Neuroscience at HIH Home
NINDS Home NIMH Home NICHD Home NIDCD Home NEI Home NIDCR Home NIA Home NIAAA Home NIDA Home NHGRI Home NIEHS Home NCI Home
National Institutes of Health - Neuroscience at HIH Link to NIH
Link to About Us
Link to Faculty
Link to Areas of Research
Link to Seminars
Link to Interest Groups
Link to Post-doctoral Openings
Link to Home
 

David L. Armstrong, Ph.D., Senior Investigator

Dr. Armstrong completed his Ph.D. in Neurophysiology at the California Institute of Technology in 1978. His graduate studies in the laboratory of Henry Lester focused on the kinetics of tubocurare action at the frog nerve-muscle synapse. As a postdoctoral fellow at University College, London, and the Salk Institute, Dr. Armstrong studied the role of gap junctions in skeletal muscle development and their regulation by neuromuscular activity. In 1984, he joined Roger Eckert's laboratory in the Biology Department at the University of California, Los Angeles, where he began using rat pituitary cell lines as model systems for patch clamp studies of ion channel regulation by signal transduction pathways. Dr. Armstrong joined the intramural research program within the NIEHS in 1987, where he is currently Head of the Membrane Signaling Group and Chief of the Laboratory of Neurobiology. Dr. Armstrong's laboratory is studying the regulation of voltage-activated calcium and potassium channels by hormone signaling through G proteins, calcium and reversible protein phosphorylation.
Photo of David L. Armstrong, Ph.D., Senior Investigator

Staff:



Research Interests:
We currently have two major research interests. In "Ion channel regulation by signal transduction pathways" we use the patch clamp technique to study how ion channel proteins are regulated by G protein signaling through calcium and reversible protein phosphorylation, particularly Ser/Thr protein phosphatases. This gives us new insights into how proteins are regulated post-translationally and reveals new cytoplasmic signal transduction pathways. For example we have discovered that several of the single nucleotide polymorphisms (SNPs) that are associated with disease alter channel activity by introducing or eliminating phosphorylation sites in the channel protein. We also identified PP5 as a novel effector for the Rac GTPase, which is essential for neuronal development and synaptic plasticity.

In "Thyroid hormone signaling" we are pursuing our previous discovery of a new cytoplasmic signaling mechanism through the phosphatidylinositol 3-kinase (PI3K) for the nuclear thyroid hormone receptor, TRbeta. Like thyroid hormone, PI3K is essential for brain development and the regulation of growth and metabolism. PI3K signaling also regulates gene expression, so we have made a mouse strain with a mutant TRb receptor that cannot stimulate PI3K, and we are investigating which of the essential effects of thyroid hormone on brain development and plasticity are mediated by PI3K signaling.

Thus, many of the pathways that we have discovered by studying ion channels are also essential for the healthy development and aging of the brain. Ion channel dysregulation also causes many serious human disorders. Therefore, we have begun to develop high throughput testing of other G protein initiated signaling pathways in the brain that might be disrupted by environmental toxicants.


Selected Recent Publications:
  • Armstrong, D.L., Erxleben, C. & White, J.A. (2010) Patch Clamp Methods for Studying Calcium Channels, Methods in Cell Biology 99, 183-198.

  • Sanchez-Ortiz, E. et al., (2009) Protein phosphatase 5 protects neurons against amyloid-beta toxicity, J. Neurochem. 111, 391-402.

  • Gentile, S. et al., (2008) The human ERG1 channel polymorphism, K897T, creates a phosphorylation site that inhibits channel activity, Proc. Natl. Acad. Sci. USA 105, 14704-8.

  • Armstrong, D.L. (2007) Implications of thyroid hormone signaling through the phosphoinositide 3-kinase for xenobiotic disruption of human health, Endocrine Disrupting Chemicals A. Gore, ed., 193-202.

  • Erxleben, C. et al (2006) Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices, Proc Natl Acad Sci USA 103, 3932-3937.

  • Storey, N. M. et al. (2006) Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone, Proc Natl Acad Sci USA 103, 5197-5201.

  • Gentile et al (2006) Rac GTPase signaling through the PP5 protein phosphatase, Proc natl Acad Sci USA 103, 5202-5206.

All Selected Publications


Contact Information:

Dr. David L. Armstrong
Membrane Signaling Section
Laboratory of Neurobiology, NIEHS
111 Alexander Drive
Research Triangle Park, NC 27709-

Telephone: (919) 541-0062 (office), (919) 541-0062 (laboratory),
Email: armstro3@niehs.nih.gov

top

Home   |   Email List   |   Search   |   Contact Us   |   Privacy Notice   |   Disclaimer   |   Accessibility
Comments or questions about the website?
Send email to neuroscience@nih.gov