2024
Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation
Trogdon M, Abbott K, Arang N, Lande K, Kaur N, Tong M, Bakhoum M, Gutkind J, Stites E. Systems modeling of oncogenic G-protein and GPCR signaling reveals unexpected differences in downstream pathway activation. Npj Systems Biology And Applications 2024, 10: 75. PMID: 39013872, PMCID: PMC11252164, DOI: 10.1038/s41540-024-00400-1.Peer-Reviewed Original ResearchConceptsSignaling networksMathematical models of biochemical reaction networksModels of biochemical reaction networksG-proteinCell signaling networksDisease-causing mutationsComputational systems biologyBiochemical reaction networksDownstream pathway activationSignaling phenotypeSystems biologyBioinformatics analysisGPCR signalingMutationsCo-occurring mutationsOncogenic mutationsPathway activationDiscovery toolPathwayReaction networkSignalCYSLTR2 mutationsDiscoveryPhenotypeMutually-exclusive
2023
Computational Random Mutagenesis to Investigate RAS Mutant Signaling
Stites E. Computational Random Mutagenesis to Investigate RAS Mutant Signaling. Methods In Molecular Biology 2023, 2634: 329-335. PMID: 37074586, PMCID: PMC10530643, DOI: 10.1007/978-1-0716-3008-2_15.Peer-Reviewed Original Research
2015
Use of Mechanistic Models to Integrate and Analyze Multiple Proteomic Datasets
Stites E, Aziz M, Creamer M, Von Hoff D, Posner R, Hlavacek W. Use of Mechanistic Models to Integrate and Analyze Multiple Proteomic Datasets. Biophysical Journal 2015, 108: 1819-1829. PMID: 25863072, PMCID: PMC4390817, DOI: 10.1016/j.bpj.2015.02.030.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorExperimentally detected interactionsPhosphotyrosine-binding domainSrc homology 2Recruitment of proteinsCell line-specific modelsProtein copy numbersProtein-protein interactionsCell signaling networksEpidermal growth factor receptor signalingCell linesWell-characterized roleCell line-specific differencesLow-affinity interactionsLine-specific differencesActivation of EGFR signalingMultiple cell linesLigand-stimulated activationAutophosphorylation sitesSignaling networksProteomic datasetsCopy numberHomolog 2EGFR signalingMap interactionsCooperation between Noncanonical Ras Network Mutations
Stites E, Trampont P, Haney L, Walk S, Ravichandran K. Cooperation between Noncanonical Ras Network Mutations. Cell Reports 2015, 10: 307-316. PMID: 25600866, PMCID: PMC4503519, DOI: 10.1016/j.celrep.2014.12.035.Peer-Reviewed Original ResearchCollection of mutationsRAS pathway mutationsRas signaling networkGenomic data setsPathway mutationsTumor suppressor gene NF1Combinations of mutationsRandom mutagenesisRas mutantsNetwork genesSignaling networksGene NF1Genomic instabilityCancer phenotypeNF1 mutationsMutationsPromote cancerRasMutated cancersIncreased co-occurrenceMutantsMutagenesisGenesPhenotypeNF1
2014
Abstract PR04: Cooperation between Ras network mutations in cancer
Stites E, Trampont P, Haney L, Walk S, Ravichandran K. Abstract PR04: Cooperation between Ras network mutations in cancer. Molecular Cancer Research 2014, 12: pr04-pr04. DOI: 10.1158/1557-3125.rasonc14-pr04.Peer-Reviewed Original ResearchRas signaling networkSignaling networksGenomic dataRAS pathway mutationsRas mutantsNetwork mutationGenomic data setsCancer Cell Line EncyclopediaCancer genome sequencingPathway mutationsTumor suppressor gene NF1Wild-type cellsCancer genomic dataGenome sequenceTumor suppressor gene mutationsCancer Genome AtlasGene NF1Cell-based experimentsDisplay synergyMutational pathwaysRAS networkRas oncogeneCo-occurrenceMutationsRas
2012
Specification, annotation, visualization and simulation of a large rule-based model for ERBB receptor signaling
Creamer M, Stites E, Aziz M, Cahill J, Tan C, Berens M, Han H, Bussey K, Von Hoff D, Hlavacek W, Posner R. Specification, annotation, visualization and simulation of a large rule-based model for ERBB receptor signaling. BMC Systems Biology 2012, 6: 107. PMID: 22913808, PMCID: PMC3485121, DOI: 10.1186/1752-0509-6-107.Peer-Reviewed Original ResearchConceptsCell signaling networksSignaling networksErbB receptor signalingRule-based modeling approachSignaling proteinsPost-translational modification stateSites of post-translational modificationsNetwork-free simulationCellular signaling networksProtein-protein interactionsPost-translational modificationsReceptor signalingSite of modificationActivation of ERKModification statesProtein complexesProtein interactionsContact mapsCellular signalingTyrosine residuesIndividual serinesDevelopment of softwareProteinRule-based modelKinetics of molecular interactionsMathematical Investigation of How Oncogenic Ras Mutants Promote Ras Signaling
Stites E, Ravichandran K. Mathematical Investigation of How Oncogenic Ras Mutants Promote Ras Signaling. Methods In Molecular Biology 2012, 880: 69-85. PMID: 23361982, DOI: 10.1007/978-1-61779-833-7_5.Peer-Reviewed Original Research
2011
Mechanistic modeling to investigate signaling by oncogenic Ras mutants
Stites E, Ravichandran K. Mechanistic modeling to investigate signaling by oncogenic Ras mutants. WIREs Mechanisms Of Disease 2011, 4: 117-127. PMID: 21766467, DOI: 10.1002/wsbm.156.Peer-Reviewed Original ResearchConceptsCell signaling networksSignaling networksCancer phenotypeMutant Ras signalingAcquisition of mutationsRas signalingCell signalingBiochemistry of proteinsLevel of signalMutated genesExpression levelsBiochemical reaction mechanismsPhenotypeMechanistic modelInvestigated signalSignalGenesMutationsRasProteinCancerIndividual reactionsExpression
2010
Modeling Membrane Localization: Case Study of a Ras Signaling Model
Stites E. Modeling Membrane Localization: Case Study of a Ras Signaling Model. Advances In Experimental Medicine And Biology 2010, 680: 661-667. PMID: 20865552, DOI: 10.1007/978-1-4419-5913-3_73.Peer-Reviewed Original Research