Brian Manning

Brian Manning has made seminal contributions to understanding the TSC1/TSC2 tumor suppressor complex and its role as a critical regulator of mTORC1. His research established the biochemical mechanism by which the TSC complex functions as a GTPase-activating protein for Rheb, placing mTORC1 activation downstream of the TSC tumor suppressors and integrating AKT signaling into mTOR pathway control. He discovered that AKT phosphorylates and inactivates TSC2, mechanistically connecting PI3K/AKT and mTOR signaling. His work on TSC biology has been foundational to understanding hyperactivation of mTOR in TSC syndrome and in cancer through PTEN loss.