grant
Investigating the Role of High Fat Diet in Hematopoiesis and Clonal Hematopoiesis
Organization UNIVERSITY OF MICHIGAN AT ANN ARBORLocation ANN ARBOR, UNITED STATESPosted 1 Feb 2025Deadline 31 Jan 2028
NIHUS FederalResearch GrantFY202610 year old10 years of age2-ketoglutarate2-oxoglutarate21+ years old65 and older65 or older65 years of age and older65 years of age or more65 years of age or older65+ years65+ years oldAML - Acute Myeloid LeukemiaAccelerationAcute Myeloblastic LeukemiaAcute Myelocytic LeukemiaAcute Myelogenous LeukemiaAdultAdult HumanAffectAged 65 and OverAgingBloodBlood DiseasesBlood Precursor CellBlood Reticuloendothelial SystemCancersCell BodyCell Communication and SignalingCell SignalingCellsCellular Immune FunctionChronic Myelomonocytic LeukemiaChronic stressClonal expansion of hematopoietic cellsClonal expansion of hematopoietic stem cellsClonal hematopoietic expansionCytokine Signal TransductionCytokine SignalingDNADNA mutationDNMT3aDataData SetDeoxyribonucleic AcidDevelopmentDietDietary FactorsDioxygenasesDiseaseDisease ProgressionDisorderDysmyelopoietic SyndromesElderlyEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessExhibitsExposure toExtramedullary HematopoiesisFe elementFundingGene variantGenesGenetic ChangeGenetic defectGenetic mutationHSC agingHSC regenerationHSC self-renewalHSC transplantationHematologic Body SystemHematologic CancerHematologic DiseasesHematologic MalignanciesHematologic NeoplasmsHematologic Organ SystemHematological DiseaseHematological DisorderHematological MalignanciesHematological NeoplasmsHematological TumorHematopoiesisHematopoieticHematopoietic Body SystemHematopoietic CancerHematopoietic Cell TumorHematopoietic Cellular Control MechanismsHematopoietic MalignanciesHematopoietic NeoplasmsHematopoietic Neoplasms including LymphomasHematopoietic Progenitor CellsHematopoietic Stem Cell TransplantHematopoietic Stem Cell TransplantationHematopoietic SystemHematopoietic TumorHematopoietic and Lymphoid Cell NeoplasmHematopoietic and Lymphoid NeoplasmsHematopoietic stem cellsHigh Fat DietHumanImmune responseIncidenceIndividualIndolentInflammatoryIntracellular Communication and SignalingIronKO miceKnock-outKnock-out MiceKnockoutKnockout MiceLeadLeukemic progenitor and stem cellLinkMalignant Hematologic NeoplasmMalignant Hematopoietic NeoplasmMalignant NeoplasmsMalignant TumorMetabolic stressMiceMice MammalsModelingModern ManMurineMusMutationMyelodysplastic DiseaseMyelodysplastic SyndromesMyelogenousMyeloidMyeloid DiseaseMyeloid MalignancyMyeloid NeoplasmMyeloid TumorMyeloproliferative DisordersMyeloproliferative TumorsMyeloproliferative diseaseNull MouseOnset of illnessOutputPathologyPathway interactionsPatientsPb elementPersonsPlayPopulationPrecancerous ConditionsPrecipitating FactorsPremalignant ConditionPremalignant StatePreventionProgenitor Cell TransplantationProgenitor CellsProliferatingPropertyProteinsRecurrenceRecurrentRefractory Anemia with an Excess of BlastsRefractory anaemia with excess blastsResistanceRiskRoleSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSmoldering LeukemiaSomatic MutationSortingStem Cell TransplantationStem Cell likeStem cell transplantStressT-Cell ActivationTestingTherapeuticToxic effectToxicitiesTransplantationWorkabove age 65accelerated agingaccelerated biological ageaccelerated biological agingactivate T cellsacute granulocytic leukemiaacute myeloid leukemiaacute stressadulthoodadvanced ageafter age 65age 10age 10 yearsage 65 and greaterage 65 and olderage 65 or olderageage accelerationage associatedage associated declineage associated diseaseage associated disorderage associated impairmentage correlatedage dependentage dependent declineage dependent diseaseage dependent disorderage dependent impairmentage linkedage of 65 years onwardage relatedage related declineage related human diseaseage specificage-related diseaseage-related disorderage-related impairmentagedaged 65 and greateraged 65+aged ≥65allelic variantalpha ketoglutaratebiological signal transductionblood cancerblood cell formationblood cell progenitorblood disorderblood progenitorblood stem cellblood stem cell regenerationblood stem cell self-renewalblood stem cell transplantationblood-forming stem cellcancer of bloodcancer of the bloodclinical significanceclinically significantclonal expansions in the bloodclonal hematopoiesisclones in hematopoietic cellscurative interventioncurative therapeuticcurative therapycurative treatmentscytopeniadecline in functiondecline in functional statusdecline with agedemethylationdevelopmentaldietsdisease onsetdisorder onsetearly onsetepigeneticallyexperimentexperimental researchexperimental studyexperimentsfunctional declinefunctional status declinegenetic variantgenome mutationgenomic variantgeriatrichDNA methyltransferase 3aheavy metal Pbheavy metal leadhematopoietic cell cloneshematopoietic cell transplantationhematopoietic cellular transplantationhematopoietic progenitorhematopoietic progenitor cell self-renewalhematopoietic progenitor cell transplantationhematopoietic stem cell aginghematopoietic stem cell clonalityhematopoietic stem cell regenerationhematopoietic stem cell self-renewalhematopoietic stem progenitor cellhemopoietichemopoietic progenitorhemopoietic stem cellhigh riskhost responsehuman old age (65+)immune functionimmune system responseimmunoresponseimprovedinsightleukemialeukemia stem/initiating cellsleukemic progenitorleukemic stem cellleukemic transformationmalignancymortalitymouse modelmurine modelmutantmyelodysplasiamyeloproliferative neoplasmneoplasm/cancernovelover 65 yearspathwayperipheral bloodprecancerous statepreventpreventingprogenitorprogenitor agingprogenitor capacityprogenitor cell agingprogenitor cell functionprogenitor cell likeprogenitor functionprogenitor transplantationprogenitor-likeprogression riskreconstitutereconstitutionregeneration of blood stem cellsresistantrisk stratificationscRNA sequencingscRNA-seqscreeningscreeningsself - renewal in hematopoietic stem cellsself-renewself-renewalsenior citizensingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial rolesomatic variantstem and progenitor cell functionstem and progenitor cell transplantationsstem and progenitor functionstem cell agingstem cell characteristicsstem cell functionstem cellsstem-likestemnessstratify riskten year oldten years of agetransplantα-ketoglutarateα-oxoglutarateαKG≥65 years
Description preview
PROJECT SUMMARY: Aging of the hematopoietic system is accompanied by increase in proliferation but
functional decline of hematopoietic stem cells (HSCs), which often exhibit a bias towards myeloid lineage
differentiation. These changes are thought to be clinically significant, contributing to age-associated declines in
immune function in the…
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