Early Clonal Evolution in Acquired Aplastic Anemia
获得性再生障碍性贫血的早期克隆进化
基本信息
- 批准号:10393146
- 负责人:
- 金额:$ 8.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2022-03-09
- 项目状态:已结题
- 来源:
- 关键词:AdultAdvisory CommitteesAffectAplastic AnemiaAutomobile DrivingAwardBlood CellsBone MarrowCareer MobilityCellsChildClonal EvolutionComplicationDataDevelopment PlansDisease MarkerDisease OutcomeDoctor of MedicineDoctor of PhilosophyEarly DiagnosisEnvironmentFellowshipFosteringFrightGeneral HospitalsGenetic MarkersHematological DiseaseHematologyHematopoiesisHematopoieticHematopoietic NeoplasmsImmune mediated destructionImmunologyInternal MedicineK-Series Research Career ProgramsKnowledgeLifeMalignant - descriptorMassachusettsMedicineMentorsMentorshipMutationOncologyParentsPatientsPennsylvaniaPhysiciansPrevalencePrevention strategyPrincipal InvestigatorRelapseResearchResidenciesResourcesRiskScientistSomatic MutationTrainingTraining ProgramsTreatment FailureUniversitiesbone marrow failure syndromecareer developmentclinically relevantdriver mutationgenetic analysisgenomic biomarkerimprovedleukemiapersonalized medicineprofessorprogramsresearch facilityresponseresponse biomarkerskillsstem cell biologytherapy outcome
项目摘要
PROJECT SUMMARY/ABSTRACT
This K08 Career Development Award proposal describes the candidate’s 5-year training program to become
an independent physician-scientist in academic hematology, with a focus on bone marrow failure syndromes.
The Principal Investigator (PI) has completed M.D. and Ph.D. Degrees at the University of Pennsylvania
(Penn), followed by residency training in Internal Medicine at the Massachusetts General Hospital, fellowship
training in Hematology-Oncology at Penn, and is currently an Assistant Professor in Medicine at the University
of Pennsylvania. Through the 5-year career development plan of the parent K08 award, the PI will expand her
knowledge and research skills in hematopoiesis, stem cell biology, and immunology in order to develop an
independent research program studying clonal hematopoiesis in acquired aplastic anemia (aAA). The PI will be
mentored by Dr. Peter Klein, an expert on hematopoiesis, as well as the Advisory Committee, who will foster
PI’s scientific and career development.
The proposed research focuses on aAA, a life-threatening blood disease affecting children and adults caused
by immune destruction of early hematopoietic cells. Clonal evolution to leukemia is a common complication, with
no effective prevention strategy available. Emerging data indicate that up to a quarter of aAA patients acquire
somatic mutations and may be at a greater risk of malignant transformation. Therefore, understanding clonal
hematopoiesis in aAA is important to allow for early detection and improved therapies. The objective of the K08
award is to characterize the full spectrum of clonal hematopoiesis in aAA and to dissect the mechanisms driving
emergence of clones. This will be accomplished in three specific aims: 1) Characterize the landscape and
prevalence of somatic mutations in the bone marrow of aAA patients using an unbiased genetic analysis, 2)
Identify genomic biomarkers of response to therapy and disease outcomes, and 3) Characterize the function of
candidate driver mutations in hematopoiesis. The successful completion of this project is expected to have a
sustained and lasting impact in the field by providing an understanding of clinically relevant somatic alterations
in aAA, which could serve as genetic biomarkers and targets for new personalized therapies. The strong scientific
expertise and the mentorship track record of the PI’s Mentor and Advisory Committee, together with the unique
resources and outstanding research facilities at Penn, make this an ideal environment for this K08 Award. This
research program, performed in the context of a comprehensive career development plan, will support the PI’s
career transition to become an independent physician-scientist in Hematology.
