PI: Daniel Anderson, Department of Chemical Engineering, MIT
PI: Konstantin Piatkov, Center for Data-Intensive Biomedicine and Biotechnology, Skoltech
The main goal of this proposal is the validation of N-end rule dependent ubiquitin ligases as new targets for cancer therapies. Using animal models we will investigate the role of these ubiquitin ligases in the context of the most common liver cancer – hepatocellular carcinoma (HCC). Specific Aims:
Aim 1: To study the role of the N8 end rule dependent ubiquitin ligases Ubr1, Ubr2, Ubr4 and Ubr5 in the normal adult liver.
Aim 2: to study the role of the N8end rule dependent ubiquitin ligases Ubr1, Ubr2, Ubr4 and Ubr5 in the development and maintenance of hepatocellular carcinoma using spontaneous and implanted orthotopic mouse models.
Aim 3: to investigate the modulation of the N-end rule in vivo as a new therapy for HCC, by modulating the expression of Ubr1, Ubr2, Uvr4 and Ubr5 using siRNAs delivered directly to the liver via lipid nanoparticles.