New York Times: June 22, 1993:
Scientists Decipher Mysterious Process of Signaling in Cells.
By Gina Kolata
An article in the Science Section of the New York Times describing the
work done in the Crabtree and Schreiber labs that lead to an understanding
of the Ca2+/calcineurin/NF-AT signaling pathway and the mechanism of action
of cyclosporin A and FK506.....more
New York Times: September 3, 1996
A Molecule that Switches Genes On and Off
by Gina Kolata.
A summary of the development of synthetic ligands or CID’s and
their use to activate and inactivate transcription by David Spencer,
Steffan
Ho and others in the Crabtree and Schreiber labs. Note the shape of the
receptors in the diagram used in the article...more
Discovery Magazine: February 1996:
Conversations in a Cell,
by Gary Taubes
More on the discovery of the mechanism of action of CsA and the development
of synthetic ligands in the Crabtree and Schreiber labs.
Wall Street Journal: January 1999
An article summarizing the successful use of synthetic ligands to activate transcription of EPO in monkeys and mice. The work was done at Ariad in collaboration with Jim Wilson and uses the system for transcriptional activation developed by Steffan Ho (Nature 382, 822 1996)
New York Times, February 23, 1999:
Gene Therapy
Passes Important Tests in Monkeys.
by Nicholas Wade
An article in the
summarizing the use of synthetic ligands for regulated
gene therapy in monkeys
using the system developed by Stephan Ho and Steve Biggar
in the laboratory (Nature 382, 822 1996). The article highlights
the studies
of Jim Wilson
at the
University of Penn and Mike Gilman at Ariad.
BBC News, Oct 29th 2004 pdf
Molecule Offers Alzheimer's Hope
A brief report on Isabella Graef's and Jason Gastwicki's Science paper appearing on the same date and earlier work by Roger Breisiwitz in the lab demonstating a new strategy for making drugs. We call these Trojan Horse molecules because they diffuse into the cell and then bind very tightly to an endogenous protein generating a complex with sufficient steric bulk and surface area to block the continued aggregation of A-beta peptide from Amyloid A protein. Aggregates of these peptides are toxic and hence preventing their aggregation prevents toxicity to neurons. Similar brief reports on this work were published by CNN news, CBS and Scientific American.
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Gestwicki J, Crabtree GR and Graef IA Harnessing Chaperones to Generate Potent Small Molecule Inhibitors of Amyloid Aggregation. Science, in Press Oct 29, 2004 p 865-869, PDF or HTML For information from the popular press see BBC News or Scientific American or CNN News Chang, CP, Neilson, J.R. Bayle, J.H., Gestwicki, J.E., Kuo, a. Stankunas, K. Graef, IA and Crabtree G.R. A Field of Calcineurin-NFAT signaling underlies heart valve morphogenesis, Cell Sept 3rd 2004. Note the cover design and the accompanying editorial. PDF or HTLM for the paper, PDF or HTML for the Editorial Rose RB, Pullen KE, Bayle JH, Crabtree GR, Alber
T.Biochemical and structural basis for partially redundant enzymatic
and transcriptional functions of DCoH and DCoH2. Parsons SA, Millay DP, Wilkins BJ, Bueno OF, Tsika
GL, Neilson JR, Liberatore CM, Yutzey KE, Crabtree GR, Tsika RW,
Molkentin JD. Genetic loss of calcineurin blocks
mechanical overload-induced skeletal muscle fiber type switching
but not hypertrophy. Brand M, Ranish JA, Kummer NT, Hamilton J, Igarashi
K, Francastel C, Chi TH, Crabtree GR, Aebersold R, Groudine M.
Dynamic changes in transcription factor complexes during erythroid
differentiation revealed by quantitative proteomics. Neilson JR, Winslow MM, Hur EM, Crabtree GR. Stankunas et al. Condtional Protein Alleles Using Knock-in Mice and a Chemical Inducer of Dimerization Mol Cell Dec 12, 1615-1624, 2003.HTML PDF Graef I.A. et al Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons.Cell. 2003 May 30;113(5):657-70. HTML PDF Chi et al. Sequential roles of Brg, the ATPase subunit of BAF chormatin remodeling complexes in thymocyte development. Immunity 2003, 169-182 HTML PDF Chang CP, et al. Sonographic staging of the developmental status of mouse embryos in utero.Genesis. 2003 May;36(1):7-11. HTML Olave I, et al Identification of a polymorphic, neuron-specific chromatin remodeling complex.Genes Dev. 2002 Oct 1;16(19):2509-17. HTML PDF Sheridan et al. Protein kinase A negatively modulates the nuclear accumulation of NF-ATc1 by priming for subsequent phosphorylation by glycogen synthase kinase-3.J Biol Chem. 2002 Dec 13;277(50):48664-76 HTML Diehn M, et al .Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11796-801. HTML Chi et al.Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes.Nature. 2002 Jul 11;418(6894):195-9. HTML PDF Bayle et. al. Hyperphenylalaninemia and impaired glucose tolerance in mice lacking the bifunctional DCoH gene.J Biol Chem. 2002 Aug 9;277(32):28884-91HTML Rando OJ, et al. Phosphatidylinositol-dependent actin filament binding by the SWI/SNF-like BAF chromatin remodeling complex.Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2824-9. HTML Graef IA, et al. Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature.Cell. 2001 Jun 29;105(7):863-75 HTML PDF Biggar SR, and Crabtree GR. Cell signaling can direct either binary or graded transcriptional responses.EMBO J. 2001 Jun 15;20(12):3167-76 HTML PDF Graef IA, et al. Evolutionary relationships among Rel domains indicate functional diversification by recombination.Proc Natl Acad Sci U S A. 2001 May 8;98(10):5740-5 HTML Graef IA, et al. L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons.Nature. 1999 Oct 14;401(6754):703-8 HTML PDF |
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Winslow MM, et al. Calcium signalling in lymphocytes.Curr Opin Immunol. 2003 Jun;15(3):299-307. HTML Rando OJ, et al. Second messenger control of chromatin remodeling. Nat Struct Biol. 2003 Feb;10(2):81-3. HTML Olave IA, et al Nuclear actin and actin-related proteins in
chromatin remodeling. Crabtree GR, Olson EN. NFAT signaling: choreographing the social
lives of cells. Graef IA, et al. NFAT signaling in vertebrate development. Curr Opin Genet Dev. 2001 Oct;11(5):505-12 HTML Chi TH, and Crabtree GR. Perspectives: signal transduction. Inositol phosphates in the nucleus.Science. 2002 Mar 17;287(5460):1937-9 HTML Crabtree GR. Calcium, calcineurin, and the control of transcription. Stewart S, Crabtree GR. Transcription. Regulation of the regulators. |
