Genomes and Genes
Affiliation: Novartis Institutes for BioMedical Research
- Participation of Rip2 in lipopolysaccharide signaling is independent of its kinase activityChafen Lu
Millennium Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
J Biol Chem 280:16278-83. 2005..These results demonstrate that Rip2-mediated LPS signaling is independent of its kinase activity. Our findings strongly suggest that Rip2 functions as an adaptor molecule in transducing signals from immune receptors...
- Nucleotide binding to CARD12 and its role in CARD12-mediated caspase-1 activationChafen Lu
Millennium Pharmaceuticals, Inc, 35 Landsdowne Street, Cambridge, MA 02139, USA
Biochem Biophys Res Commun 331:1114-9. 2005..Thus, CARD12 function is dependent on the nucleotide-binding site. Our data provide insights into the molecular mechanisms of CARD12-mediated caspase-1 activation...
- Validating cancer drug targetsJohn D Benson
Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
Nature 441:451-6. 2006..Although the outcome of validation studies can guide cancer research programmes, strictly defined universal validation criteria have not been established...
- Identification of a regulatory autophosphorylation site in the serine-threonine kinase RIP2Marion Dorsch
Millennium Pharmaceuticals, Inc, 35 Landsdowne St, Cambridge, MA 02130, USA
Cell Signal 18:2223-9. 2006..In summary, our results indicate that S176 is a regulatory autophosphorylation site for RIP2 and that S176 phosphorylation can be used to monitor the activation state of RIP2...
- Regulation of IRAK-4 kinase activity via autophosphorylation within its activation loopHong Cheng
Department of Inflammation, Millennium Pharmaceuticals, Inc, Cambridge, MA 02139, USA
Biochem Biophys Res Commun 352:609-16. 2007..The present data indicate that the kinase activity of IRAK-4 is dependent on the autophosphorylations at T342, T345, and S346 in the activation loop...
- The Polycomb group protein Bmi-1 is essential for the growth of multiple myeloma cellsZainab Jagani
Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA
Cancer Res 70:5528-38. 2010..Therefore, these studies not only highlight Bmi-1 as a cancer-dependent factor in multiple myeloma, but also elucidate a novel antiapoptotic mechanism for Bmi-1 function involving the suppression of Bim...
- Mice deficient in PKC theta demonstrate impaired in vivo T cell activation and protection from T cell-mediated inflammatory diseasesKaren Anderson
Inflammation Department, Millennium Pharmaceuticals Inc, 40 Landsdowne St, Cambridge, MA 02139, USA
Autoimmunity 39:469-78. 2006..A fundamental role for PKC theta in T cell activation and in the development of T cell-mediated inflammatory diseases is indicated by these results...
- 1-amino-4-benzylphthalazines as orally bioavailable smoothened antagonists with antitumor activityKaren Miller-Moslin
Department of Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 01239, USA
J Med Chem 52:3954-68. 2009..This compound displayed a good pharmacokinetic profile and also afforded tumor regression in a genetic mouse model of medulloblastoma...
- Targeted inhibition of mutant IDH2 in leukemia cells induces cellular differentiationFang Wang
Agios Pharmaceuticals, Cambridge, MA 02139 4169, USA
Science 340:622-6. 2013..These data provide proof-of-concept that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer...
- Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastomaSilvia Buonamici
Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA
Sci Transl Med 2:51ra70. 2010..Our findings may be useful in informing treatment strategies for medulloblastoma...
- A small molecule inhibitor of mutant IDH2 rescues cardiomyopathy in a D-2-hydroxyglutaric aciduria type II mouse modelFang Wang
Agios Pharmaceuticals Inc, 88 Sidney Street, Cambridge, MA, 02139 4169, USA
J Inherit Metab Dis 39:807-820. 2016..These findings demonstrate the potential therapeutic benefit of an IDH2R140Q inhibitor in patients with D2HGA type II...
- PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancersSusan Wee
Novartis Institutes for BioMedical Research, Cambridge, MA, USA
Cancer Res 69:4286-93. 2009..Our study provides molecular insights that help explain the heterogeneous response of KRAS mutant cancers to MEK pathway inhibition and presents a strong rationale for the clinical testing of combination MEK and PI3K targeted therapies...
- Hedgehog pathway activation in chronic myeloid leukemiaZainab Jagani
Department of Oncology, Novartis Institutes for BioMedical Research, Cambridge, MA, USA
Cell Cycle 9:3449-56. 2010....
- PK1/EG-VEGF induces monocyte differentiation and activationMarion Dorsch
Millennium Pharmaceuticals Inc, 35 Landsdowne St, Cambridge, MA 02139, USA
J Leukoc Biol 78:426-34. 2005..PK1 induces a distinct monocyte-derived cell population, which is primed for release of proinflammatory cytokines that favor a T helper cell type 1 response...
- Ikkepsilon regulates viral-induced interferon regulatory factor-3 activation via a redox-sensitive pathwayHemalatha Indukuri
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555 0366, USA
Virology 353:155-65. 2006....
- Distinct effects of the soluble versus membrane-bound forms of the notch ligand delta-4 on human CD34+CD38low cell expansion and differentiationMedhi Lahmar
U790 INSERM, Institut Gustave Roussy, University Paris XI, PR1, 94800 Villejuif, France
Stem Cells 26:621-9. 2008..Altogether, these results suggest that part of solD4 activity did not rely upon canonical Notch pathway...