Scott Earley
Contact Information
Dr. Scott Earley, Ph.D.
Professor of Pharmacology
Director, Center for Molecular & Cellular Signaling in the Cardiovascular System
1664 N. Virginia Street
Manville Health Sciences Building Room 8
University of Nevada, Reno School of Medicine
Reno, Nevada, USA 89557
searley@med.unr.edu
(775) 784-4117
PubMed: https://pubmed.ncbi.nlm.nih.gov/?term=Earley+S&sort=pubdate
Google Scholar: https://scholar.google.com/citations?user=lR-xaZcAAAAJ&hl=en
ORCID: https://orcid.org/0000-0001-9560-2941
Research Interests
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 chemical agonists. My research team is focused on the concept that TRP channels act as fundamental cellular sensors of the brain’s internal environment and provide critical input for homeostasis, adaptability, and dynamic regulation of the cerebral microvasculature. We have consistently developed and employed innovative experimental approaches, including pioneering studies using total internal reflection fluorescence (TIRF) microscopy to optically record single-channel activity as TRPA1, TRPV3, and TRPV4 sparklets and the application of superresolution microscopy to elucidate the nanoscale architecture of signaling complexes in native smooth muscle cells. These and other methodologies have allowed my research team to discover important roles for TRPM4, TRPV4, and TRPML1 channels in the regulation of smooth muscle cell contractility and to reveal sensory functions of TRPV3 and TRPA1 channels in the cerebral endothelium under pathological conditions.
In addition to our fundamental work on TRP channels, my team has developed an exciting translational collaboration with investigators at UCSF. This research is focused on cerebral small vessel diseases (cSVDs), a group of genetic and idiopathic conditions that injure arterioles, capillaries, and venules in the brain. cSVDs are a leading cause of vascular dementia and contribute to cognitive decline in at least 50% of Alzheimer’s disease patients. The goal of our research is to prevent, delay, or resolve dementia by repairing cerebral vascular control processes that are impaired by cSVDs. Interestingly, we recently reported that impaired TRPM4 channel activity contributes to cSVD in a mouse model of Gould syndrome, a disease caused by autosomal dominant mutations in the gene encoding a specific type of collagen.
Education
Ph.D., Biomedical Sciences, University of New Mexico School of Medicine, 2002
Dissertation: Endothelium-Dependent Vascular Smooth Muscle Cell Hyperpolarization Following Chronic Hypoxia
Mentor: Benjimen R. Walker, Ph.D.
M.S., Microbiology, University of Maine, 1988
Thesis: Cloning and Expression of Genes Encoding Components of the High-Affinity Iron-Uptake System of Vibrio anguillarum 775
Mentor: John T. Singer, Ph.D.
B.S., Electrical Engineering, University of Maine, 1986
Selected Publications
- Yamasaki, E., S. Ali, A. Sanchez Solano, P. Thakore, M. Smith, X. Wang, C. Labelle-Dumais, D. B. Gould, and S. Earley. Faulty TRPM4 channels underlie age-dependent cerebral vascular dysfunction in Gould syndrome Natl. Acad. Sci. USA, 2023 Jan 31;120(5):e2217327120.
- Krishnan, V., S. Ali, A. L. Gonzales, C. S. Griffin, P. Thakore, E. Yamasaki, M. G. Alvarado, M. Johnson, M. Trebak, and S. Earley. STIM1-Dependent Peripheral Coupling Governs the Contractility of Vascular Smooth Muscle Cells. eLife, 2022;11:e70278.
- Ali, S. A. Sanchez Solano, A. L. Gonzales, P. Thakore, V. Krishnan, E. Yamasaki, and S. Earley. Nitric Oxide Signals Through IRAG to Inhibit TRPM4 Channels and Dilate Cerebral Arteries. Function, 2021 Oct 9;2(6).
- Thakore, P., G. Alvarado, S. Ali, A. Mughal, P.W. Pires, E. Yamasaki, H. A. T. Pritchard, B. Isakson, C. Ha Tran, and S. Earley. Brain Endothelial Cell TRPA1 Channels Initiate Neurovascular Coupling. eLife 2021;10:e63040.
- Griffin, C.S., M.G. Alvarado, E. Yamasaki, B.T. Drumm, S. Ali, E.M. Nagle, K.M. Sanders, and S. Earley. The Intracellular Ca2+Release Channel TRPML1 Regulates Lower Urinary Tract Smooth Muscle Contractility. Natl. Acad. Sci. USA, 2020, Dec 1;117(48):30775-30786.
- Thakore, P., H. A. T. Pritchard, C. S. Griffin, E. Yamasaki, B. T. Drumm, C. Lane, K. M. Sanders, Y. Feng Earley, and Earley. TRPML1 Channels Initiate Ca2+ Sparks in Vascular Smooth Muscle Cells. Sci. Signaling, 13 (637), eaba1015, 23 June 2020.