BUA senior Robbie Mulroy’s thesis project has the potential to impact the future of cancer research.
For his senior thesis, Robbie ’24 is investigating the role of the CREB binding protein (CBP) in cancer under the guidance of BU Biology Professor Dr. Trevor Siggers as well as BUA Biology Teacher Dr. Colleen Krivacek, who by remarkable coincidence happens to have expertise in this area. CBP is a cofactor that binds to transcription factors, which in turn bind to DNA to regulate when genes are expressed. The CREB binding protein regulates around 10,000 different genes; Robbie has been studying where and when CBP’s five binding regions bind to various transcription factors.
Inspired by his BU biology courses, Robbie was motivated to better understand the inner workings of the human body on a genetic level, and to investigate CBP’s effect on the immune system and the relationship between CBP and tumor development.
In the spring of 2023, Robbie reached out to Dr. Siggers to introduce himself and to ask if Dr. Siggers might be willing to supervise his senior thesis research. Dr. Siggers happily accepted, and Robbie spent the summer in the Siggers Lab here on campus, which is dedicated to systems biology and gene regulation in the immune system. Conducting experiments alongside undergraduate and graduate students, Robbie’s research entailed taking each of five binding domains and inserting them into lentivirus plasmid, infecting cells with that virus, and then extracting the nuclei of those cells. He then used a protein binding microarray to test binding domains with different transcription factors to see which ones bound and which did not. The experimentation process was not without challenges, and taught Robbie some important lessons about scientific methods and problem solving. Through trial and error, Robbie and his fellow researchers fine tuned their experiments, adjusting transformation timings and solution concentrations until they felt they were achieving valid, measurable results.
Robbie is now working on translating his findings into a research paper that will constitute his thesis project. Reflecting on potential broader impacts of his very technical research, Robbie explains:
“Errors in CBP regulation are linked to many types of cancer, including lung cancer, head and neck cancer, acute leukemia, colorectal cancer, breast cancer, and prostate cancer. Through interactions with other proteins and its primary histone acetylation function, CBP regulates several phases of the cell cycle. This means that overexpression of the gene that encodes CBP or mutations within the gene can cause cells to grow unpredictably. On the flip side, the underexpression of CBP has been shown to lead to apoptosis (cell death). Some cancer treatments in development are trying to downregulate CBP expression in cancer cells to kill them.”
Future cancer researchers may build on Robbie’s and Dr. Siggers’s team’s findings to further tease out the relationship between the CREB binding protein and tumor development. Robbie will present his complete research project alongside fellow seniors at BUA’s Senior Thesis Symposium in Metcalf Hall on May 13, 2024.