Research Topics
Genomes and Genes | Cristina M RondinoneSummaryAffiliation: F. Hoffmann-La Roche Ltd Publications
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Publications
RNAi: for functional analysis and target validationCristina M Rondinone
Hoffmann La Roche, Department of Metabolic Diseases, 340 Kingsland Street, Nutley, NJ 07110, USA
Expert Opin Ther Targets 10:337-40. 2006..Discussions focused in the design of siRNA for effective gene silencing, RNAi screens to identify new targets, RNAi delivery and the in vivo validation of targets using this technology...
Minireview: ribonucleic acid interference for the identification of new targets for the treatment of metabolic diseasesCristina M Rondinone
Department Metabolic Diseases, Hoffmann La Roche, Nutley, New Jersey 07110, USA
Endocrinology 147:2650-6. 2006..Also reviewed are the in vivo proof of principle experiments that provide the validation of these new targets for the development of RNAi-based therapeutics for diabetes...
Adipocyte-derived hormones, cytokines, and mediatorsCristina M Rondinone
Department Metabolic Diseases, Hoffmann La Roche, Nutley, New Jersey 07110, USA
Endocrine 29:81-90. 2006....
Therapeutic potential of RNAi in metabolic diseasesCristina M Rondinone
Department Metabolic Diseases, Hoffmann La Roche, Nutley, NJ 07110, USA
Biotechniques . 2006....
RNA interference to target lipid disordersCristina M Rondinone
Department Metabolic Diseases, Hoffmann La Roche, Nutley, New Jersey 07110, USA
Curr Opin Lipidol 19:285-8. 2008..This review focuses on proof-of-principle experiments providing validation of new targets for the development of RNA interference-based therapeutics for dyslipidemia...
Diabetes: the latest developments in inhibitors, insulin sensitisers, new drug targets and novel approaches. October 18-19, 2004, The Hatton, London, UKCristina M Rondinone
Abbott Laboratories, Metabolic Disease Research, Dept 47R, AP10, 100 Abbott Park Road, Abbott Park, IL 60064 6099, USA
Expert Opin Ther Targets 9:415-8. 2005..Discussions focused on several emerging therapeutic areas, including novel compound developments and target identification with the use of conventional methods and recently emerged technologies, such as siRNA, genomics and proteomics...
Antisense protein tyrosine phosphatase 1B reverses activation of p38 mitogen-activated protein kinase in liver of ob/ob miceRebecca J Gum
Abbott Laboratories, Department R 4CK, AP10 1, 100 Abbott Park Road, Abbott Park, Illinois 60064 3502, USA
Mol Endocrinol 17:1131-43. 2003..This study demonstrates that reduction of PTP1B protein using ASO reduces activation of p38 and its substrates TNFalpha and CREB in liver of diabetic mice, which correlates with decreased hyperglycemia and hyperinsulinemia...
Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob miceRebecca J Gum
Metabolic Disease Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA
Diabetes 52:21-8. 2003..These results indicate that reduction of PTP1B is sufficient to increase insulin-dependent metabolic signaling and improve insulin sensitivity in a diabetic animal model...
PTP1B antisense-treated mice show regulation of genes involved in lipogenesis in liver and fatJeffrey F Waring
Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 6123, USA
Mol Cell Endocrinol 203:155-68. 2003..In summary, microarray results suggest that reduction of PTP1B may alleviate hyperglycemia and enhance insulin sensitivity by a different mechanism than TZD treatment...
Reduction of protein-tyrosine phosphatase-1B increases insulin signaling in FAO hepatoma cellsJill E Clampit
Insulin Signaling, Metabolic Diseases Research, Global Pharmaceutical Research Division, Abbott Laboratories, Department 47R, Building AP10, 100 Abbott Park Road, Abbott Park, IL 60064 6009, USA
Biochem Biophys Res Commun 300:261-7. 2003..These results demonstrate that reduction of PTP1B can modulate key insulin signaling events downstream of the insulin receptor...
PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic miceBradley A Zinker
Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064 3500, USA
Proc Natl Acad Sci U S A 99:11357-62. 2002..These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes...
Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitorsHongyu Zhao
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
Bioorg Med Chem Lett 14:5543-6. 2004..Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells...
Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitorGang Liu
Metabolic Disease Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6098, USA
J Med Chem 46:4232-5. 2003....
Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor gamma coactivator 1 beta and increases plasma triglyceride despite reduced glucose and insulin levels in diet-induced obese miceRuojing Yang
Department of Metabolic Disease Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA
J Biol Chem 282:22765-74. 2007..Our results demonstrate that liver-specific knockdown of JNK1 lowers circulating glucose and insulin levels but increases triglyceride levels in DIO mice...
Reduction of PTP1B induces differential expression of PI3-kinase (p85alpha) isoformsCristina M Rondinone
Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Biochem Biophys Res Commun 323:652-9. 2004....
Discovery of a new class of 4-anilinopyrimidines as potent c-Jun N-terminal kinase inhibitors: Synthesis and SAR studiesMei Liu
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
Bioorg Med Chem Lett 17:668-72. 2007..SAR studies led to the discovery of potent JNK1 inhibitors with good enzymatic activity as well as cellular potency represented by compound 2b. Kinase selectivity profile and the crystal structure of 2b are also described...
Proteasome inhibitors regulate tyrosine phosphorylation of IRS-1 and insulin signaling in adipocytesCristina M Rondinone
Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Department 47R, Building AP10, 100 Abbott Park Road, 60064, Abbott Park, IL, USA
Biochem Biophys Res Commun 296:1257-63. 2002..quot; In conclusion, proteasome inhibitors can regulate the tyrosine phosphorylation of IRS-1 and the downstream insulin signaling pathway, leading to glucose transport...
Endothelin antagonism improves hepatic insulin sensitivity associated with insulin signaling in Zucker fatty ratsNathalie Berthiaume
Global Pharmaceutical Research and Development Division, Metabolic Disease Research, Abbott Laboratories, Abbott Park, IL 60064-3500, USA
Metabolism 54:1515-23. 2005..These results indicate that therapeutic ET antagonism may assist in correcting the insulin-resistant state...
Mammalian target of rapamycin regulates IRS-1 serine 307 phosphorylationChristian J Carlson
Insulin Signaling, Metabolic Diseases Division, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, IL 60064, USA
Biochem Biophys Res Commun 316:533-9. 2004..Finally, we demonstrated that serine 307 phosphorylated IRS-1 is detected primarily in the cytosolic fraction...
Enhanced basal activation of mitogen-activated protein kinases in adipocytes from type 2 diabetes: potential role of p38 in the downregulation of GLUT4 expressionChristian J Carlson
Insulin Signaling, Metabolic Diseases Division, Global Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, USA
Diabetes 52:634-41. 2003..Furthermore, upregulation of the p38 pathway might contribute to the loss of GLUT4 expression observed in adipose tissue from type 2 diabetic patients...
PKCtheta is a key player in the development of insulin resistanceDeanna Haasch
Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Biochem Biophys Res Commun 343:361-8. 2006..These findings suggest that PKCtheta mediates not only insulin resistance in muscle but also in liver, which may contribute to the development of whole body insulin resistance and diabetes...
Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activityBruce G Szczepankiewicz
Metabolic Disease Research, Global Pharmaceutical Research and Discovery Organization, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064 6098, USA
J Med Chem 49:3563-80. 2006..The new compounds were over 1,000-fold selective for JNK-1 and -2 over other MAP kinases including ERK2, p38alpha, and p38delta and showed little inhibitory activity against a panel of 74 kinases...
Pharmacological inhibition of p38 MAP kinase results in improved glucose uptake in insulin-resistant 3T3-L1 adipocytesChristian J Carlson
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, IL 60064, USA
Metabolism 54:895-901. 2005..These data indicate that p38 inhibition can enhance glucose uptake through regulating the expression of GLUT1 and 4, but did not prevent the development of insulin resistance...
