mice. The process takes advantage of the intrinsic ability of cancer cells to divide repeatedly. When a tumor is removed from a patient, small tumor chunks are sewn onto the pancreata of mice. The resulting tumors can be minced into what are called “patient-derived cell lines,” which can be grown for months at a time on cell culture dishes, or frozen for later investigation.

“By injecting tumor cells into the spleens of mice, we are able to recapitulate the path an actual tumor cell might take through the blood stream to metastasize or spread from the pancreas to the liver,” Persily said. “We can then study the disease in the context of the liver micro-environment, or the subset of cells that typically exist and move in and out of the liver, to better understand the way tumors develop in this space.”

“We are actually hoping to learn how to eradicate the cells that get to the liver before they grow out or become a full tumor,” Persily said. “We have found, in both patients and in the model, that there is a ‘dormancy phase’ in between the tumor arriving at the metastatic site and actual tumor outgrowth, and so we think this is a period of vulnerability where we could eradicate the cells.”

He said they were not able to track the migrating cancer cells on their way to the liver, but they can track their growth rates once they arrive.

Persily found the cancer cells with which he was working did not react as he anticipated.

“We essentially expected a sorted subpopulation of cells to grow more aggressively, because other groups had shown that in other types of cancer and in other models, but when we did not see this, it forced us to think about what made our model different, and about exactly what question we were asking in order to explain the results,” Persily said.

Persily, who was drawn into cancer research by relatives who suffered from other cancer diagnoses, works in Bauer’s laboratory with lab technician Sara Adair and surgical residents.

“I was drawn to the Bauer lab because I was interested in pursuing a career in medicine, and the opportunity to work with a physician who also ran a basic science research lab seemed too good to pass up,” Persily said. “I thought it would allow me to look at academic medicine from a number of different perspectives.

“I was drawn to pancreatic cancer because I knew it was a disease with a horrific prognosis, worthy of active investigation,” Persily said. “Finally, I knew that surgical residents spent time in the lab, and I loved the idea of getting to work with physicians in training.”

Bauer, an associate professor of surgery, said Persily is bright, motivated and a joy to have around.

“His contributions on the project, along with the rest of the team, have helped identify a novel approach to adjuvant therapy for pancreatic cancer,” Bauer said.

As well as his contribution to cancer research, Persily’s time in the lab has taught him to more critically assess his own and others’ research.

“By developing an understanding of the underlying biology and common methodology, I’ve learned how to put new findings in the context of old information,” he said. “I’ve also learned that the experiment you design dictates the questions you can and can’t answer, which has allowed me to critically assess the conclusions that others and myself draw from the data.”

Through his research, Persily found that he is fascinated by the unknown.

“I’ve learned that I love the process of taking information, synthesizing it, and using that to come up with intelligent, answerable questions,” he said. “I’ve learned how to fail, and that in science, it’s not about the failures, but about how you move forward from them, how you shape your understanding of the biology based on the answers you get, so you can continue to work toward a goal, even in the face of data you didn’t expect.”

Source: University of Virginia