Key research themes
1. How do conformational states and binding site features of receptor kinase domains influence selective inhibition and drug resistance?
This research theme focuses on the structural dynamics of receptor kinase activation states—particularly the active (DFG-in) and inactive (DFG-out) conformations—and how these conformations define the binding modes and selectivity profiles of small-molecule kinase inhibitors. Understanding these molecular features is crucial for rational drug design that overcomes cross-reactivity and acquired resistance mechanisms in cancer therapies.
2. What are the mechanisms and specificity determinants of receptor tyrosine kinase activation and substrate phosphorylation, including autophosphorylation and downstream signaling?
This theme examines the molecular basis of receptor tyrosine kinase (RTK) activation, including autophosphorylation in activation loops and C-terminal tails, and how these phosphorylation events modulate kinase catalytic activity and substrate specificity. It also explores kinase-substrate recognition motifs, docking interactions, and phosphorylation site preferences that determine specificity in complex signaling networks. These mechanisms underpin the regulation of cellular functions such as proliferation and survival, with implications for targeted therapeutics.
3. How can large-scale proteomic and interactome mapping advance understanding of receptor tyrosine kinase regulation and kinase-phosphatase networks?
Focused on systems-level studies, this theme integrates mass spectrometry-based phosphoproteomics, protein-protein interaction mapping, and inhibitor profiling to construct comprehensive regulatory networks involving receptor tyrosine kinases (RTKs), their substrates, and interacting phosphatases. These approaches enable identification of kinase-substrate relationships, kinase co-regulation patterns, and phosphatase-mediated control mechanisms, providing crucial insights into signaling complexities, resistance mechanisms, and potential combinatorial therapeutic targets.