2022
Emerging frontiers in immuno- and gene therapy for cancer
Gustafson MP, Ligon JA, Bersenev A, McCann CD, Shah NN, Hanley PJ. Emerging frontiers in immuno- and gene therapy for cancer. Cytotherapy 2022, 25: 20-32. PMID: 36280438, PMCID: PMC9790040, DOI: 10.1016/j.jcyt.2022.10.002.Peer-Reviewed Original ResearchA genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy
Ye L, Park JJ, Peng L, Yang Q, Chow RD, Dong MB, Lam SZ, Guo J, Tang E, Zhang Y, Wang G, Dai X, Du Y, Kim HR, Cao H, Errami Y, Clark P, Bersenev A, Montgomery RR, Chen S. A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy. Cell Metabolism 2022, 34: 595-614.e14. PMID: 35276062, PMCID: PMC8986623, DOI: 10.1016/j.cmet.2022.02.009.Peer-Reviewed Original ResearchConceptsCAR T cellsT cell-based immunotherapyRight molecular targetCell-based immunotherapyCAR-T therapyChimeric antigen receptorMultiple cancer modelsCAR-T efficacyFunction CRISPR screensCD8 TPrimary CD8Immune functionImmunological diseasesImmune boosterCancer modelAntigen receptorDistinct gene expressionMolecular targetsCRISPR activation screensMetabolic programsImmunological analysisTherapyCancerEfficacyActivation screens
2021
ISCT survey on hospital practices to support externally manufactured investigational cell-gene therapy products
Bersenev A, Gustafson MP, Hanley PJ. ISCT survey on hospital practices to support externally manufactured investigational cell-gene therapy products. Cytotherapy 2021, 24: 27-31. PMID: 34810083, DOI: 10.1016/j.jcyt.2021.09.009.Peer-Reviewed Original ResearchDelivering externally manufactured cell and gene therapy products to patients: perspectives from the academic center experience
Hanley PJ, Bersenev A, Gustafson MP. Delivering externally manufactured cell and gene therapy products to patients: perspectives from the academic center experience. Cytotherapy 2021, 24: 16-18. PMID: 34753676, DOI: 10.1016/j.jcyt.2021.09.010.Peer-Reviewed Original Research
2020
Expansion of human mesenchymal stem/stromal cells (hMSCs) in bioreactors using microcarriers: lessons learnt and what the future holds
Couto P, Rotondi M, Bersenev A, Hewitt C, Nienow A, Verter F, Rafiq Q. Expansion of human mesenchymal stem/stromal cells (hMSCs) in bioreactors using microcarriers: lessons learnt and what the future holds. Biotechnology Advances 2020, 45: 107636. PMID: 32980437, DOI: 10.1016/j.biotechadv.2020.107636.Peer-Reviewed Original ResearchConceptsHuman mesenchymal stem/stromal cellsGene therapy applicationsManufacturing processMesenchymal stem/stromal cellsStem/stromal cellsCurrent engineering challengesTherapy applicationsImproved process monitoringMulti-differentiation capabilitiesProcess efficiencyEngineering challengesMicrocarriersProcess monitoringProcess variabilityBioreactorHuman operationProduction costsPotential future areasGood consistencyCartilage repairFinal productAffordable priceCellular interventionsRelevant scalesCell qualityAnalysis of the clinical landscape for genetically-modified cellular immunotherapies highlights the need for optimized and consistent manufacturing processes
Hood T, Bersenev A, Smith D, Heathman T, Rafiq Q. Analysis of the clinical landscape for genetically-modified cellular immunotherapies highlights the need for optimized and consistent manufacturing processes. Cytotherapy 2020, 22: s36. DOI: 10.1016/j.jcyt.2020.03.028.Peer-Reviewed Original ResearchChapter 2 Process development and manufacturing approaches for mesenchymal stem cell therapies
Couto P, Bersenev A, Rafiq Q. Chapter 2 Process development and manufacturing approaches for mesenchymal stem cell therapies. 2020, 33-71. DOI: 10.1016/b978-0-12-816221-7.00002-1.Peer-Reviewed Original Research
2016
Gene therapy applications to transfusion medicine
Gehrie E, Bersenev A, Bruscia E, Krause D, Schulz W. Gene therapy applications to transfusion medicine. 2016, 452-455. DOI: 10.1002/9781119013020.ch38.ChaptersGene therapyTherapeutic genetic materialGene therapy applicationsTranscription activator-like effector nucleasesZinc finger nucleasesPackaging cell lineGene-modified cellsGene-editing approachesNonviral techniquesTherapy applicationsFinger nucleasesEffector nucleasesViral vectorsShort palindromic repeatsVector systemReplication-competent virusPalindromic repeatsHemophilia BPossible applicationsGenetic materialNucleaseApplicationsGenetic diseasesFactor IXVector
2015
Chimeric antigen receptor modified T cells directed against CD19 (CTL019) induce clinical responses in patients with relapsed or refractory CD19+ lymphomas
Levine B, Svoboda J, Nasta S, Porter D, Chong E, Lacey S, Mahnke Y, Melenhorst J, Chew A, Shah G, Hasskar J, Wasik M, Landsburg D, Mato A, Garfall A, Frey N, Shaw P, Marcucci K, Shea J, McConville H, Manvar N, O'Rourke M, Lamontagne A, Bersenev A, Zheng Z, Schuster S, June C. Chimeric antigen receptor modified T cells directed against CD19 (CTL019) induce clinical responses in patients with relapsed or refractory CD19+ lymphomas. Cytotherapy 2015, 17: s13. DOI: 10.1016/j.jcyt.2015.03.327.Peer-Reviewed Original Research
2010
14-3-3 Regulates the Lnk/JAK2 Pathway In Hematopoietic Stem and Progenitor Cells
Balcerek J, Jiang J, Bersenev A, Song Y, Wu C, Tong W. 14-3-3 Regulates the Lnk/JAK2 Pathway In Hematopoietic Stem and Progenitor Cells. Blood 2010, 116: 86. DOI: 10.1182/blood.v116.21.86.86.Peer-Reviewed Original ResearchOncogenic JAK2HSPC expansionHematopoietic stemRegulation of JAK2Serine phosphorylation eventsTyrosine kinase JAK2Progenitor cell homeostasisLymphocyte adaptor proteinHSPC developmentPhosphorylation eventsAdaptor proteinScaffold proteinCellular processesSerine residuesKinase JAK2Lnk-/- miceGene productsCritical binding siteRegulatory mechanismsCell homeostasisHSPC homeostasisJAK2 activityInactive stateFunction mutationsJAK2 pathway
2009
Lnk Constrains Oncogenic JAK2-Induced Myeloproliferative Disease in Mice.
