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Transmembrane Signaling Group

Molecular Make-up, Physiological Roles & Epigenetic Regulation of Signal Transduction Mechanisms

Lutz Birnbaumer, Ph.D.
Lutz Birnbaumer, Ph.D.
Principal Investigator

Tel (919) 541-3396
Fax (919) 541-0500

Curriculum Vitae (  Download Adobe Reader (60K)
P.O. Box 12233
Mail Drop F1-10
Research Triangle Park, North Carolina 27709
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Full List of Publications (  Download Adobe Reader (247 KB)

Research Summary

Our laboratory has a broad set of interests that include:

  • Molecular mechanism of activation and physiological roles of heterotrimeric G proteins;
  • Molecular makeup, mechanism of activation and physiological roles of the mammalian TRPC channels discovered by us in 1995-1996.
  • Epigentic regulation of gene expression as seen at the GNAS locus and in normal and environmentally insulted mice.

Within the above mentioned areas, we are currently focusing on:

  • describing at the atomic level the interface between a GPCR (rhodopsin) and its cognate G protein (transducin). We use a combination of genetic engineering, purification of recombinant protein and hard core X-ray crystallography. This project, which is just beginning, addresses one of the most important mysteries in the field of signal transduction by G proteins: the molecular mechanism by which the GPCR triggers the exchange of GTP for GDP and the changes that lead from GTP binding to G-alpha subunit activation. GPCRs constitute the largest gene family in the mammalian genome and are targets of innumerable medicines used to control hypertension, migraines, acid secretion in the stomach to name a few. In spite of their importance it is still not known by what molecular mechanism any of the GPCRs activates its cognate G protein.
  • elucidating at the molecular-biochemical level how the interplay between the newly discovered Orai proteins and the TRPC channels forms the so-called Store Operated Calcium Entry (SOCE) channels. We are testing the hypothesis that Orai and TRPCs form obligate heteromeric complexes activated by the store depletion phenomenon. SOCE is a universal phenomenon common to excitable and non-excitable cells. Cellular responses that extend from memory consolidation in neurons to regulation of gene expression in T cells depend on SOCE. Knockout studies have shown that both Orai and TRPCs participate in SOCE, yet the molecular makeup of the SOCE channels remains a mystery. These studies are done in close collaboration with David Armstrong ( who leads the Membrane Signaling Group ( of the Laboratory of Neurobiology (
  • developing methods to evaluate genome wide DNA methylation patterns and to address the unexpected puzzle posed by our finding that expression of the Exon 1-13 encoded Gs-alpha is biallelic, as seen by allele specific RT-PCR, in the face of human and murine clinical phenotypes explained only by mutations in a monoallelicaly expressed (imprinted) Gs-alpha subunit encoded in these same Exons 1-13. Several knock-out and knock-in mice have been created to address this puzzle. To learn more about the imprinting of the locus, the rationale for our hypotheses, and approaches we are following, read our April 2006 Progress Report (  Download Adobe Reader (886 KB) to the NIEHS Board of Scientific Councilors. In developing a method to survey DNA methylation patterns at the genome wide level, we expect to be able to test the hypothesis that environmental exposures may leave a footprint in bone marrow stem cells that can be "read" by analysis of blood cell DNA.
  • physiological roles of G protein alpha subunits and TRPC channels as seen in the living animal are pursued in collaborative studies in which one or more of these genes have been disrupted and/or mutated (classical and conditional knock-out and knock-in mice). One striking phenotype of one of the KO mice, is the rotating behavior of Go-alpha KO mice (

Lutz Birnbaumer, Ph.D., heads the Transmembrane Signaling Group within the Laboratory of Neurobiology. He received his Ph.D. in biochemistry from the University of Buenos Aires in 1966. He has published over 280 peer-reviewed articles in leading biomedical journals, as well as close to 150 reviews and book chapters. Before joining NIEHS in 2001, he served as Chair of Molecular Cell and Developmental Biology at the College of Letters and Science of the University of California, Los Angeles (UCLA). Birnbaumer was Scientific Director of the Division of Intramural Research at NIEHS from October 2001 to February 2007.

For more information about Lutz Birnbaumer, Ph.D., please see his biography (  Download Adobe Reader (75 KB), full list of publications (  Download Adobe Reader (247 KB) and curriculum vitae (  Download Adobe Reader (60 KB).

Research and Training Opportunities

In addition to having opening for two candidates wishing to participate in our studies on the molecular nature of SOCE channels, we have an opening for one more person. It is for a postdoctoral fellow with a strong background in yeast genetics – preferably with the fission yeast S. pombe – to study through second site mutations the Git3p GPCR::Gpa2p G protein interface responsible for the glucose receptor-induced nucleotide exchange at the G protein alpha subunit. Interested candidates should contact Dr. Lutz Birnbaumer at

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Last Reviewed: June 16, 2008