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David L. Armstrong, Ph.D.

Senior Investigator
Neurobiology Laboratory/Membrane Signaling Group
NIEHS
Building 101, Room F207
111 T.W. Alexander Drive
Research Triangle Park, NC 27709
919-541-0062

Research Topics

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, which are the targets of several of the most potent microbial toxins in algal blooms. The patch clamp technique, which can measure each opening and closing transition of individual channel proteins in the surface membrane of intact cells, allows us to ask these questions at the molecular level. This gives us new insights into how proteins are regulated post-translationally and reveals new cytoplasmic signal transduction pathways.

In "Thyroid hormone signaling" we are investigating the signal transduction pathway for the rapid cellular effects of thyroid hormone. Our previous studies of Kv11 regulation in pituitary cells led to the discovery of a new cytoplasmic mechanism linking the nuclear thyroid hormone receptor, TRbeta, to the phosphatidylinositol 3-kinase (PI3K). Like thyroid hormone, PI3K is essential for brain development and the regulation of growth and metabolism. We have shown that TRbeta serves as a hormone-dependent, cytoplasmic scaffold for PI3K and the tyrosine kinases, which stimulate its activity, and we have identified the mechanisms of binding for both partners. PI3K 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.

Biography

Dr. Armstrong completed his Ph.D. in Neurophysiology in 1978 at the California Institute of Technology, where he studied the kinetics of tubocurare action at the frog nerve-muscle synapse with Henry Lester. 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, as Head of the Membrane Signaling Group, which investigates the regulation of voltage-activated calcium and potassium channels by hormone signaling through G proteins, calcium and reversible protein phosphorylation.

Selected Publications

  1. Erxleben C, Liao Y, Gentile S, Chin D, Gomez-Alegria C, Mori Y, Birnbaumer L, Armstrong DL. Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices. Proc Natl Acad Sci U S A. 2006;103(10):3932-7.
  2. Storey NM, Gentile S, Ullah H, Russo A, Muessel M, Erxleben C, Armstrong DL. Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone. Proc Natl Acad Sci U S A. 2006;103(13):5197-201.
  3. Gentile S, Darden T, Erxleben C, Romeo C, Russo A, Martin N, Rossie S, Armstrong DL. Rac GTPase signaling through the PP5 protein phosphatase. Proc Natl Acad Sci U S A. 2006;103(13):5202-6.
  4. Gentile S, Martin N, Scappini E, Williams J, Erxleben C, Armstrong DL. The human ERG1 channel polymorphism, K897T, creates a phosphorylation site that inhibits channel activity. Proc Natl Acad Sci U S A. 2008;105(38):14704-8.
  5. Sanchez-Ortiz E, Hahm BK, Armstrong DL, Rossie S. Protein phosphatase 5 protects neurons against amyloid-beta toxicity. J Neurochem. 2009;111(2):391-402.
This page was last updated on August 20th, 2013