Robert D. Harvey
Academic Unit: School of Medicine
P rofessional degrees (Degree, year, Institution): Ph.D., 1987, Northwestern
Mail Stop: 220
Biophysics, Cell Biology, Physiology, Pharmacology
The autonomic nervous system exerts significant influence over cardiac function as part of the normal physiological response that allows our bodies to adapt to conditions such as stress and exercise. However, the reaction of the heart to autonomic stimulation is significantly altered in many disease states. In fact, under such conditions, changes in autonomic tone can actually lead to the development of life threatening arrhythmias, or abnormalities in electrical activity, resulting in sudden cardiac death. So what is happening to alter the normally beneficial responses associated with autonomic stimulation? In the heart, many of the acute functional responses to autonomic stimulation involve sympathetic and parasympathetic neurotransmitters acting on receptors that affect the production of cAMP, a second messenger that regulates many aspects of the electrical and mechanical properties of individual cardiac myocytes. We have identified several novel signaling mechanisms that can alter cAMP-dependent responses. We have also demonstrated that subcellular compartmentation of cAMP plays a critical role in determining the magnitude and time course of cAMP-dependent responses. To determine what role such factors play in generating normal as well as abnormal autonomic responses, we use a combination of approaches involving: 1) single cell electrophysiology, 2) molecular biology, 3) biochemistry, 4) transgenic animal models, 5) live cell, fluorescence resonance energy transfer (FRET) imaging, and 6) computational modeling.
Other Lab Members
Shailesh Agarwal, Ph.D.
Warrier, S, A.E. Belevych, M. Ruse, R.L. Eckert, M. Zaccolo, T. Pozzan, and R.D. Harvey. Beta-adrenergic and muscarinic receptor induced changes in cAMP activity in adult cardiac myocytes detected using a FRET-based biosensor. American Journal of Physiology, 289:C455-C461, 2005.
Lehnart, S.E., X.H. Wehrens, S. Reiken. S. Warrier, A.E. Belevych, R.D. Harvey, W. Richter, S.-L. Jin, M. Conti, and A.R. Marks. Phosphodiesterase 4D deficiency in the ryanodine receptor complex promotes heart failure and arrhythmias. Cell 123:1-11, 2005.
Warrier, S., G. Ramamurthy, R.L. Eckert, V.O. Nikolaev, M.J. Lohse, and R.D. Harvey. cAMP microdomains and Ca2+ channel regulation in cardiac ventricular myocytes. Journal of Physiology 580:765-776, 2007.
Iancu, R.V., S.W. Jones, and R.D. Harvey. Compartmentation of cAMP signaling in cardiac myocytes: a computational study. Biophysical Journal 92:3317-3331, 2007.
Iancu, R.V., G. Ramamurthy, S. Warrier, V.O. Nikolaev, M.J. Lohse, S.W. Jones, and R.D. Harvey. Cytoplasmic cAMP concentrations in intact cardiac myocytes. American Journal of Physiology 295:C414-C422, 2008.
Faculty by research area
- Mastick, C
- Mastick C.
- Mastick G.
- Van der Linden
- von Bartheld
- von Bartheld