Steven N. Ebert, PhD
Department of Pharmacology
Georgetown University Medical Center
Room 295, Building D
3900 Reservoir Road, NW
Washington, DC 20057
Phone: 202 687-1270
Fax: 202 687-2585
Sex steroid hormones and drug-induced arrhythmias
My research interests focus on molecular signaling mechanisms that regulate cardiac development and function. Specifically, we are interested in learning how hormones and other signaling molecules modulate cardiac function. A major emphasis is placed on the role of sex steroid hormones in regulating potassium channels in the heart. This is an important area of investigation because the potassium channels are critical for cardiac repolarization. Drugs and/or genetic mutations that impair the function of potassium channels in the heart lead to delayed repolarization and increased risk of developing life-threatening ventricular arrhythmias. Remarkably, these arrhythmias develop far more often in women than in men (2:1 ratio).
Our recent studies have shown that androgen hormones such as dihydrotestosterone appear to “protect” the heart from drug-induced cardiac arrhythmias by increasing the activity of key potassium channels in ventricular myocytes. Our current efforts are focused on determining how androgen hormones regulate these potassium channels. To accomplish this, we are evaluating the expression profiles of specific genes that encode for potassium channel subunits and other proteins that are known modulators of potassium channel function in the absence and presence of androgen hormones. In addition, we are utilizing gene chip microarrays to determine how androgen hormones influence global patterns of gene expression in cardiac myocytes. Finally, we are using transient co-transfection experiments to evaluate the role of the androgen receptor and its cardiac-specific co-activator, FHL2, in the regulation of these genes.
Our long-term goals are to provide a framework for understanding how androgens and other hormones influence cardiac development and function, with the hope that this information will be utilized to help lower the incidence and severity of adverse cardiac reactions to drugs in women (and men).
- Liu XK, Katchman A, Whitfield BH, Wan G, Janowski EM, Woosley RL, Ebert SN. In vivo androgen treatment shortens the QT interval and increases the densities of inward and delayed rectifier potassium currents in orchiectomized male rabbits. Cardiovasc Res. 2003 Jan; 57 (1):28-36.
- Katchman AN, McGroary KA, Kilborn MJ, Kornick CA, Manfredi PL, Woosley RL, Ebert SN. Influence of opioid agonists on cardiac human ether-a-go-go-related gene K(+) currents. J Pharmacol Exp Ther. 2002 Nov; 303(2):688-94.
- Ji S, Tosaka T, Whitfield BH, Katchman AN, Kandil A, Knollmann BC, Ebert SN. Differential rate responses to nicotine in rat heart: evidence for two classes of nicotinic receptors. J Pharmacol Exp Ther. 2002 Jun; 301(3):893-9.
- Casimiro MC, Knollmann BC, Ebert SN, Vary JC Jr, Greene AE, Franz MR, Grinberg A, Huang SP, Pfeifer K. Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange-Nielsen Syndrome. Proc Natl Acad Sci U S A. 2001 Feb 27; 98(5):2526-31.
- Liu XK, Wang W, Ebert SN, Franz MR, Katchman A, Woosley RL. Female gender is a risk factor for torsades de pointes in an in vitro animal model. J Cardiovasc Pharmacol. 1999 Aug; 34(2):287-94.