Summary
My lab is focused on understanding the functional significance of the transient receptor potential (TRP) superfamily of cation channels in the cerebral vasculature and other organ systems. The mammalian TRP superfamily is composed of 28 distinct gene products assigned to six subfamilies based on sequence homology. TRP channels act as fundamental sensors of the environment at the cellular level and mediate appropriate responses to stimuli such as light, pressure, temperature, changes in osmolarity, and certain chemical agonists. Although prominent in sensory neurons, multiple TRP channels are present in most types of cells. We are primarily interested in learning how TRP channels are involved in smooth muscle excitability and contractility, endothelium-dependent vasodilation, and cellular proliferation during pathophysiological conditions. We employ a broad range of modern experimental approaches and techniques. For example, high-speed confocal Ca2+ imaging in conjunction with mice expressing genetically-encoded Ca2+ indicators in the endothelium are used to study transient, localized Ca2+ signaling in intact arteries and isolated cells. Ion channel regulation is studied using both conventional patch clamp electrophysiology and total internal reflection fluorescent microscopy (TIRFM). Tissue-specific gene knockout and delivery of siRNA to intact cerebral arteries are routinely used to disrupt gene expression, and in combination with pressure myography, ratiometric Ca2+ imaging, and intracellular microelectrode electrophysiology, to examine the consequences of protein downregulation on arterial function. Live-cell imaging techniques, including TIRFM and fluorescence recovery after photobleaching (FRAP), are used to study ion channel trafficking. Experiments are typically performed under physiological conditions using intact resistance arteries or acutely isolated cells from these vessels.
Education
- Ph.D., Biomedical Sciences, University of New Mexico School of Medicine, 2002
Selected publications
- Zhao, L. M.N. Sullivan, M. Chase, A.L. Gonzales, and S. Earley. Calcineurin/NFAT-Coupled TRPV4 Ca2+ Sparklets Stimulate Airway Smooth Muscle Cell Proliferation. Am. J. Res. Cell. and Mol. Bio., in press, 2014.
- Kirby B.S., A. Bruhl, M.N. Sullivan, M. Francis, F. A. Dinenno, and S. Earley. Robust Internal Elastic Lamina Fenestration in Skeletal Muscle Arteries PLoS One, 8(1) e54849, 2013.
- Sullivan, M.N., M. Francis, N. L. Pitts, M. S. Taylor and S. Earley. Optical Recording Reveals Novel Properties of GSK1016790AInduced Vanilloid Transient Receptor Potential Channel TRPV4 Activity in Primary Human Endothelial Cells Mol. Pharmacol., 82(3):464-472, 2012.
- Gonzales, A.L. and S. Earley. Endogenous Cytosolic Ca2+ Buffering is Necessary for TRPM4 Activity in Cerebral Artery Smooth Muscle Cells Cell Calcium, 51(1):82-93, 2012.
- Earley, S., A.L. Gonzales, and R. Crnich. Cerebral Artery Dilation Mediated by Endothelial TRPA1 and Ca2+-Activated K+ Channels. Circ Res. 104(8):987-94, 2009.