Han-Gang Yu, Ph.D. Associate Professor of Physiology and Pharmacology Graduate Training: State University of New York at Stony Brook Fellowship: State University of New York at Stony Brook
	Office: 3065-HSN Lab: 3034-HSN PO Box 9229 Morgantown, WV 26506	Email: hyu@hsc.wvu.edu Phone: 304-293-2324 Fax: 304-293-5513

Research Interests:

Cardiac death is the endpoint of many diseases including diabetes, particularly in patients that are overweight and obese. Cardiac arrhythmias (defined as abnormal electrical activity in the heart) are direct causes of sudden cardiac death. Currently, we are focused on understanding of two conditions related to arrhythmias.

Project-1: Mechanisms of Cardiac Bradycardia
Sick sinus syndrome is a bradycardia-tachycardia syndrome, manifested by bradycardia. Bradycardia is slow heart rate (<60 beats per minute). Severe bradycardia requires implantation of electronic pacemaker. There is no pharmacological treatment. If untreated, bradycardia can evolve into atrial fibrillation, the most common arrhythmia in clinic; it can also develop to ventricular arrhythmias, the less common but lethal leading to sudden cardiac death.
Why is there no alternative pharmacological treatment for bradycardia? The answer is due to the unknown mechanisms that cause the disease. Recently, mutations in a protein called pacemaker channel have been found and directly linked to patients with bradycardia accompanied with atrial fibrillation and ventricular tachyarrhythmia. We are studying and developing the molecular tools to correct the mutated channel with hope to translate our findings to the future treatment of bradycardia.

Project-2: Long-QT in Obesity induced Insulin Resistance
Prolongation of QT interval on electrocardiogram (ECG) is an independent predictor of high cardiovascular risk in type 2 diabetic patients that are overweight or obese. Close to 75% of insulin resistant patients die of heart disease. How does an obesity-induced insulin resistant heart develop long-QT remains an open question.
We have made initial findings of one ion channel that is dysfunctional in an obesity-induced insulin resistant animal model, leading to long-QT. We are hoping that our findings may find applications in treatment of cardiac arrhythmias associated with diabetes patients.

Selected Publications:

• Yen-Chang Lin, Jianying Huang, Qi Zhang, John M. Hollander, Jefferson C. Frisbee, Karen H. Martin, Casey Nestor, Robert Goodman, Han-Gang Yu. Inactivation of L-type Calcium Channel modulated by HCN2. AJP-Cell (in Press), 2010.
• Yen-Chang Lin, Jianying Huang, Kan Hong, Jefferson Frisbee, Han-Gang Yu. Rescue of a Trafficking Defective Human Pacemaker Channel via a Novel Mechanism: Roles of Src, Fyn, Yes tyrosine kinases. J. Biol. Chem. 284:30433-30440, 2009.
  Han-Gang Yu, Jianying Huang, Yen-chang Lin. Non-proteolytic HCN2 in the heart. J. Biol. Chem. 284, le7, 2009
  Han-Gang Yu, Racing of biological pacemaker, Recent Patents on DNA & Gene Sequences (invited review), 3:193-200, 2009.
• Jefferson C. Frisbee, John M. Hollander, Robert W. Brock, Han-Gang Yu, and Matthew A. Boegehold. Intergration of skeletal muscle resistance arteriolar reactivity for perfusion responses in the metabolic syndrome. Am J Physiol Regul Integr Comp Physiol 296: R1771-1782, 2009.
• Qi Zhang, Aijie Huang, Han-Gang Yu. Associated Changes in HCN2 and HCN4 Transcripts and I(f) Pacemaker Channels in Myocytes. BBA-Biomembrane, 1788:1138-1147, 2009.
• Jianying Huang, Aijie Huang, Qi Zhang, Yen-Chang Lin, and Han-Gang Yu. Novel Mechanism for Suppression of Hyperpolarization-activated Cyclic Nucleotide-gated Pacemaker Channels by Receptor-like Tyrosine Phosphatase-a. J. Biol. Chem.  283: 29912-29919, 2008.
• Chenhong Li, Qi Zhang, Bunyen Teng, S. Jamal Mustafa, Jianying Huang, and Han-Gang Yu (2008). Src Tyrosine Kinase Alters Gating of Hyperpolarization-Activated HCN4 Pacemaker Channel through Tyr531. Am J Physiol Cell Physiol 294:C355-C362.
• Xiao Yu; Lijun Yao; Peng Zhou; Ying Li; Hui Zheng; Liang-Hong Zheng; Iain Bruce; Jun-Bo Ge; Shi-Qiang Wang; Han-Gang Yu (co-Corresponding Author ); Zhuan Zhou (2007). Calcium influx through I f channels in rat ventricular myocytes. Am. J. Physiology: Cell Physiol. 292: C1147-C1155, 2007.
• Arinsburg SS, Cohen IS, Yu HG (2006). Constitutively active Src tyrosine kinase changes gating of HCN4 channels through direct binding to the channel proteins. J. Cardiovascular Pharmacology 2006; 47: 578-586.
• Yu H, Lu Z, Pan Z, Cohen IS (2004). Tyrosine kinase inhibition differentially regulates heterologously expressed HCN channels. Pflugers Archive 447(4):392-400.
• Yu X, Duan KL, Shang CF, Yu H, Z. Zhou (2004). Calcium influx through hyperpolarization-activated cation channels (Ih channels) contributes to activity-evoked neuronal secretion. Proc. Nat. Acad. Sci. USA 101(4):1051-1056.
• Plotnikov AN, Yu H (equal contributor), Geller JC, Gainullin RZ, Chandra P, Patberg KW, Friezema S, Danilo, P, Cohen IS, Feinmark S, Rosen MR. (2003). The role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart. Circulation 107:2844-2849.
• H. Yu , J. Wu, I. Potapova, R.T. Wymore, B.Holmes, J. Zuckerman, Z. Pan, H.Wang, W. Shi, R.. Robinson, M.R. El-Maghrabi, W. Benjamin, J. Dixon, D. McKinnon, I.S. Cohen, and R. Wymore. (2001) MinK-related peptide 1: a beta subunit for the HCN ion channel family, enhances expression and speeds kinetics. Circulation Research 88: e84 - e87.
• Hangang Yu , Michael R. Rosen, Susan Steinberg, Hong-Sheng Wang, Junyuan Gao, Randy S. Wymore, and Ira, S. Cohen (2000). Effects of the Regin-Angiotensin System on the current ito in epicardial and endocardial ventricular myocytes from the canine heart. Circulation Research 86, 1062-1068.

Lab Personnel: Jianying Huang - Graduate Student Yen-Chang Lin - Graduate Student
	Yen-Chang Lin and Jianying Huang