Adam Krysztofiak, PhD
Postdoctoral FellowCards
About
Research
Overview
Medical Research Interests
Biochemistry; Cell Biology; DNA Breaks; DNA Damage; DNA Repair; Molecular Biology; Proton Therapy; Radiation Oncology; Radiation, Ionizing; Radiobiology; Radiotherapy
Public Health Interests
Metabolism; Pharmaceuticals and Medical Devices; Cancer
Publications
Featured Publications
Direct targeting of amplified gene loci for proapoptotic anticancer therapy
Kaushik Tiwari M, Colon-Rios DA, Tumu HCR, Liu Y, Quijano E, Krysztofiak A, Chan C, Song E, Braddock DT, Suh HW, Saltzman WM, Rogers FA. Direct targeting of amplified gene loci for proapoptotic anticancer therapy. Nature Biotechnology 2021, 40: 325-334. PMID: 34711990, PMCID: PMC8930417, DOI: 10.1038/s41587-021-01057-5.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksTriplex-forming oligonucleotidesDNA damage responseDouble-strand breaksDrug resistanceGene amplificationP53-independent apoptosisHER2-positive breastOvarian cancer modelHuman tumor xenograftsInduction of apoptosisGenomic lociNumber of drugsCellular functionsDamage responseGene locusProtein productsHER2-positive cancer cellsDriver genesClinical efficacyCombat drug resistanceDNA damageHER2 amplificationTherapeutic strategiesTumor xenograftsMetabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown
Krysztofiak A, Szymonowicz K, Hlouschek J, Xiang K, Waterkamp C, Larafa S, Goetting I, Vega-Rubin-de-Celis S, Theiss C, Matschke V, Hoffmann D, Jendrossek V, Matschke J. Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown. IScience 2021, 24: 103366. PMID: 34825138, PMCID: PMC8603201, DOI: 10.1016/j.isci.2021.103366.Peer-Reviewed Original ResearchCommon metabolic responseCompensatory glycolysisDSB repair kineticsMitochondrial respiratory chainRepair kineticsRadiation-induced DNAFuture mechanistic studiesDNA repairDNA repair kineticsRespiratory chainCancer metabolismMitochondrial functionStress conditionsMetabolic vulnerabilitiesCancer cell linesMetabolic targetsCancer cellsCell linesMitochondrial recoveryGlycolysisNew hypothesisMetabolic responseMetabolismMechanistic studiesDiscoveryVulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair
Dow J, Krysztofiak A, Liu Y, Colon-Rios DA, Rogers FA, Glazer PM. Vulnerability of IDH1-Mutant Cancers to Histone Deacetylase Inhibition via Orthogonal Suppression of DNA Repair. Molecular Cancer Research 2021, 19: 2057-2067. PMID: 34535560, PMCID: PMC8642278, DOI: 10.1158/1541-7786.mcr-21-0456.Peer-Reviewed Original ResearchConceptsHistone deacetylase inhibitor vorinostatPatient-derived tumor xenograftsHomology-directed repairIsocitrate dehydrogenase 1/2 mutationsHistone deacetylase inhibitionIDH1 mutant cellsGreater cell deathHDACi treatmentInhibitor vorinostatTumor xenograftsDeacetylase inhibitionIDH1/2 mutationsPotential biomarkersSpecific cancersMutant cancersCancerCancer cellsDNA repair defectsMalignancyVorinostatDNA double-strand breaksGliomasHistone hypermethylationCell deathPARPiProton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining
Szymonowicz K, Krysztofiak A, van der Linden J, Kern A, Deycmar S, Oeck S, Squire A, Koska B, Hlouschek J, Vüllings M, Neander C, Siveke J, Matschke J, Pruschy M, Timmermann B, Jendrossek V. Proton Irradiation Increases the Necessity for Homologous Recombination Repair Along with the Indispensability of Non-Homologous End Joining. Cells 2020, 9: 889. PMID: 32260562, PMCID: PMC7226794, DOI: 10.3390/cells9040889.Peer-Reviewed Original ResearchHigh-throughput Evaluation of Protein Migration and Localization after Laser Micro-Irradiation
Oeck S, Malewicz NM, Krysztofiak A, Turchick A, Jendrossek V, Glazer PM. High-throughput Evaluation of Protein Migration and Localization after Laser Micro-Irradiation. Scientific Reports 2019, 9: 3148. PMID: 30816253, PMCID: PMC6395640, DOI: 10.1038/s41598-019-39760-8.Peer-Reviewed Original ResearchConceptsDNA damage sitesDNA repair proteinsProtein of interestHistone dynamicsHistone phosphorylationProtein fociHigh-throughput analysisProtein modificationRepair proteinsDNA damageDamage sitesSingle nucleusMultiple fluorescence channelsHigh-throughput evaluationRepair kineticsProtein migrationProteinAnalysis of accumulationFluorescence channelsPhosphorylationDNACellsAccumulationLocalizationMigration
2024
Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition
Rackear M, Quijano E, Ianniello Z, Colón-Ríos D, Krysztofiak A, Abdullah R, Liu Y, Rogers F, Ludwig D, Dwivedi R, Bleichert F, Glazer P. Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition. Oncotarget 2024, 15: 699-713. PMID: 39352803, PMCID: PMC11444335, DOI: 10.18632/oncotarget.28651.Peer-Reviewed Original ResearchConceptsTumor targetingMonoclonal antibody therapyTumor-specific targetingCell uptakeNucleic acid bindingCell surface antigensAntibody therapyHuman variantsClinical successCell-penetrating antibodiesAcid bindingSystemic administrationSurface antigensTumorRAD51 inhibitionAntibody platformMechanism of cell penetrationBind RAD51AntibodiesFull-lengthSpecific targetsCell penetrationDisease targetsCellsAutoantibodies
2022
The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus
Jimenez-Sainz J, Krysztofiak A, Garbarino J, Rogers F, Jensen RB. The Pathogenic R3052W BRCA2 Variant Disrupts Homology-Directed Repair by Failing to Localize to the Nucleus. Frontiers In Genetics 2022, 13: 884210. PMID: 35711920, PMCID: PMC9197106, DOI: 10.3389/fgene.2022.884210.Peer-Reviewed Original ResearchDominant-negative alleleDNA damage responseDNA repair functionDNA strand exchangeHomology-directed repairGenome instabilityCellular functionsDamage responseDNA bindingNegative allelesStrand exchangeRepair functionGermline missense variantsCell survivalFunction mutationsMissense variantsRAD51Pathogenic allelesSimple lossPARP inhibitorsCytoplasmProteinAllelesHomologyDNA
2018
Relating Linear Energy Transfer to the Formation and Resolution of DNA Repair Foci After Irradiation with Equal Doses of X-ray Photons, Plateau, or Bragg-Peak Protons
Oeck S, Szymonowicz K, Wiel G, Krysztofiak A, Lambert J, Koska B, Iliakis G, Timmermann B, Jendrossek V. Relating Linear Energy Transfer to the Formation and Resolution of DNA Repair Foci After Irradiation with Equal Doses of X-ray Photons, Plateau, or Bragg-Peak Protons. International Journal Of Molecular Sciences 2018, 19: 3779. PMID: 30486506, PMCID: PMC6320817, DOI: 10.3390/ijms19123779.Peer-Reviewed Original ResearchRestraining Akt1 Phosphorylation Attenuates the Repair of Radiation-Induced DNA Double-Strand Breaks and Reduces the Survival of Irradiated Cancer Cells
Szymonowicz K, Oeck S, Krysztofiak A, van der Linden J, Iliakis G, Jendrossek V. Restraining Akt1 Phosphorylation Attenuates the Repair of Radiation-Induced DNA Double-Strand Breaks and Reduces the Survival of Irradiated Cancer Cells. International Journal Of Molecular Sciences 2018, 19: 2233. PMID: 30065170, PMCID: PMC6121313, DOI: 10.3390/ijms19082233.Peer-Reviewed Original ResearchConceptsDSB repairLong-term colony formation assaysDNA double-strand break repairDouble-strand break repairKinase-protein kinase BPhosphorylation-deficient mutantKey phosphorylation sitesDNA damage responseEssential subcellular processesProtein kinase BDSB repair kineticsCancer cellsCellular radiation responseActivation stateMurine prostate cancer cellsColony formation assaysEffector proteinsGenotoxic stressPhosphorylation sitesDamage responseBreak repairGenetic approachesThreonine 308Serine 473Kinase B
2017
The Focinator v2-0 Graphical Interface, Four Channels, Colocalization Analysis and Cell Phase Identification
Oeck S, Malewicz NM, Hurst S, Al-Refae K, Krysztofiak A, Jendrossek V. The Focinator v2-0 Graphical Interface, Four Channels, Colocalization Analysis and Cell Phase Identification. Radiation Research 2017, 188: 114-120. PMID: 28492345, DOI: 10.1667/rr14746.1.Peer-Reviewed Original Research
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Therapeutic Radiology
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New Haven, CT 06520
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New Haven, CT 06510
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