Robert D. Harvey

Department:                Pharmacology
Academic Unit:           School of Medicine
Title:                            Professor
P rofessional degrees (Degree, year, Institution): Ph.D., 1987, Northwestern

Contact Information

Mail Stop: 220      
Phone: 775-784-4119
Fax: 775-784-1620
e-mail: rdharvey@medicine.nevada.edu

http://www.medicine.nevada.edu/dept/Pharmacology/faculty/harvey.html

Research Area(s)

Biophysics, Cell Biology, Physiology, Pharmacology

Research Interests

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.
Richard Tyser

Selected Publications

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.

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=15788489

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.

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=16213210

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.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2075464&tool=pmcentrez

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.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1852367&tool=pmcentrez

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.

http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=DetailsSearch&term=18550706