Key research themes
1. How do structural and molecular mechanisms govern ion binding, transport, and regulation in Na+/K+-ATPase?
This research area focuses on uncovering the detailed molecular architecture and dynamics of the Na+/K+-ATPase (NKA) protein complex that underlie its ability to selectively bind and transport Na+ and K+ ions. Understanding the protonation states of key residues, isoform-specific ion affinities, conformational changes during ion occlusion and release, and the impact of disease mutations elucidate the enzyme's transport mechanism and regulatory potential. Such insights advance foundational knowledge critical for drug targeting and treatment of related diseases.
2. How is Na+/K+-ATPase regulated through interaction with signaling molecules, post-translational modifications, and cellular trafficking to control physiological functions?
This theme investigates the multidimensional regulation of Na+/K+-ATPase activity beyond ion transport catalysis, focusing on how its signaling functions are modulated by phosphorylation, carbonylation, redox modifications, complex formation with kinases like c-Src, and trafficking dynamics. Such regulatory processes affect cellular ion homeostasis, sodium reabsorption in renal epithelia, cardiac and skeletal muscle excitability, and pathophysiology in diseases. Understanding these regulatory axes guides strategies for therapeutic intervention targeting NKA in metabolic, cardiovascular, and renal contexts.
3. How do tissue-specific isoforms and physiological states modulate Na+/K+-ATPase function and adaptation in muscle and epithelial tissues?
This area examines Na+/K+-ATPase isoform expression patterns, kinetic properties, and regulatory mechanisms in diverse tissues such as skeletal muscle and intestinal epithelium and their adaptations during development, exercise, and aging. Understanding isoform-specific kinetic parameters (like substrate affinities), expression changes during epithelial cell maturation, and regulation by cellular factors (extracellular K+, AMPK, PGC-1α) illuminates isozyme specialization for tissue-specific demands and informs therapeutic strategies for related dysfunctions.