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 ResearchMeSH KeywordsGTP-Binding ProteinsHumansMelanomaModels, BiologicalMutationReceptors, G-Protein-CoupledSignal TransductionSystems BiologyUveal NeoplasmsConceptsSignaling 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
Theoretical analysis reveals a role for RAF conformational autoinhibition in paradoxical activation
Mendiratta G, Stites E. Theoretical analysis reveals a role for RAF conformational autoinhibition in paradoxical activation. ELife 2023, 12: e82739. PMID: 37823369, PMCID: PMC10627510, DOI: 10.7554/elife.82739.Peer-Reviewed Original ResearchComputational 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
2019
A systems mechanism for KRAS mutant allele–specific responses to targeted therapy
McFall T, Diedrich J, Mengistu M, Littlechild S, Paskvan K, Sisk-Hackworth L, Moresco J, Shaw A, Stites E. A systems mechanism for KRAS mutant allele–specific responses to targeted therapy. Science Signaling 2019, 12 PMID: 31551296, PMCID: PMC6864030, DOI: 10.1126/scisignal.aaw8288.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorWild-type Ras activationColorectal cancerSensitivity to EGFR inhibitionEpidermal growth factor receptor inhibitionKRAS mutantEGFR-independent mannerAllele-specific responsesRas activationGrowth factor receptorTumor suppressor neurofibrominPatient tumorsAntibody cetuximabTargeted therapyMechanisms of EGFR signalingCRC patientsEGFR inhibitionCancer treatment decisionsRAS mutationsFactor receptorKRASTherapeutic strategiesTreatment decisionsEGFR signalingPatientsModeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor
Erickson KE, Rukhlenko OS, Shahinuzzaman M, Slavkova KP, Lin YT, Suderman R, Stites EC, Anghel M, Posner RG, Barua D, Kholodenko BN, Hlavacek WS. Modeling cell line-specific recruitment of signaling proteins to the insulin-like growth factor 1 receptor. PLOS Computational Biology 2019, 15: e1006706. PMID: 30653502, PMCID: PMC6353226, DOI: 10.1371/journal.pcbi.1006706.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesSrc homology 2Autophosphorylation sitesInsulin-like growth factor 1 receptorGrowth factor 1 receptorFactor 1 receptorPTB domain-containing proteinsCopy numberDomain-containing proteinsPhosphotyrosine-binding (PTB) domainProtein copy numbersMultiple autophosphorylation sitesProtein abundance profilesMultiple signaling proteinsShort linear motifsOutcome of competitionCell line-specific modelsHomology 2Cytoplasmic domainSignaling proteinsLinear motifsTyrosine kinaseEffects of competitionRule-based modeling approachRelative abundance
2018
Proceedings of the fifth international RASopathies symposium: When development and cancer intersect
Rauen K, Schoyer L, Schill L, Stronach B, Albeck J, Andresen B, Cavé H, Ellis M, Fruchtman S, Gelb B, Gibson C, Gripp K, Hefner E, Huang W, Itkin M, Kerr B, Linardic C, McMahon M, Oberlander B, Perlstein E, Ratner N, Rogers L, Schenck A, Shankar S, Shvartsman S, Stevenson D, Stites E, Stork P, Sun C, Therrien M, Ullian E, Widemann B, Yeh E, Zampino G, Zenker M, Timmer W, McCormick F. Proceedings of the fifth international RASopathies symposium: When development and cancer intersect. American Journal Of Medical Genetics Part A 2018, 176: 2924-2929. PMID: 30302932, PMCID: PMC6312476, DOI: 10.1002/ajmg.a.40632.Peer-Reviewed Original Research
2013
Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine
Stites E. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine. Physical Biology 2013, 10: 026004. PMID: 23406820, DOI: 10.1088/1478-3975/10/2/026004.Peer-Reviewed Original Research
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 ResearchMeSH KeywordsComputational BiologyComputer GraphicsModels, BiologicalReceptor Protein-Tyrosine KinasesSignal TransductionConceptsCell 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 interactions
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 ResearchMeSH KeywordsCell CommunicationHumansModels, GeneticMutationNeoplasmsOncogenesRas ProteinsSignal TransductionConceptsCell signaling networksSignaling networksCancer phenotypeMutant Ras signalingAcquisition of mutationsRas signalingCell signalingBiochemistry of proteinsLevel of signalMutated genesExpression levelsBiochemical reaction mechanismsPhenotypeMechanistic modelInvestigated signalSignalGenesMutationsRasProteinCancerIndividual reactionsExpression
2009
A Systems Perspective of Ras Signaling in Cancer
Stites E, Ravichandran K. A Systems Perspective of Ras Signaling in Cancer. Clinical Cancer Research 2009, 15: 1510-1513. PMID: 19208795, DOI: 10.1158/1078-0432.ccr-08-2753.Peer-Reviewed Original Research
2007
Network Analysis of Oncogenic Ras Activation in Cancer
Stites E, Trampont P, Ma Z, Ravichandran K. Network Analysis of Oncogenic Ras Activation in Cancer. Science 2007, 318: 463-467. PMID: 17947584, DOI: 10.1126/science.1144642.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCell LineCell Line, TumorCell Transformation, NeoplasticComputer SimulationExtracellular Signal-Regulated MAP KinasesGenes, rasGTP PhosphohydrolasesGTPase-Activating ProteinsGuanosine DiphosphateGuanosine TriphosphateHumansMathematicsMetabolic Networks and PathwaysModels, BiologicalNeoplasmsPhosphorylationPoint MutationRas ProteinsSignal Transduction