Projects
The Marsiglia Lab uses biochemical, cellular, biophysical, and synthetic approaches to understand the biology of normal and oncogenic PI3K-AKT signal transduction, and the role of clinical kinase inhibitors in altering protein-protein interactions in the PI3K-AKT pathway. The ultimate goal of the lab is to use this knowledge to design better inhibitors for the treatment of cancer.
Mapping the pharmacology of protein-protein interactions in the PI3K-AKT pathway
The PI3K-AKT pathway is one of most highly dysregulated pathways in cancer. Drugs targeting this pathway generally focus on inhibiting single proteins, however acquired and adaptive resistance resulting in the loss of drug efficacy are common. The Marsiglia Lab studies alternative approaches focused on understanding the role that AKT inhibitor binding has on protein-protein interactions, and how it ultimately leads to drug efficacy.
Determining the structural basis of PI3K-AKT pathway signaling
It is becoming increasingly evident that signal transduction occurs through large macromolecular complexes instead of a linear chain of protein-protein interactions. The Marsiglia Lab aims to understand the structural basis of oncogenic PI3K-AKT signaling using an array of structural techniques including X-ray crystallography, cryo-EM, and NMR Spectroscopy.