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/摘要
这项建议的重点是人类造血的遗传决定因素,特别是发展
造血祖细胞(HPCs)及其前体细胞。有相当大的兴趣增加在
从培养的诱导多能干细胞(iPSC)中体外生产HPC,因为这将支持研究和
许多基于血细胞的疗法的发展。为了更好地了解基因和基因组位点,
为了提高体外血细胞产量,我使用计算机建模来分析全基因组的血液性状
关联研究(GWAS)数据。我鉴定并验证了原肌球蛋白1是一种通常抑制细胞增殖的基因。
HPC及其内皮前体细胞的体外产生。在本补助金的目标1中,我将确定
原肌球蛋白1通过明确的体外iPSC调控HPC前体发育的机制
文化模式在目标2中,我将定义其他基因和遗传机制,调节HPC生物学,
互补统计遗传学方法的新适应。
拟议的五年培训计划概述了我作为学术儿科研究生涯的发展
一位寻求开发一项研究计划的医生科学家,该计划调查调节
造血我完成了细胞和分子血液学的医学博士和博士学位,儿科住院医师培训,
我目前在儿童医院接受新生儿和围产期医学研究员培训的第三年,
费城医院(CHOP)拟议的研究将在本杰明的指导下进行
Voight博士,复杂人类遗传学领域的领导者; Stella Chou博士,iPSC衍生的领导者
造血和输血医学;以及Deborah French博士,iPSC操纵的领导者,
造血培养和血细胞生物学。此外,我还得到一个咨询委员会的支持,
相关和互补领域的科学家和医生科学家,他们共同支持
多名K奖学员我已经得到了我所在机构的全力支持,并将受益于
卓越的教学培训,广泛的资源和核心设施,以及世界一流的导师,
CHOP和宾夕法尼亚大学在本奖项期间。在理想的学术培训
K99支持提供的环境将帮助我发展成为独立工作者所需的技能。
在该奖项的R 00阶段研究造血遗传学的医生科学家。
我的目标是经营一个实验室,利用计算和生物化学的方法来了解遗传
增强血液生成的机制和治疗策略。在这份资助中,我将获得严格的
数据科学和造血建模培训。这将扩大我的技能库,推动我的
过渡到独立,并增加我成功竞争R 01资金的可能性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Christopher Stephen Thom其他文献
Christopher Stephen Thom的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 16.74万 - 项目类别:
Research Grant