Bersenev A, Wu C, Balcerek J, Tong W. Lnk Constrains Oncogenic JAK2-Induced Myeloproliferative Disease in Mice. Blood 2009, 114: 1437. DOI: 10.1182/blood.v114.22.1437.1437.Peer-Reviewed Original ResearchOncogenic JAK2TPO stimulationHematopoietic stem cell homeostasisDownstream signal transduction pathwaysStem cell homeostasisAdaptor protein LNKSignal transduction pathwaysPhysiological negative regulatorCell surface receptorsImportant signaling axisWild-type bone marrow cellsDouble mutantTransduction pathwaysJAK2 activationHSC poolLNK deficiencyNegative regulatorJanus kinaseCell homeostasisCell developmentCytokine receptorsSignaling AxisJAK2 pathwayChromosomal translocationsMPD developmentFOG-1 Requires NuRD to Promote Hematopoiesis and Maintain Lineage Fidelity within the Megakaryocytic–Erythroid Compartment.
Gregory G, Miccio A, Bersenev A, Wang Y, Hong W, Zhang Z, Poncz M, Tong W, Blobel G. FOG-1 Requires NuRD to Promote Hematopoiesis and Maintain Lineage Fidelity within the Megakaryocytic–Erythroid Compartment. Blood 2009, 114: 702. DOI: 10.1182/blood.v114.22.702.702.Peer-Reviewed Original ResearchMegakaryocyte-erythroid progenitorsMast cell gene expressionCell gene expressionFOG-1Mast cell genesGATA-1Gene expressionLineage fidelityErythroid cellsCell genesGenome-wide transcriptome analysisTranscription factor GATA-1Epigenetic silencing mechanismsWide transcriptome analysisCofactor FOG-1Mast cell-specific genesStage-specific rolesCell-specific genesNuRD complexNucleosome remodelingGATA factorsSilencing mechanismNuRDTranscriptome analysisHematopoietic development
2008
Lnk Controls Hematopoietic Stem Cell Self-Renewal through Direct Interactions with JAK2 and Contributes to Oncogenic JAK2-Induced Myeloproliferative Diseases in Mice
Bersenev A, Wu C, Balcerek J, Tong W. Lnk Controls Hematopoietic Stem Cell Self-Renewal through Direct Interactions with JAK2 and Contributes to Oncogenic JAK2-Induced Myeloproliferative Diseases in Mice. Blood 2008, 112: 895. DOI: 10.1182/blood.v112.11.895.895.Peer-Reviewed Original ResearchOncogenic JAK2TPO stimulationHematopoietic stem cell homeostasisStem Cell Self-RenewalHematopoietic Stem Cell Self-RenewalDownstream signal transduction pathwaysStem cell homeostasisPhosphorylated tyrosine residuesAdaptor protein LNKCell Self-RenewalSignal transduction pathwaysPhysiological negative regulatorCell surface receptorsImportant signaling axisWild-type HSCsTransduction pathwaysGenetic evidenceJAK2 activationSelf-RenewalBiochemical experimentsLNK deficiencyNegative regulatorHSC poolHSC quiescenceJanus kinaseThe GATA-1 Cofactor FOG-1 Recruits NuRD to Promote Normal Erythroid and Megakaryocyte Development and Maintain Lineage Fidelity by Restricting Mast Cell Gene Expression.
Gregory G, Wang Y, Hong W, Miccio A, Bersenev A, Yu X, Wang H, Choi J, Shelat S, Tong W, Poncz M, Blobel G. The GATA-1 Cofactor FOG-1 Recruits NuRD to Promote Normal Erythroid and Megakaryocyte Development and Maintain Lineage Fidelity by Restricting Mast Cell Gene Expression. Blood 2008, 112: 1373. DOI: 10.1182/blood.v112.11.1373.1373.Peer-Reviewed Original ResearchGATA-1/FOGFOG-1Megakaryocytic-erythroid progenitorsMast cell gene expressionCell gene expressionErythroid cellsGene expressionMegakaryocyte developmentCell lineagesLineage-specific transcription factorsLevel of GATA2Mast cell fateTissue-specific nuclear factorsGATA-1 activityCo-repressor complexCofactor FOG-1Mast cell genesMast cell-specific genesCell-specific genesGene expression patternsMast cell lineageMature erythroid cellsNucleosome remodelingCell fateGATA-1