Amy Stiegler, PhD
Research Scientist in PharmacologyDownloadHi-Res Photo
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Pharmacology
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Research Scientist in Pharmacology
Appointments
Education & Training
- PhD
- New York University School of Medicine (2007)
- BS
- Georgetown University (2001)
Research
Research at a Glance
Yale Co-Authors
Frequent collaborators of Amy Stiegler's published research.
Publications Timeline
A big-picture view of Amy Stiegler's research output by year.
Alessandro Santin, MD
Gloria Huang, MD, FACOG
Masoud Azodi, MD
Natalia Buza, MD
Pei Hui, PhD, MD
Peter Schwartz, MD
10Publications
205Citations
Publications
2022
SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP
Chau JE, Vish KJ, Boggon TJ, Stiegler AL. SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP. Nature Communications 2022, 13: 4788. PMID: 35970859, PMCID: PMC9378701, DOI: 10.1038/s41467-022-32541-4.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsRhoGAP activitySH3 domainCatalytic arginine fingerIntrinsic GTPase activityRho family GTPasesLiver cancer 1GAP proteinsRhoGAP proteinArginine fingerCo-crystal structureRas GTPasesGAP activityRho proteinsCellular processesGTPase activityMolecular basisKey regulatorTumor suppressorP120RasGAPCell migrationProteinGTPasesRhoGAPCancer 1Binding sites
2021
Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients
Le Coz C, Nguyen DN, Su C, Nolan BE, Albrecht AV, Xhani S, Sun D, Demaree B, Pillarisetti P, Khanna C, Wright F, Chen PA, Yoon S, Stiegler AL, Maurer K, Garifallou JP, Rymaszewski A, Kroft SH, Olson TS, Seif AE, Wertheim G, Grant SFA, Vo LT, Puck JM, Sullivan KE, Routes JM, Zakharova V, Shcherbina A, Mukhina A, Rudy NL, Hurst ACE, Atkinson TP, Boggon TJ, Hakonarson H, Abate AR, Hajjar J, Nicholas SK, Lupski JR, Verbsky J, Chinn IK, Gonzalez MV, Wells AD, Marson A, Poon GMK, Romberg N. Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. Journal Of Experimental Medicine 2021, 218: e20201750. PMID: 33951726, PMCID: PMC8105723, DOI: 10.1084/jem.20201750.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAdolescentAdultAgammaglobulinemiaB-LymphocytesCell DifferentiationCell LineChildChild, PreschoolChromatinDendritic CellsFemaleGene Expression Regulation, DevelopmentalHEK293 CellsHematopoiesisHematopoietic Stem CellsHumansInfantLymphopoiesisMaleMutationPrecursor Cells, B-LymphoidProto-Oncogene ProteinsStem CellsTrans-ActivatorsYoung AdultConceptsPioneer transcription factor PUPro-B cell lineHematopoietic cell fatePre-B cell transitionTranscription factor PUGene expression patternsHuman hematopoietic stemB cell developmentMyeloid cell differentiationBinds target DNAChromatin accessibilityDose-dependent roleCell fateGenomic sitesExpression patternsCell transitionCell developmentCell differentiationHematopoietic stemProgenitor cellsB cellsCell linesAgammaglobulinemia patientsMutationsTarget DNA
2020
The pseudoGTPase group of pseudoenzymes
Stiegler AL, Boggon TJ. The pseudoGTPase group of pseudoenzymes. The FEBS Journal 2020, 287: 4232-4245. PMID: 32893973, PMCID: PMC7544640, DOI: 10.1111/febs.15554.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSignal transductionAmino acid divergenceEnzymatic activityLeucine-rich repeat kinase 2Amino acid differencesP190RhoGAP proteinsRepeat kinase 2Membrane traffickingCellular rolesEnzyme foldImportant mechanistic componentSmall GTPasesTranscriptional controlCellular functionsGTPasesKinase 2PseudoenzymesAcid differencesEC numbersCell migrationFunctional roleMitochondrial activityProteinCargo transportMechanistic componentsThe GTPase-activating protein p120RasGAP has an evolutionarily conserved “FLVR-unique” SH2 domain
Jaber Chehayeb R, Wang J, Stiegler AL, Boggon TJ. The GTPase-activating protein p120RasGAP has an evolutionarily conserved “FLVR-unique” SH2 domain. Journal Of Biological Chemistry 2020, 295: 10511-10521. PMID: 32540970, PMCID: PMC7397115, DOI: 10.1074/jbc.ra120.013976.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsC-terminal SH2 domainSH2 domainFLVR motifSrc homology 2 domainArginine residuesSalt bridgePhosphotyrosine motifsPeptide-bound formsPhosphopeptide bindingUnrecognized diversityDirect salt bridgeIntramolecular salt bridgeIsothermal titration calorimetryPhosphotyrosineP120RasGAPMotifX-ray crystal structureTitration calorimetryAspartic acidTandem substitutionsResiduesBindingDomainGTPaseP190RhoGAPCorrection: Crystal structures of p120RasGAP N-terminal SH2 domain in its apo form and in complex with a p190RhoGAP phosphotyrosine peptide
Jaber Chehayeb R, Stiegler AL, Boggon TJ. Correction: Crystal structures of p120RasGAP N-terminal SH2 domain in its apo form and in complex with a p190RhoGAP phosphotyrosine peptide. PLOS ONE 2020, 15: e0229627. PMID: 32078652, PMCID: PMC7032684, DOI: 10.1371/journal.pone.0229627.Peer-Reviewed Original ResearchCitations
2019
Crystal structures of p120RasGAP N-terminal SH2 domain in its apo form and in complex with a p190RhoGAP phosphotyrosine peptide
Chehayeb R, Stiegler AL, Boggon TJ. Crystal structures of p120RasGAP N-terminal SH2 domain in its apo form and in complex with a p190RhoGAP phosphotyrosine peptide. PLOS ONE 2019, 14: e0226113. PMID: 31891593, PMCID: PMC6938330, DOI: 10.1371/journal.pone.0226113.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsN-terminal SH2 domainSH2 domainPhosphotyrosine peptidesNative gel shiftSite-directed mutagenesisGAP proteinsCo-crystal structurePhosphorylated tyrosineRas pathwayUnliganded formApo formCross-talk occursGel shiftP120RasGAPIsothermal titration calorimetryP190RhoGAPCell growthSpecific conformationCell proliferationProteinX-ray crystal structureTitration calorimetryDisease pathogenesisCrystal structureRhoWhole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patientsMutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy
Brodehl A, Rezazadeh S, Williams T, Munsie NM, Liedtke D, Oh T, Ferrier R, Shen Y, Jones SJM, Stiegler AL, Boggon TJ, Duff HJ, Friedman JM, Gibson WT, Consortium F, Childs SJ, Gerull B. Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy. Translational Research 2019, 208: 15-29. PMID: 30802431, PMCID: PMC7412573, DOI: 10.1016/j.trsl.2019.02.004.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIntegrin-linked kinase geneFirst LIM domainIntegrin-linked kinaseLIM domainsActin cytoskeletonRat myoblast cellsZebrafish showKinase geneCytoplasmic localizationDisease genesArrhythmogenic cardiomyopathyLife-threatening ventricular arrhythmiasMyoblast cellsJunctional proteinsHuman variantsILKSudden cardiac deathGenesFibro-fatty replacementNormal cardiac functionHalf of casesFunctional evidenceHeart muscle disorderMissense variantsDe novo
2018
PseudoGTPase domains in p190RhoGAP proteins: a mini-review.
Stiegler AL, Boggon TJ. PseudoGTPase domains in p190RhoGAP proteins: a mini-review. Biochemical Society Transactions 2018, 46: 1713-1720. PMID: 30514771, PMCID: PMC6501215, DOI: 10.1042/bst20180481.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsP190RhoGAP proteinsDetectable catalytic activityAbundant GTPaseSmall GTPasesRho familyStructural biologyCatalytic cleftEnzyme classesNew family membersFamily membersNoncanonical residuesGTPase enzymeKey regulatorCell migrationOverall proteinProteinBiochemical analysisGTPaseRecent discoveryRecent studiesDomainPseudoenzymesGTPasesCytokinesisDiscoveryThe N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase
Stiegler AL, Boggon TJ. The N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase. Structure 2018, 26: 1451-1461.e4. PMID: 30174148, PMCID: PMC6249675, DOI: 10.1016/j.str.2018.07.015.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsP190RhoGAP proteinsN-terminal GTPase domainProtein-protein interaction domainsNucleotide exchange factorsCanonical GTPaseGTPase domainKnown proteinsEffector proteinsExchange factorInteraction domainNucleotide bindingMutational analysisCritical regulatorGTP-MgGTPProteinBiochemical analysisImportant groupBindingDomainPseudoenzymesGTPase
Academic Achievements & Community Involvement
activity Nature Communications
Journal ServiceReviewerDetails09/21/2020 - Presentactivity Georgetown University Alumni Admissions Program
Public ServiceAlumnus InterviewerDetailsInterview local applicants for admission to Georgetown University2008 - 2020activity CrystalCon
Public ServiceExpert Panel MemberDetailsCareer Panelist, CrystalCon: Lecture and Hands-on Crystal Demonstrations2016 - 2016