JNK: bridging the insulin signaling and inflammatory pathwayGang Liu
Abbott Laboratories, Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Park, IL 60064, USA
Curr Opin Investig Drugs 6:979-87. 2005..This review highlights recent advances in small-molecule inhibitors of JNK that have also been targeted for other diseases with an inflammatory component such as stroke, rheumatoid arthritis, and Alzheimer's and Parkinson's diseases...
Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesisCristina M Rondinone
Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA
Diabetes 51:2405-11. 2002..These results demonstrate that PTP1B antisense treatment can modulate fat storage and lipogenesis in adipose tissue and might implicate PTP1B in the enlargement of adipocyte energy stores and development of obesity...
The emerging role of the intestine in metabolic diseasesWilliam D Bradley
Metabolic and Vascular Diseases Department, Hoffmann La Roche Inc, Nutley, NJ, USA
Arch Physiol Biochem 117:165-76. 2011....
Genetic association meets RNA interference: large-scale genomic screens for causation and mechanism of complex diseasesMitchell Martin
Roche, Department of Research Informatics, Genetics and Genomics, Nutley, NJ 07110, USA
Pharmacogenomics 8:455-64. 2007..Wider applicability of RNA interference methods will closely follow continued progress on efficient delivery into appropriate cell models and target tissues...
Discovery of orally active carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxamide as potent diacylglycerol acyltransferase-1 inhibitors for the potential treatment of obesity and diabetesYimin Qian
Department of Discovery Chemistry, Hoffmann La Roche Inc, 340 Kingsland Street, Nutley, New Jersey 07110, United States
J Med Chem 54:2433-46. 2011..3, 1, and 3 mg/kg, p.o., qd) during a 21-day efficacy study. Furthermore, compound 29 demonstrated improved glucose tolerance determined by an oral glucose tolerance test (OGTT)...
Selective protein tyrosine phosphatase 1B inhibitors: targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligandsGang Liu
Metabolic Disease Research and Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064 6098, USA
J Med Chem 46:3437-40. 2003....
Rapamycin partially prevents insulin resistance induced by chronic insulin treatmentCathleen E Berg
Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
Biochem Biophys Res Commun 293:1021-7. 2002..These results suggest that chronic insulin exposure leads to a down-regulation of PKB and MAPK pathways through different mechanisms in adipocytes...
Developmental switch from prolonged insulin action to increased insulin sensitivity in protein tyrosine phosphatase 1B-deficient hepatocytesAgueda Gonzalez-Rodriguez
Instituto de Investigaciones Biomédicas Alberto Sols Centro mixto Consejo Superior de Investigaciones Cientificas Universidad Autónoma, c Arturo Duperier 4, 28029 Madrid, Spain
Endocrinology 148:594-608. 2007..Thus, changes in IR and IRS-2 expression and in the balance between regulatory and catalytic subunits of phosphatidylinositol 3-kinase are necessary to achieve insulin sensitization in adult PTP1B(-/-) hepatocytes...
Protein-tyrosine phosphatase 1B-deficient myocytes show increased insulin sensitivity and protection against tumor necrosis factor-alpha-induced insulin resistanceIria Nieto-Vazquez
Department of Biochemistry, Faculty of Pharmacy, Universidad Complutense, 28040 Madrid, Spain
Diabetes 56:404-13. 2007..However, mice lacking PTP1B maintained a rapid clearance of glucose and insulin sensitivity and displayed normal muscle insulin signaling regardless the presence of TNF-alpha...
PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexesAgueda Gonzalez-Rodriguez
Instituto de Investigaciones Biomedicas Alberto Sols, C Arturo Pérez Duperier 4, 28029 Madrid, Spain
Am J Physiol Gastrointest Liver Physiol 295:G338-47. 2008....
