• Cardiac Electrophysiology and Pharmacology
• Mechanisms and approach to treatment of cardiac arrhythmia
• Molecular genetics and mutation analysis of the basis for cardiac arrhythmias and sudden cardiac death
• Molecular and cellular characteristics of ion channels in heart
• Gene expression and modulation
• Confocal microscope and cell culture

My work involves basic and clinical research aimed at understanding the basis for the development of cardiac arrhythmias secondary to genetic mutations involving ion channels within the cells of the heart. Genetic errors in the genes that encode cardiac ion channels can lead to electrical disturbances that can cause lethal arrhythmias such as ventricular fibrillation or less life-threatening arrhythmias such as atrial fibrillation. After finding gene mutations associated with various arrhythmic syndromes such as Brugada and Long QT syndromes, I use heterologous expression of the mutated genes and voltage clamp techniques to study the nature of the dysfunction of the ion channel. When the electrical defect observed is consistent with the phenotype of the patient in the clinic, we gain confidence that the genetic variation uncovered is responsible for the disease. Using these same techniques we are able to begin a search for drug therapies that may be used to correct the abnormality in these patients.

In a recent study, we demonstrated for the first time that a mutation in SCN5A, the gene that encodes the a subunit, may be responsible for the development of repeated episodes of ventricular fibrillation, referred to as an electrical storm, in some patients experiencing a heart attack.

In other studies, we uncovered a mutation that sensitizes the heart to the antiarrhythmic drug lidocaine, causing it to unmask the Brugada syndrome, an inherited arrhythmias syndrome that leads to sudden death of young adults. In yet another study, we demonstrated the basis for the more sever clinical phenotype of family members with compound mutations responsible for the Brugada syndrome.

We also recently demonstrated that a mutation in SCN5A is responsible for conduction disease. The mutation caused a trafficking-defect, meaning that the ion channel protein produced was not properly transported to the membrane of the cardiac cell. The results provide support for the hypothesis that, in addition to the Brugada syndrome, loss of proper transport and functional expression of the hNav1.5 protein in the plasma membrane can result in cardiac conduction defects.

Recently, I have discovered BrS7. It provides evidence that a mutation in SCN3B, encoding the ?3 subunit of the sodium channel, can cause a loss of function in INa leading to a Brugada phenotype. It will assist with the diagnosis and ultimately with the approach to therapy by understanding the genetic basis for the Brugada syndrome.

Expression, purification and functional characterization of a recombinant scorpion venom peptide BmTXK?.  
Cao Zhijian, Xiao Fan, Peng Fang, Jiang Dahe, Mao Xin, Liu Hui, Li Wenxin, Hu Dan, Wang Teng.
Peptides, 2003, Feb, 24(2):187-192
PubMed ID:12668201

Effects of BmkTXK? on electrophysiological properties of rabbit atrial myocytes.
Hu Dan, Huang Congxin, Jiang Hong, et al.
Chinese Medical Journal (English), 2003, Nov, 116(11): 1691-1696
PubMed ID: 14642139

Effects of BmkTXKß on potassium currents in rabbit atrial myocytes.
Hu D, Huang C, Jiang H, Wang T
Chinese Journal of Cardiac Pacing and Electrophysiology. 2003; 17: 121-124.

Inhibitory Effect of BmkTXK? on Transient Outward Potassium Current in Rabbit Atrial Myocytes.  
Hu Dan, Huang Congxin, Jiang Hong, et al.
Progress in Biochemistry and Biophysics, 2003, Mar, 30(2):266-271

Study of a new ARA: Eplerenone.  
Jiang H, Hu D.
World Clinical Drugs, 2004; 25: 19-22

Study of Kir2.1, Kir3.4 and Kv4.3 potassium channel gene expression in atria of patients with chronic atrial fibrillation. Hu D, Huang C, Li GS, Tu ZF, Mao ZF, Wang ZW. Journal of Wuhan University (Medical Science). 2005; 2: 133-138.

Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada Syndrome.  
Cordeiro Jonathan M, Barajas-Martinez Hector, Hong Kui, Burashnikov Elena, Pfeiffer Ryan, Orsino AM, Wu Yue Sheng, Hu Dan, Brugada Joseph, Brugada Pedro, Antzelevitch Charles, Dumaine Robert, Brugada Ramon.
Circulation, 2006 Nov, 114: 2026 - 2033.
PubMed ID:17075016

Novel mutation in the SCN5A gene associated with arrhythmic storm development during acute myocardial infarction.  
Hu Dan, Viskin Sami, Oliva Antonio, Carrier Tabitha, Cordeiro Jonathan, Barajas-Martinez Hector, Wu Yuesheng, Burashnikov Elena, Sicouri Serge, Brugada Ramon, Rosso Rafael, Guerchicoff Alejandra, Pollevick Guido, Antzelevitch Charles.
Heart Rhythm, 2007 Aug, 4(8):1072-1080. Epub 2007 Apr 10
PubMed ID:17675083

Genetic predisposition and cellular basis for ischemia-induced ST segment changes and arrhythmias.  
Hu Dan, Viskin Sami, Oliva Antonio, Cordeiro Jonathan, Guerchicoff Alejandra, Pollevick Guido, Antzelevitch Charles.
Journal of Electrocardiology, 2007 November - December; 40(6S1):S26-S29.
PubMed ID:17993325

Gain of function in IKs secondary to a mutation in KCNE5 associated with atrial fibrillation 
Ravn L, Aizawa Y, Pollevick GD, Hoffman-Bang J, Cordeiro JM, Dixen U, Jensen G, Wu Y, Burashnikov E, Haunso S, Guerchicoff A, Hu D, Svendsen J, Christiansen M, Antzelevitch C. Heart Rhythm. 2008; 3:427-35. PMCID2515863.

Lidocaine-induced Brugada syndrome phenotype linked to a novel mutation and polymorphism in the cardiac sodium channel. 
Barajas-Martínez HM, Hu D (Co-first Author), Cordeiro JM, Wu Y, Kovacs RJ, Meltser H, Kui H, Burashnikov E, Brugada R, Antzelevitch C, Dumaine R. Circ Res. 2008; 103:396-404. NIHMS58188..

A mutation in the ß3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype. 
Hu D, Barajas-Martinez HM, Burashnikov E, Springer M, Wu Y, Varro A, Pfeiffer R, Koopmann TT, Guerchicoff A, Pollevick GD, Antzelevitch C. Circ Cardiovas Genet, 2009; 2:270-278.

SCN5A mutation associated with acute myocardial infarction. 
Oliva A, Hu D (Co-first Author), Viskin S, Carrier T, Cordeiro JM, Barajas-Martinez H, Wu Y, Burashnikov E, Brugada R, Rosso R, Guerchicoff A, Pollevick G, Pascali VL, Antzelevitch C. Legal Medicine, 2009,11(s1): s206-s209. PMID 19345130.

The Influence of a Calcium Channel Polymorphism on Sodium Channel Mutation-Induced Conduction Disease. 
Hu D, Barajas-Martinez HM, Nesterenko VV, Pfeiffer R, Guerchicoff A, Cordeiro JM, Curtis AB, Pollevick GD, Wu Y, Burashnikov E, Antzelevitch C. PACE, Accepted, 2009