A Cold Place for Cures
The industrial-size freezer in Ellen Beswick’s laboratory – labeled “human tissue” and kept chilled to minus 150 degrees centigrade – might hold the key to cures for colon and gastric cancers.
With the help of her friend and colleague Dr. Katherine Morris, a surgical oncologist, Beswick has spent several years studying tumor samples in an effort to determine whether a malfunctioning immune response can trigger cancer.
Recently, that work has started to pay off. Beswick’s lab has identified an inflammation-promoting cell signaling pathway in mice that, when inactivated, stops these tumors from developing.
That pathway is shared with humans, says Beswick, who can’t disclose any other details because she has not yet published her findings. The discovery opens the door to testing drug therapies that could prevent these cancers from developing in susceptible individuals.
“Taking that information and developing it into a therapy for humans – that would be the next step,” says Beswick, an assistant professor in Molecular Genetics and Microbiology in the University of New Mexico School of Medicine.
The findings validate the team-based approach to translational research promoted at UNM’s Clinical Translational Science Center, says Beswick, who was originally hired as a CTSC scholar.
She and Morris are collaborating with Dr. Joshua Hanson and Dr. Von Samedi in the Department of Pathology, who have expertise in gastrointestinal cancers. “When we're doing our work, we need a pathologist to help us look at it and make sure we're seeing what we think we're seeing,” Beswick explains.
Morris, she says, “had some ideas on colon cancer and a certain aspect of the immune response that has not been well-examined,” Beswick says. Hanson “had a similar idea that melded with our idea.” He’s found a way to identify particular immune cells extracted from tumor tissues that seem to play an important role in promoting disease, she says.
It was the untimely destruction of a tumor tissue collection that prompted Beswick to bring her research to the University of New Mexico in the first place. She was running a small lab at the University of Texas Medical Branch in Galveston when Hurricane Ike swept ashore in 2008.
The storm, the costliest hurricane in Texas history, killed at least 195 people and knocked out power to Beswick’s lab – and then the backup generators failed. She lost painstakingly collected samples, and while colleagues were able to replace some of the collection, the disaster got her thinking about relocating to a higher and drier environment.
“Part of me wondered whether I should pursue some new opportunities if they came up,” Beswick says. When she found an ad for a job in a new translational medicine program at UNM, “it was very intriguing,” she says.
When she arrived in New Mexico in 2009, Beswick had already earned an outsized reputation for her work with Heliobactor pylori, a bacterium that in the 1980s was shown to cause stomach ulcers. Beswick’s research supported theories that long-term inflammation caused by chronic H. pylori infection was a risk factor for gastric cancer.
Many people around the world test positive for H. pylori infection, Beswick says, but only about 1 percent are diagnosed with gastric cancer (although it is the second-leading cause of cancer death worldwide).
As to why that may be, Beswick says, “I think it’s the combination of H. pylori and a carcinogen or an environmental toxin.” In fact, she says, she uses the bacterium and a known carcinogen to induce gastric cancer in mice for her research.
While Beswick has been looking at one cell-signaling pathway, Morris has been exploring another cell signaling protein called “granulocyte colony-stimulator factor” (G-CSF), which may play a role in stimulating tumor growth. Morris realized that when G-CSF was given to cancer patients who had low white blood cell counts due to chemotherapy, there was a trend toward decreased survival.
The substance raises levels of white blood cells known as neutrophils, Morris says. “There’s some indication they can be hijacked by the tumor to make the cancer more progressive,” she says. The neutrophils likely help the tumor bypass tissue barriers and escape into the body’s general circulation, promoting distant metastases.
Beswick and Morris first met in 2006, when Morris was practicing in Portland, Ore., and Beswick interviewed for a research job there. They reconnected in 2010 when Morris relocated to UNM. Now, Morris spends two days a week in their lab in the Multidisciplinary Research Facility, which is equipped with a flow cytometry machine (“a laser-based cell analyzer,” Beswick explains), and a device that performs real-time DNA analysis using the polymerase chain reaction.
Then there is the freezer and a backup collection of casks loaded with liquid nitrogen that can store tissue samples for weeks at a time.
“My whole goal in coming here was to be able to set up a translational research effort with someone,” Morris says. “It has been a phenomenally productive collaboration.”
Morris and Beswick spend a lot of time in the lab discussing research questions and working on manuscripts. Morris also alerts Beswick when she is scheduled to remove a tumor that a patient has consented to be used in research.
The samples come through the Human Tissue Repository, operated by the Department of Pathology. Normally, once they have used a tumor sample for diagnosis, pathologists discard the remainder, Beswick says. “Kate will let them know ahead of time and say, 'Please give this one to the Beswick lab.'"
The tumor samples can be analyzed in a dozen different ways, Beswick says. She can, for example grow connective tissue cells called fibroblasts from the sample, perform PCR analysis or study it for specific types of immune cells, like T cells and neutrophils.
“We’re analyzing things by tumor type and lymph node and metastatic stage,” Beswick says. “One of our big questions is what makes a tumor want to metastasize, because it’s the metastasis that kills the patient.”
Beswick, who with her husband spends a lot of her free time hiking and photographing in the Sandia Mountains, is grateful for the changes wrought by Hurricane Ike.
“When I came here, everything worked out better than I thought,” Beswick says. “It has been a lot easier for me to make connections and build this team here. People are friendly, willing to help and willing to collaborate. Somehow, this environment really works for me.”