Fluorescent Probes for Live-Cell Imaging of Sirtuin Activity: Applications to Breast Cancer

Type of Award: Catalyst
Date Awarded: September 2015
Award End Date: August 2017
Amount Awarded: $ 200,000.00
PI(s): Bryan Dickinson, PhD, UChicago; David Gius, MD/PhD, NU;

Abstract: Personalized cancer therapy identifies subgroups of patients who will benefit from specific therapies strategies. The Gius lab has identified a subgroup of estrogen positive (ER+) luminal B human breast cancer that exhibits decreased SIRT3 expression or monoallelic deletion using murine models and human breast cancer samples, suggesting SIRT3 is a new target for therapeutic strategies. However, the role of SIRT3 activity in disease progression is unknown, in large part to due a dearth of tools for measuring endogenous activity. The Dickinson lab will design and synthesize a new class of chemical fluorescent probes to measure SIRT3 lysine deacetylation in living systems. Both labs will work together to validate each new tool using in vitro analyses, cell culture, and in vivo murine models. Together, both labs will apply the probes to uncover the mechanistic roles of SIRT3 in breast carcinogenesis, aiming to eventually use these new tools and models to investigate novel therapeutic predictors.