2024
Phosphoenolpyruvate carboxykinase-2 (PCK2) is a therapeutic target in triple-negative breast cancer
Gunasekharan V, Lin H, Marczyk M, Rios-Hoyo A, Campos G, Shan N, Ahmed M, Umlauf S, Gareiss P, Raaisa R, Williams R, Cardone R, Siebel S, Kibbey R, Surovtseva Y, Pusztai L. Phosphoenolpyruvate carboxykinase-2 (PCK2) is a therapeutic target in triple-negative breast cancer. Breast Cancer Research And Treatment 2024, 208: 657-671. PMID: 39177932, DOI: 10.1007/s10549-024-07462-z.Peer-Reviewed Original ResearchMetabolic fluxTriple-negative breast cancerReduced metabolic fluxMDA-MB-231 cellsCell growth in vitroEnzyme assays in vitroMDA-MB-231Potential small molecule inhibitorsPyruvate carboxylaseGrowth in vitroSmall molecule inhibitorsIn silico screeningEnzyme assaysAssay in vitroEnzymatic assayCell lines in vitroEnzyme activityGrowth inhibitory activityBT-549Breast cancerIn vitro screeningBreast cell lines in vitroPhosphoenolpyruvateSignificant growth inhibitory activityLines in vitroThe cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis
McCool M, Bryant C, Abriola L, Surovtseva Y, Baserga S. The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis. PLOS Biology 2024, 22: e3002718. PMID: 38976757, PMCID: PMC11257408, DOI: 10.1371/journal.pbio.3002718.Peer-Reviewed Original ResearchRibosome biogenesis factorsRibosome biogenesisBiogenesis factorsCell growthNucleolar functionRegulation of nucleolar functionHuman ribosome biogenesisProtein synthesisProduction of ribosomesFamily of proteinsSource of mutagenesisLevel of protein synthesisCytidine deaminase familyIncreased cell growthPromote cell growthPre-rRNAPotential direct rolePre-mRNATransient overexpressionRibosomeGenomic mutationsBiogenesisMCF10A cellsMaturation stepsAPOBEC3ADiscovery of novel microRNA mimic repressors of ribosome biogenesis
Bryant C, McCool M, González G, Abriola L, Surovtseva Y, Baserga S. Discovery of novel microRNA mimic repressors of ribosome biogenesis. Nucleic Acids Research 2024, 52: 1988-2011. PMID: 38197221, PMCID: PMC10899765, DOI: 10.1093/nar/gkad1235.Peer-Reviewed Original Research
2021
Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure–Activity Relationships and Facilitates Mechanism of Action Studies
Wernke KM, Tirla A, Xue M, Surovtseva YV, Menges FS, Herzon SB. Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure–Activity Relationships and Facilitates Mechanism of Action Studies. Journal Of The American Chemical Society 2021, 143: 15824-15833. PMID: 34524796, DOI: 10.1021/jacs.1c07559.Peer-Reviewed Original ResearchConceptsFanconi anemia DNA repair pathwayBiosynthetic gene clusterDNA repair pathwaysGene clusterRepair pathwaysDNA bindingBacterial phenotypesInduces DNAGenotoxic effectsHuman microbiomeColibactinBiosynthetic precursorNatural product structuresBiological studiesPathwayStructure-activity relationshipsAction studiesGenotoxic metabolitesOrganismsOncogenesisDNATumorigenesisMicrobiomeFacilitate mechanismsPhenotype
2020
854 Functional drug screening identifies candidate synergistic combinations for CTCL therapy
Yumeen S, Mirza F, Lewis J, King A, Kim S, Carlson K, Umlauf S, Surovtseva Y, Foss F, Girardi M. 854 Functional drug screening identifies candidate synergistic combinations for CTCL therapy. Journal Of Investigative Dermatology 2020, 140: s111. DOI: 10.1016/j.jid.2020.03.870.Peer-Reviewed Original ResearchScreening Novel Agent Combinations to Expedite CTCL Therapeutic Development
