First-year Watson School student Jackie Giovanniello loves country music. We’ve learned this not so much from Jackie but from her classmates who either now love country music too, or who refuse to ride in her car because of her strict country-only radio policy. Jackie comes from Brooklyn, not an area considered by many to be very “country.” But somewhere along her journey through Providence, Rhode Island, where she attended Brown University as an undergraduate; Manhattan, where she worked at Memorial Sloan Kettering Cancer Center as a research technician; and now Cold Spring Harbor, where she’s started her Ph.D. at the Watson School, Jackie developed an appreciation for the country greats like Tim McGraw and the Dixie Chicks.
Jackie recently completed her first laboratory rotation, working in Associate Professor Raffaella Sordella’s group at CSHL. Raffaella’s lab has discovered an alternate version of one of the most well studied tumor-suppressors, p53. The variant, which the group named p53psi, doesn’t act like a tumor-suppressor at all. Instead, it reprograms cells toward a cancer phenotype, and is found in highly metastatic tumors. p53psi also increases reactive oxygen inside the cells’ mitochondria. Reactive oxygen species are a by-product of cell metabolism, and so when Jackie joined Raffaella’s group, she decided to find out if p53psi disrupted normal metabolic pathways.
Cancer cell metabolism turns out to be very different than the metabolism of normal cells. Cancer cells switch from the usual pathway of energy production—oxidative phosphorylation—to a much less efficient pathway—aerobic glycolysis. They also make more fatty acids and have faster rates of glutamine metabolism. All of these changes help make the cells resistant to many anti-cancer drugs. Jackie found that cells expressing p53psi had the sorts of metabolic changes that are associated with highly tumorigenic cancer cells. But how p53psi generates these changes in metabolism is still unclear. Normal p53 binds DNA to control which genes are expressed, but p53psi cannot do this. Cells that have p53psi are different than cells with mutations in p53, which eliminate its function completely. Therefore, Jackie and Raffaella think that p53psi has gained a new role in the cell—distinct from its DNA binding function—that results in changes in metabolism, reactive oxygen production, and ultimately aggressive metastases.
Jackie’s interest in cancer began before she arrived at CSHL. Her work with Drs. Neal Rosen and Sarat Chandarlapaty at Memorial Sloan Kettering Cancer Center focused on the signaling pathways that regulate cell growth and thus contribute to the uncontrolled growth associated with tumors. Jackie studied a well-known growth pathway in breast cancer cells to discover why some inhibitors of the pathway cause the cancer cells to die, whereas other inhibitors of the same pathway do not. The difference—a molecule in one branch of the signaling pathway—pointed to a potential new therapeutic target.
In graduate school, Jackie wants to continue to work on questions that will help develop better treatment options for patients. After her first rotation in the Sordella lab, Jackie has moved on to study neuropsychiatric disorders in Associate Professor Bo Li’s lab. She’s trying to understand how different populations of neurons in the brain contribute to the development of fear memories, with the hopes of helping to determine how these processes become dysregulated in anxiety and post-traumatic stress disorders. When asked how Jackie became interested in neuroscience, she said, “Science has made great gains in understanding disease below the head, but there’s still so much work to do to understand and treat mental illnesses in the same way. Better understanding of the biological bases of these disorders will help diminish the stigma associated with them, while also accelerating development of better treatments.”
When she’s not training mice, Jackie continues to promote country music around the CSHL campus, which is maybe not such an unlikely place to find converts. As Jackie points out, “most country music tells a story. It’s about hard-working people trying to better their communities.” This is true for many of us here at the Watson School.
In the future, Jackie hopes to work in science policy, integrating what she’s learned as a scientist with her interests in politics and science outreach. In the meantime, she’s still working on converting all you country non-believers out there.