- Ph.D., Sherbrooke, Canada, 1997
The long-term goal of Dr. Duan's Laboratory of Cardiovascular Phenomics is to determine the molecular mechanisms for the functional role of ion channels in the cardiovascular system in the context of health and disease. Ion channels are membrane-spanning proteins which form pores for ion permeation and are the major catalysts of many biological functions. Activation of ion channels can produce significant effects on cardiac electrical activity (automaticity and action potential) and contractile function (excitation-contraction coupling). In addition, ion channels are important regulators of acidification of intracellular organelles, cell volume, proliferation, differentiation, and apoptosis. Ion channels interact with many partners and function as an integrated "ion channel module" or "channel protein complex". Under pathological conditions "ion channel modules" often undergo remodeling and provide substrates for cardiovascular disease such as cardiac rhythm and contraction disorders and hypertension. Therefore, the study of ion channels has important significance in the translational medicine for the prevention and treatment of cardiovascular diseases. Chloride (Cl-) channels in the cardiovascular system, including the PKA- and PKC-activated CFTR Cl- channels, the volume-regulated outwardly rectifying ClC-3 and inwardly rectifying ClC-2 Cl- channels, the Ca2+-activated TMEM16 (Bestrophin and CLAC) Cl- channels, represent new targets for therapeutic agents against heart diseases. To gain mechanistic insights into the functional role of these ion channels in the context of health and disease the Duan laboratory has successfully established several animal models for cardiac diseases and hypertension and has the capacity to study the phenome-genome-proteome relationship and molecular mechanisms for cardiovascular disease at multiple levels of the whole-animal, the isolated organ, the tissue, the cell, and the molecule. The technology platforms used in the Duan laboratory include patch-clamp, molecular biology, genetics, genomics, proteomics, conditional systems for gene targeting and addition, isolated heart perfusion system, echocardiography, and telemetry system.