Mirza FN, Yumeen S, Lewis JM, King ALO, Kim S, Carlson KR, Umlauf S, Surovtseva YV, Foss FM, Girardi M. Screening Novel Agent Combinations to Expedite CTCL Therapeutic Development. Journal Of Investigative Dermatology 2020, 141: 217-221. PMID: 32534802, DOI: 10.1016/j.jid.2020.05.097.Peer-Reviewed Original ResearchJAK inhibition synergistically potentiates BCL2, BET, HDAC, and proteasome inhibition in advanced CTCL
Yumeen S, Mirza FN, Lewis JM, King ALO, Kim SR, Carlson KR, Umlauf SR, Surovtseva YV, Foss FM, Girardi M. JAK inhibition synergistically potentiates BCL2, BET, HDAC, and proteasome inhibition in advanced CTCL. Blood Advances 2020, 4: 2213-2226. PMID: 32437546, PMCID: PMC7252559, DOI: 10.1182/bloodadvances.2020001756.Peer-Reviewed Original ResearchConceptsCutaneous T-cell lymphomaJAK inhibitionCTCL cellsMalignant cutaneous T-cell lymphomasAdvanced cutaneous T-cell lymphomaTreatment of CTCLAvailable systemic treatment optionsSkin-homing T lymphocytesSystemic treatment optionsT-cell lymphomaCTCL cell linesHistone deacetylase inhibitionGeneralized cytotoxic effectExpression of Bcl2Advanced diseaseSuch patientsPeripheral bloodTreatment optionsJAK/STAT pathwayT lymphocytesPreclinical assessmentTherapeutic targetStrong potentiationExtrinsic apoptosis pathwayDeacetylase inhibition
2019
676 Exploring novel therapeutic targets in the treatment of cutaneous T-cell lymphoma
Yumeen S, King A, Kim S, Lewis J, Carlson K, Umlauf S, Surovtseva Y, Foss F, Girardi M. 676 Exploring novel therapeutic targets in the treatment of cutaneous T-cell lymphoma. Journal Of Investigative Dermatology 2019, 139: s116. DOI: 10.1016/j.jid.2019.03.752.Peer-Reviewed Original Research
2018
Model Colibactins Exhibit Human Cell Genotoxicity in the Absence of Host Bacteria
Shine EE, Xue M, Patel JR, Healy AR, Surovtseva YV, Herzon SB, Crawford JM. Model Colibactins Exhibit Human Cell Genotoxicity in the Absence of Host Bacteria. ACS Chemical Biology 2018, 13: 3286-3293. PMID: 30403848, PMCID: PMC7001666, DOI: 10.1021/acschembio.8b00714.Peer-Reviewed Original ResearchConceptsHost bacteriaGenotoxic secondary metabolitesDNA double-strand breaksDNA interstrandSpecific protein domainsWild-type pathwayDouble-strand breaksFull molecular mechanismsCell culturesFamily of metabolitesHuman cell linesProtein domainsPresence of membranesModule skippingCellular phenotypesExtracellular supplementationNative pathwaysHuman cell culturesMolecular mechanismsSecondary metabolitesHuman cellsColibactinEfficient DNA interstrandObserved modulesPhenotypeHigh throughput discovery of novel regulators of human ribosome biogenesis
Baserga S, Farley‐Barnes K, McCann K, Ogawa L, Merkel J, Surovtseva Y. High throughput discovery of novel regulators of human ribosome biogenesis. The FASEB Journal 2018, 32: 526.25-526.25. DOI: 10.1096/fasebj.2018.32.1_supplement.526.25.Peer-Reviewed Original ResearchRibosome biogenesisNucleolar functionNumber of nucleoliMammalian cellsGenome-wide siRNA screenRNA polymerase I transcriptionHuman ribosome biogenesisPre-ribosomal RNAPolymerase I transcriptionExperimental Biology 2018 MeetingHigh-throughput discoveryNucleolar proteinsRibosomal DNAProtein regulatorsI transcriptionNew regulatorNovel regulatorSiRNA screenBiogenesisHuman cellsProteinRegulatorNucleoliFASEB JournalThroughput discovery
