Investigating AKT1-dependent pathways to regulate cellular metabolism

The serine/threonine kinase AKT1 is a key mediator of cell growth and survival processes including glucose metabolism, apoptosis, transcription, proliferation, and migration. AKT1 is activated by phosphorylation at two key regulatory sites, Threonine308 and Serine473, that are both used as clinical diagnostic markers for cancer. AKT1 also plays an important role in glucose metabolism by inhibiting glycogen synthase kinase-3 (GSK-3) isoforms through phosphorylation. I will investigate AKT1-dependent changes in the mammalian metabolome and glucose metabolism specifically in collaboration with the laboratory of Dr. Karsten Hiller (U. Braunschweig), I will monitor the metabolic profiles of multiple mammalian and cancer cell lines transfected with inactive AKT1 or active AKT1 with programmed phosphorylation at one or both regulatory sites. Leveraging the expertise of the Hiller lab in glucose metabolism and quantitative metabolomics, identification of metabolites and constituents of glucose metabolism that respond to differentially phosphorylated AKT1 will be carried out. Together, the data will reveal new target substrates for AKT1, and metabolites that are diagnostic for hyper-active AKT1, which hallmark of cancer that occurs in 50%human tumors.

Faculty Supervisor:

Patrick O’Donoghue

Student:

Partner:

Technische Universitat Braunschweig

Discipline:

Life Sciences

Sector:

Education

University:

The University of Western Ontario

Program: