Determining genetic mechanisms that drive in vitro hematopoiesis
确定驱动体外造血的遗传机制
基本信息
- 批准号:10453654
- 负责人:
- 金额:$ 16.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-20 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:ActinsAddressAdvisory CommitteesAgingAwardBiochemicalBioinformaticsBiologyBloodBlood CellsBlood PlateletsBlood TransfusionCRISPR/Cas technologyCandidate Disease GeneCell LineCell TherapyCell modelCellsCellular biologyChildhoodChromatinCommunicable DiseasesComplexComputer ModelsCore FacilityDataData ScienceDevelopmentDisease OutbreaksDoctor of PhilosophyEndothelial CellsEndotheliumEnvironmentEpigenetic ProcessErythrocytesFellowshipFundingGene ExpressionGenerationsGenesGeneticGenetic DeterminismGenetic studyGoalsGrantHealthcare SystemsHematopoiesisHematopoieticHematopoietic stem cellsHumanHuman GeneticsIn VitroInstitutionIsoantibodiesK-Series Research Career ProgramsKnock-outLaboratoriesLinkMapsMegakaryocytesMentorshipModelingMolecularMolecular and Cellular BiologyNeonatalOther GeneticsPathway interactionsPatientsPediatric HospitalsPediatricsPennsylvaniaPhasePhiladelphiaPhysiciansProductionQuantitative Trait LociReagentResearchResearch SupportResidenciesResourcesRoleRunningScientistSecureSingle Nucleotide PolymorphismSiteSourceStem Cell DevelopmentSurfaceSystemTechniquesTherapeuticTrainingTraining ProgramsTransfusionTranslational ResearchTropomyosinUnited States National Institutes of HealthUniversitiesValidationVariantWhite Blood Cell Count procedurebaseblood productcareercausal variantcell typeclinically relevantgenetic approachgenetic testinggenome wide association studygenome-widegenomic datagenomic locushematopoietic differentiationhuman modelimprovedinduced pluripotent stem cellinduced pluripotent stem cell technologyinterestknock-downmolecular hematologymultidisciplinarynext generation sequencingnoveloverexpressionperinatal medicineprecursor cellpredictive modelingprogramsresearch and developmentsingle-cell RNA sequencingskillssmall hairpin RNAstem cellssuccesstraittransfusion medicine
项目摘要
PROJECT SUMMARY/ABSTRACT
This proposal focuses on genetic determinants underlying human hematopoiesis, specifically the development
of hematopoietic progenitor cells (HPCs) and their precursors. There is considerable interest in augmenting in
vitro HPC production from cultured induced pluripotent stem cells (iPSCs), as this would support research and
development of many blood cell-based therapies. To better understand genes and genomic loci that might
improve in vitro blood cell yields, I used computational modeling to analyze blood trait genome wide
association study (GWAS) data. I identified and validated Tropomyosin 1 as a gene that normally constrains in
vitro production of HPCs and their endothelial precursor cells. In Aim 1 of this grant, I will determine
mechanisms by which Tropomyosin 1 regulates HPC precursor development using well-defined in vitro iPSC
culture models. In Aim 2, I will define other genes and genetic mechanisms that regulate HPC biology using
novel adaptations of complementary statistical genetics approaches.
The proposed five-year training program outlines development of my research career as an academic pediatric
physician-scientist seeking to develop a research program investigating genetic mechanisms that regulate
hematopoiesis. I completed an MD and PhD in cell and molecular hematology, pediatrics residency training,
and am currently in my third year of fellowship training in neonatal and perinatal medicine at the Children’s
Hospital of Philadelphia (CHOP). The proposed research will be carried out under the mentorship of Benjamin
Voight, PhD, a leader in the field of complex human genetics; Stella Chou, MD, a leader in iPSC-derived
hematopoiesis and transfusion medicine; and Deborah French, PhD, a leader in iPSC manipulation,
hematopoietic culture, and blood cell biology. In addition, I am supported by an advisory committee composed
of scientists and physician-scientists in relevant and complementary fields, who have together supported
multiple K-award trainees. I have secured complete support from my institution, and will benefit from
exceptional didactic training, extensive resources and core facilities, and world-class mentorship available at
CHOP and the University of Pennsylvania for the duration of this award period. Training in an ideal academic
environment, afforded by K99 support, will help me develop the skills required to become an independent
physician-scientist studying hematopoiesis genetics during the R00 phase of this award.
My goal is to run a laboratory that uses computational and biochemical approaches to understand genetic
mechanisms and therapeutic strategies that enhance blood production. In this grant, I will obtain rigorous
training in data science and hematopoiesis modeling. This will expand my repertoire of skills, propel my
transition to independence, and increase my likelihood of success competing for R01 funding.
项目总结/文摘
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Christopher Stephen Thom', 18)}}的其他基金
Determining genetic mechanisms that drive in vitro hematopoiesis
确定驱动体外造血的遗传机制
- 批准号:
10657623 - 财政年份:2021
- 资助金额:
$ 16.74万 - 项目类别:
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