2017
DIPG-33. BIOLOGICAL CHARACTERIZATION OF PPM1D MUTATIONS IN THE CONTEXT OF DIPG
Fons N, Sundaram R, Surovtseva Y, Rusin S, Kettenbach A, Breuer G, Bindra R. DIPG-33. BIOLOGICAL CHARACTERIZATION OF PPM1D MUTATIONS IN THE CONTEXT OF DIPG. Neuro-Oncology 2017, 19: iv12-iv12. PMCID: PMC5475004, DOI: 10.1093/neuonc/nox083.048.Peer-Reviewed Original ResearchDNA damage response networkDNA damage response proteinsDamage response proteinsRecent genomic analysesProtein phosphataseFirst cell lineGenomic analysisResponse proteinsMolecular basisKey proteinsDiffuse intrinsic pontine gliomaDiverse arrayMutant astrocytesOncogenic potentialResponse networkBasal activationMutationsTruncating alterationsAlternative roleProtein expressionCell linesBiological characterizationTruncating mutationsPPM1DNovel list
2016
RNF8 Regulates Nonhomologous End Joining and DNA-PK Recruitment to DNA Double-Strand Break Sites
Gao S, Surovtseva Y, Bindra R. RNF8 Regulates Nonhomologous End Joining and DNA-PK Recruitment to DNA Double-Strand Break Sites. International Journal Of Radiation Oncology • Biology • Physics 2016, 96: s55. DOI: 10.1016/j.ijrobp.2016.06.143.Peer-Reviewed Original ResearchDiscovery of mammalian regulators of ribosome biogenesis
Farley K, McCann K, Merkel J, Surovtseva Y, Baserga S. Discovery of mammalian regulators of ribosome biogenesis. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.594.1.Peer-Reviewed Original ResearchRibosome biogenesisNucleolar functionNumber of nucleoliGenome-wide siRNA screenRNA polymerase I transcriptionPre-ribosomal RNAPolymerase I transcriptionMammalian regulatorsChromatin stateNucleolar proteinsRibosomal DNAMammalian cellsProtein regulatorsI transcriptionNew regulatorSiRNA screenBiogenesisNucleolar numberHuman cellsProteinRegulatorNucleoliNew roleCellsNew pathway
2015
Identification and Characterization of Novel DNA Repair Inhibitors as Potential Tumor Cell Radiosensitizers
Jairam V, Sundaram R, Breuer G, Surovtseva Y, Bindra R. Identification and Characterization of Novel DNA Repair Inhibitors as Potential Tumor Cell Radiosensitizers. International Journal Of Radiation Oncology • Biology • Physics 2015, 93: s48. DOI: 10.1016/j.ijrobp.2015.07.116.Peer-Reviewed Original Research
2014
High-Throughput RNAi Screening Platform Identifies Novel Regulators of DNA Double-Strand Break Repair Pathways
Salem A, Surovtseva Y, Sundaram R, Bindra R. High-Throughput RNAi Screening Platform Identifies Novel Regulators of DNA Double-Strand Break Repair Pathways. International Journal Of Radiation Oncology • Biology • Physics 2014, 90: s34-s35. DOI: 10.1016/j.ijrobp.2014.05.146.Peer-Reviewed Original Research
2013
High-Content, High-Throughput Screening for Novel Double-Strand Break Repair Inhibitors
Salem A, Sundaram R, Surovtseva Y, Bindra R. High-Content, High-Throughput Screening for Novel Double-Strand Break Repair Inhibitors. International Journal Of Radiation Oncology • Biology • Physics 2013, 87: s654. DOI: 10.1016/j.ijrobp.2013.06.1732.Peer-Reviewed Original Research
2009
Conserved Telomere Maintenance Component 1 Interacts with STN1 and Maintains Chromosome Ends in Higher Eukaryotes
