Two transmembrane signaling receptors mediate the in vivo effects of the renin angiotensin system. Of these two, the Angiotensin II (AngII) type 1 receptor (AT1R) plays an indispensable role in physiological regulation of blood pressure and water-electrolyte balance. Pathological states such as hypertension, cardiac hypertrophy and heart failure (HF) are observed when AT1R activation becomes chronic. The AT1R is a target for classical sartan-family of antihypertensive drugs. Currently these drugs are indicated for treatment of additional disease conditions such as myocardial infarction, aortic aneurism, Marfan syndrome and diabetic nephropathy and retinopathy, which makes the sartans a target for continued drug development. AT1R is a member of G-protein coupled receptor (GPCR) family, which are transmembrane proteins that transform extracellular hormonal or physical cues into specific amplified intracellular signals.
We study all aspects of AT1R structure, function, physiology, genetics and signaling. The approaches we use include transgenesis, molecular pharmacology, ligand design, membrane protein biochemistry, protein-protein interaction, signal transduction, gene regulation, micoRNA regulation, proteomics and post-translational modifications.