Graduate student Cai Roberts
Graduate student Cai Roberts is exploring a novel twist on cancer treatment that targets a unique protein. The protein, called Twist, may allow cancer cells to take some devious turns within the body.
Twist is a transcription factor, a protein that regulates gene expression. It is important for proper development in the womb, but in adults is mostly turned off in our cells. Cancer cells often reactivate it when they are stressed, which enables the cells to move around the body—in other words, metastasize. New research, however, suggests that Twist could be doing more than just letting cells move. In a tricky turn, Twist may help ovarian cancer cells resist the chemotherapy drugs most often used to treat ovarian tumors, Roberts said.
After earning a degree in biomedical engineering from UC Davis, Roberts joined the lab of Carlotta Glackin, Ph.D., associate professor in the Department of Developmental and Stem Cell Biology at City of Hope, to begin his Ph.D. work. Together, Glackin and Roberts worked on unraveling the intricacies of Twist and the way it functions in ovarian cancer.
During his research at City of Hope, Roberts, now a postdoctoral associate at the Yale University School of Medicine, found in fact that “Twist was activating signals in the cells that told the cells to keep growing and dividing despite the presence of the drug.”
In another project, he examined the function of one unique part of the Twist protein not found in any other human proteins. He showed which individual amino acids were responsible for Twist being able to bind to other proteins, particularly one called p65.
“I showed that this binding could be blocked by an inhibitor I designed, suggesting that drugs targeting Twist could eventually be developed,” he said.
For a final project, he worked with two other graduate students, along with collaborators at City of Hope and UCLA, to reduce the levels of Twist in cancer cells.
“To do this, we used short interfering RNA (siRNA) that bound to the Twist RNA and prevented it from ever being translated into protein,” he explained. “To deliver the siRNA into cells, we used nanoparticles designed by our collaborators. Using these particles and our siRNA, we drastically reduced Twist expression in breast, ovarian and skin cancer cells. We also showed that this treatment could reduce the size of melanoma tumors and make ovarian tumors sensitive to chemo again.”
“I very much enjoyed working at City of Hope,” Roberts said. “Dr. Glackin encouraged me to pursue my ideas even if they were outside her areas of expertise. This was made easier by how open City of Hope researchers are to collaboration, and I was able to learn both in the lab and in the classroom from experts in a number of fields. Working next to the hospital, and seeing the patients on campus, put human faces to the work we were doing, and it was incredibly satisfying knowing that the work we were doing could soon help these patients and those like them.”
At Yale, Roberts is researching mechanisms of drug resistance in ovarian cancer recurrence.
“Here, I am examining the links between Twist, the well-known cancer gene p53, and the recurrence of ovarian cancer in patients who initially responded well to their chemotherapy,” he said. “Our laboratory has some innovative models of ovarian cancer progression in the dish, and I am helping to create new models to further the testing of our ideas and potential new treatments for ovarian cancer.”
When he finishes his postdoctoral training, he would like to run a research lab of his own, as well as teach. “New studies are finding more and more functions of Twist and similar genes, and I am interested in what determines which functions are turned on or off in different cancers at different times and under different conditions,” he said.
But it’s the opportunity to improve or even save patients’ lives that motivates him, he said. “Seeing and hearing from patients puts the struggles of research in perspective, and the chance to have an impact makes all the late nights and weekends worthwhile.”