Surovtseva Y, Churikov D, Boltz K, Song X, Lamb J, Warrington R, Leehy K, Heacock M, Price C, Shippen D. Conserved Telomere Maintenance Component 1 Interacts with STN1 and Maintains Chromosome Ends in Higher Eukaryotes. Molecular Cell 2009, 36: 207-218. PMID: 19854131, PMCID: PMC2768651, DOI: 10.1016/j.molcel.2009.09.017.Peer-Reviewed Original ResearchMeSH KeywordsAnaphaseArabidopsisArabidopsis ProteinsCell Line, TumorChromosomal Proteins, Non-HistoneChromosomes, PlantConserved SequenceEukaryotic CellsGenomic InstabilityHumansIn Situ Hybridization, FluorescenceMutationNucleic Acid ConformationProtein BindingRecombination, GeneticTelomereTelomere-Binding ProteinsConceptsG-overhangsOB-fold domainDNA damage responseArabidopsis mutantsMulticellular organismsHigher eukaryotesTEN1 (CST) complexChromosome endsHuman CTC1Telomere integrityTelomere maintenanceDiverse speciesDamage responseEnd fusionsChromatin bridgesTelomere lossRNAi triggersDevelopmental defectsCTC1Stn1PlantsEukaryotesOrthologsVertebratesMutants
2008
STN1 protects chromosome ends in Arabidopsis thaliana
Song X, Leehy K, Warrington R, Lamb J, Surovtseva Y, Shippen D. STN1 protects chromosome ends in Arabidopsis thaliana. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 19815-19820. PMID: 19064932, PMCID: PMC2604966, DOI: 10.1073/pnas.0807867105.Peer-Reviewed Original ResearchConceptsChromosome end protectionEnd chromosome fusionsOligonucleotide/oligosaccharideSignificant sequence similarityDNA repair machineryDouble-strand breaksDistinct subcomplexesMulticellular eukaryotesTelomere capChromosome fusionsArabidopsis thalianaTelomere proteinsChromosome endsSubtelomeric DNASchizosaccharomyces pombeShelterin componentsTelomere integrityVertebrate telomeresRepair machinerySequence similarityNucleolytic attackTelomere recombinationEnd protectionDevelopmental defectsStn1
2007
Arabidopsis POT1 associates with the telomerase RNP and is required for telomere maintenance
Surovtseva Y, Shakirov E, Vespa L, Osbun N, Song X, Shippen D. Arabidopsis POT1 associates with the telomerase RNP and is required for telomere maintenance. The EMBO Journal 2007, 26: 3653-3661. PMID: 17627276, PMCID: PMC1949013, DOI: 10.1038/sj.emboj.7601792.Peer-Reviewed Original ResearchConceptsTelomere length regulationLength regulationChromosome end protectionSingle-copy geneNovel accessory factorTelomerase RNPTelomere proteinsTelomere maintenanceSequence similarityTelomeric DNAAccessory factorsEnd protectionTelomerase enzymeGenetic analysisSame pathwayUnsynchronized cellsS phaseRapid evolutionTelomerase activityTelomeraseTelomeresGenesProteinRegulationPOT1
2005
The Arabidopsis Pot1 and Pot2 Proteins Function in Telomere Length Homeostasis and Chromosome End Protection
Shakirov E, Surovtseva Y, Osbun N, Shippen D. The Arabidopsis Pot1 and Pot2 Proteins Function in Telomere Length Homeostasis and Chromosome End Protection. Molecular And Cellular Biology 2005, 25: 7725-7733. PMID: 16107718, PMCID: PMC1190295, DOI: 10.1128/mcb.25.17.7725-7733.2005.Peer-Reviewed Original ResearchConceptsChromosome end protectionTelomere length homeostasisEnd protectionLength homeostasisGenome instabilityWild typePot1-like proteinsSevere growth defectOligonucleotide/oligosaccharideMassive genome instabilityBulk telomeresTransgenic plantsGrowth defectProtein functionPositive regulationN-terminusBinding proteinAnalogous regionMutantsArabidopsisPlantsLength controlCorresponding regionPOT1Protein