Distinguished Scientist Seminar Series featuring Victoria DeRose, PhD – “Perturbing the Nucleolus with Platinum Anticancer Compounds”

Distinguished Scientist Seminar Series

Victoria DeRose, PhD
Head & Professor, Department of Chemistry and Biochemistry
University of Oregon

Location: New Research Building Auditorium and via Zoom (https://georgetown.zoom.us/j/95197826709)

Title & Abstract:

“Perturbing the Nucleolus with Platinum Anticancer Compounds”

Platinum compounds such as cisplatin and oxaliplatin are in broad clinical use. While highly effective against certain cancers, efficacy is limited by toxicity and resistance against these small metal compounds. We and others have shown extensive interactions of platinum (Pt(II)) compounds with cellular RNAs, demonstrating potential for therapeutic Pt(II) compounds to act outside of the textbook DNA damage response.  One remarkable example is the ability of oxaliplatin-like Pt(II) compounds to specifically induce the nucleolar stress response. The nucleolus is the manufacturing site for ribosomes and a hub of cell signaling. Structure-function and mechanistic studies indicate a surprising sensitivity of nucleolar effects on Pt(II) ligand size and other properties, suggesting that a relatively specific interaction is disrupted by platinum compounds that cause nucleolar stress. Current efforts include high resolution expansion microscopy to track nucleolar morphology, and building on our click-enabled Pt(II) compound library as tools for target identification, with an aim to determine the molecular mechanisms of action of these small molecule platinum compounds that specifically induce nucleolar stress.