- Location: Medical Research Building (MRB) II (Preston Cancer Research Building) • 465 21St Ave S • Nashville, TN 37232
- Room: 206
- Contact: Stephen Doster
- Email: firstname.lastname@example.org
- Phone: 936-3883
- Website: https://medschool.vanderbilt.edu/basic-sciences/discovery-sciences-emerging-scholars-lectures
Please join us for the next Discovery Sciences Emerging Scholars Lecture on Tuesday, November 13 at 4:00 pm in 206 Preston Research Building. Luisa Escobar-Hoyos, a Postdoctoral Research Fellow at Memorial Sloan Kettering Cancer Center and Research Assistant Professor at Stony Brook University will discuss her pancreatic cancer research: “Targeting RAS and mutant p53: Discovery of RNA splicing as a therapeutic vulnerability in pancreatic cancer”
We recently discovered a novel mechanism of cooperation between the two most common oncogenes in pancreatic cancer, oncogenic RAS and neomorphic mutant p53, uncovering a potential therapeutic opportunity to target tumors that bear these mutations. Specifically, we found that mutant p53 causes aberrant splicing of GAP proteins, the negative regulators of RAS, resulting in expression of inactive GAP proteins (polyC GAPs), and ultimately promoting oncogenic RAS signaling. In addition, we identified that pancreatic tumors in mouse models depend on expression of polyC GAPs and splicing machinery proteins, as genetic and chemical inhibition of these proteins caused decrease in tumor growth, number of metastases and tripled the survival time of animals. These studies identified these proteins as new targets for tumors with neomorphic p53 and oncogenic KRAS. We expect to identify novel and specific dependencies of PDAC cells by studying and targeting specific alternatively spliced products and/or manipulating the function of splicing factors in the background of multiple forms of mutated TP53, to provide the foundation for future research that will lead to the development of more effective approaches to treat PDAC patients, improving their survival and quality of life.