The body’s normal function depends upon maintaining energy balance matching demand and supply. The body senses its energy status by monitoring metabolite concentrations. I have discovered a metabolite that controls multiple enzymes critical for energy homeostasis and appetite in the body that may provide new approaches to tackle obesity related disease. I have found the metabolite-binding pocket in many proteins and it may represent a major new regulatory network.
Investigating The Substrate Specificity Of The Master Kinase LKB1 And The Pharmacological Targeting Of Its Substrate NUAK2 To Treat Cancers
Funder
National Health and Medical Research Council
Funding Amount
$384,768.00
Summary
Kinases are key regulators of cell signaling and emerging drug targets. LKB1 kinase specifically activates a set of substrates to modulate cellular processes, and its substrate NUAK2 is a novel target for cancer. I will elucidate the structural basis of how LKB1 recognizes its substrates and develop inhibitors targeting LKB1-NUAK2 interaction for cancer treatment. My project will provide key insights into kinase-dependent signaling and establish a new framework for therapeutics development.
Assembly And Function Of Two Interacting Oncogenic Scaffolds
Funder
National Health and Medical Research Council
Funding Amount
$705,585.00
Summary
Aberrant signaling by the protein kinase superfamily is a known driving force for many cancers and inflammatory diseases. Recently, a subset of kinase-like proteins, termed pseudokinases, have emerged as crucial regulators of kinase signalling pathways. This proposal focuses on elucidating the scaffolding function and assembly of two pseudokinases, termed SgK223 and SgK269, which display oncogenic properties and aims to understand how their signalling abilities are subverted in a disease state.