School of Medicine Coronavirus Update:
Read for more details specific to medical students and School of Medicine events.


SundaramJiang Liu, MD, PhD
Associate Professor

Research Interest

My research has focused on the roles of endogenous cardiotonic steroids, oxidative stress and Na/K-ATPase signaling transduction on renal sodium handling, salt-sensitive hypertension as well as renal/cardiac fibrosis and organ remodeling. Recently, we demonstrated that cardiotonic steroids signaling through the Na/K-ATPase generated ROS is essential for the overall Na/K-ATPase signal transduction, as well as that the Na/K-ATPase α1 subunit and c-Src form a signaling complex under native resting condition. We have also demonstrated the relevance of the Na/K-ATPase signaling mediated oxidant amplification loop to the pathophysiology of renal and cardiovascular diseases and salt sensitivity.

Cardiotonic steroids and the Na/K-ATPase signaling: This part of research focuses demonstrated that cardiotonic steroids (also known as endogenous digitalis-like substances such as ouabain) mediated Na/K-ATPase signaling pathways in cardiomyocytes and renal proximal tubular cells. My work, along with others, demonstrated that the Na/K-ATPase functions not only as a classic “ion pump” but also as a “signaling pump”. The signaling function of the Na/K-ATPase is independent of changes in intracellular Na+ concentration and is regulated by protein-protein interactions.

The Na/K-ATPase signaling and salt-sensitivity: This part of research demonstrated that the Na/K-ATPase signaling mediated endocytosis of the Na/K-ATPase and sodium/hydrogen exchanger isoform 3 (NHE3) is strongly implicated as causative of experimental Dahl salt-sensitive hypertension. Specifically, cardiotonic steroids and/or reactive oxygen species (ROS), signaling through Na/K-ATPase, stimulate coordinated redistribution of Na/K-ATPase and NHE3 in renal proximal tubule, leading to stimulation of total and fractional sodium excretion.

ROS and the Na/K-ATPase signaling: This part of research demonstrated that ROS is required and involved in the Na/K-ATPase signaling in a feed-forward mechanism. Two amino acid residues were identified that undergo direct protein carbonylation modification which is critical to the Na/K-ATPase signaling.

The Na/K-ATPase signaling and renal/cardiac fibrosis: This part of research demonstrated that cardiotonic steroids and ROS mediated Na/K-ATPase signaling causes fibrosis and organ remodeling of kidney and heart, in our rat and mouse 5/6 partial nephrectomy (PNx) models. These effects were significantly attenuated by administration of antibodies against cardiotonic steroids, an active peptide blocking Na/K-ATPase signaling and other manipulations. We also identify a Na/K-ATPase signaling mediated oxidant amplification loop in the processes.