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DAYUE DUAN, M.D., Ph.D.
Associate Professor
M.D., Hunan Medical University 1982;
Ph.D., McGill 1996
Location: Manville 9D
Email: dduan medicine.nevada.edu
Tel: 775 784-4738
Fax: 775 784-1620
Research Interests
Ion channels, functional genomics and proteomics, cardiac electrophysiology and pharmacology, cardiac ischemia, cardioprotection, myocardial hypertrophy and heart failure.
Research Summary
The long-term goal of Dr. Dayue Duan's Laboratory of Functional Genomics and Proteomics is to determine the molecular mechanisms for the functional role of ion channels in the heart.
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. Under pathological conditions ion channels often undergo remodeling and provide substrates for cardiac rhythm and contraction disorders. Therefore, the study of ion channels has important clinical significance for cardiovascular diseases.
We hypothesize that ion channels function as an integrated "ion channel module" or "channel protein complex" in the context of health and disease. To test this hypothesis, in collaboration with colleagues in the Center of Biomedical Research Excellence (COBRE) and School of Medicine, we have developed a multitude of approaches ranging from the molecular to the integrated level, including molecular biology, genetics, genomics, proteomics, conditional systems for gene targeting and addition, patch-clamp, isolated heart perfusion system, echocardiography, and telemetry system. Several animal models of heart diseases in wild-type and transgenic mice have been established in the laboratory and are currently utilized to delineate the molecular mechanisms of physiological and pathophysiological function of several anionic and cationic channel modules in the heart.
Anionic (Cl-) channels in the heart represent new targets for therapeutic agents against heart diseases. Previous work from ours and others revealed that at least 4 different Cl- channels are expressed in the heart. The PKA- and PKC-activated Cl- channels are encoded by CFTR. The volume-regulated outwardly rectifying and inwardly rectifying Cl- channels may be encoded by ClC-3 and ClC-2, respectively. The Ca2+-activated Cl- channels might be encoded by CLCA or Bestrophin. Our current focus is to further determine what exact role of each Cl- channel is in cardiovascular function and whether Cl- channel mutations cause human cardiovascular diseases.
In response to pathological stress such as myocardial hypoxia, ischemia and reperfusion, myocardial hypertrophy and heart failure, adaptive remodeling of the cardiac myocytes is closely associated with perturbations of both cell volume and ion channel function. In addition to ClC-3 and ClC-2 chloride channels, the A-type K+ channels are also strongly regulated by cell volume changes. Therefore, the molecular mechanisms and the physiological and pathophysiological consequences of volume regulation of these ion channels in the heart are currently under investigation in our laboratory.
View the publications of Dr Duan on PubMed
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