Elda Grabocka, PhD
Elda Grabocka, PhD
PhD, Structural Biology and Molecular Pharmacology, 2007
BS, Biology, Washington College
Most Recent Peer-Reviewed Publications
- RAS-mediated tumor stress adaptation and the targeting opportunities it presents
- Evaluating stress granules in pancreatic cancer in vitro and in vivo
- Mutant KRAS Enhances Tumor Cell Fitness by Upregulating Stress Granules
- Histological image processing features induce a quantitative characterization of chronic tumor hypoxia
- Mitotic-dependent phosphorylation of leukemia-associated RhoGEF (LARG) by Cdk1
Research in the Grabocka lab is centered on uncovering unique vulnerabilities of RAS-driven cancers and how to exploit them for the development of novel therapeutic targeting strategies.
Activating mutations in one of the RAS genes (KRAS, NRAS, or HRAS) drive the development of approximately 30% of all human cancers including cancers of the pancreas, colon, and lung. A major focus of the Grabocka laboratory is to decipher the contribution of aberrant RAS signaling to the development of pancreatic cancer. ~ 90% of pancreatic cancer patients present activating mutations in the KRAS gene. Unfortunately for patients, these tumors are very aggressive and highly resistant to standard chemotherapy. Additionally, targeted therapy options are completely lacking. We are interested in defining how mutant RAS coerces stress adaptation mechanisms of cancer cells and the tumor microenvironment to promote tumor progression and drug resistance. To this end, significant effort in the Grabocka laboratory is dedicated to understanding how mutant RAS regulates the formation of stress granules, a cellular process we have linked to the drug resistance of KRAS-driven tumors. Ongoing studies in the lab include the establishment of 3D cell culture models and mouse models to study the role of stress granules in the drug resistance of KRAS tumors, the elucidation of the molecular pathways that drive stress granule formation in cancer, and the identification of molecular targets that are candidates for therapeutic intervention. Additional research interests include the cooperation of oncogenic signaling and stress stimuli to promote the acquisition of pro-tumorigenic properties, as well as the reprogramming of the DNA damage response signaling pathways in RAS-driven cancers.