项目概要/摘要
该 K08 职业发展奖提案描述了候选人的 5 年培训计划,以成为
学术血液学领域的独立医师科学家,专注于骨髓衰竭综合征。
首席研究员 (PI) 已在宾夕法尼亚大学获得医学博士和博士学位。
(宾夕法尼亚大学),随后在马萨诸塞州总医院接受内科住院医师培训,获得奖学金
在宾夕法尼亚大学接受血液肿瘤学培训,目前是该大学的医学助理教授
通过母公司 K08 奖项的 5 年职业发展计划,PI 将拓展她的职业生涯。
造血、干细胞生物学和免疫学方面的知识和研究技能,以开发
研究获得性再生障碍性贫血(aAA)中的克隆造血的独立研究项目将是。
由造血学专家 Peter Klein 博士以及咨询委员会指导,他们将培养
PI 的科学和职业发展。
拟议的研究重点是 aAA,这是一种影响儿童和成人的危及生命的血液疾病。
通过免疫破坏早期造血细胞克隆进化为白血病是一种常见的并发症。
没有有效的预防策略可用,新数据表明多达四分之一的 aAA 患者患有此病。
因此,了解克隆性体细胞突变可能会面临更大的恶变风险。
aAA 中的造血对于早期检测和改进治疗非常重要 K08 的目标。
该奖项旨在描述 AAA 中克隆造血的全谱,并剖析驱动机制
这将通过三个具体目标来实现:1)描绘景观特征并
使用无偏见的遗传分析得出 aAA 患者骨髓中体细胞突变的患病率,2)
识别治疗反应和疾病结果的基因组生物标志物,以及 3) 表征
该项目的成功完成预计将产生造血驱动候选突变。
通过提供对临床相关体细胞改变的理解,在该领域产生持续和持久的影响
在 aAA 中,它可以作为新的个性化疗法的遗传生物标志物和目标。
PI 导师和咨询委员会的专业知识和指导记录,以及独特的
宾夕法尼亚大学的资源和出色的研究设施,使其成为 K08 奖的理想环境。
在全面职业发展计划的背景下进行的研究计划将支持 PI
职业转型成为血液学领域的独立医师科学家。
项目成果
期刊论文数量(24)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Recent advances in understanding clonal haematopoiesis in aplastic anaemia.
了解再生障碍性贫血中克隆造血的最新进展。
- DOI:
- 发表时间:2017-05
- 期刊:
- 影响因子:6.5
- 作者:Stanley, Natasha;Olson, Timothy S;Babushok, Daria V
- 通讯作者:Babushok, Daria V
Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia.
CPX-351 与维奈托克和阿扎胞苷在急性髓系白血病中的真实疗效。
- DOI:
- 发表时间:2022-07-12
- 期刊:
- 影响因子:7.5
- 作者:Matthews, Andrew H;Perl, Alexander E;Luger, Selina M;Loren, Alison W;Gill, Saar I;Porter, David L;Babushok, Daria V;Maillard, Ivan P;Carroll, Martin P;Frey, Noelle V;Hexner, Elizabeth O;Martin, Mary Ellen;McCurdy, Shannon R;Stadtmauer, Edward
- 通讯作者:Stadtmauer, Edward
Born to RUNX1.
为RUNX1而生。
- DOI:
- 发表时间:2020
- 期刊:
- 影响因子:20.3
- 作者:Sung, Pamela J;Babushok, Daria V
- 通讯作者:Babushok, Daria V
Germline POT1 variants can predispose to myeloid and lymphoid neoplasms.
种系 POT1 变异可能导致骨髓和淋巴肿瘤。
- DOI:
- 发表时间:2022
- 期刊:
- 影响因子:11.4
- 作者:Lim, Tristan L;Lieberman, David B;Davis, Adam R;Loren, Alison W;Hausler, Ryan;Bigdeli, Ashkan;Li, Yimei;Powers, Jacquelyn;Raper, Anna;Regeneron Genetics Center;Carty, Shannon A;Nathanson, Katherine L;Bagg, Adam;Hexner, Elizabeth O;Maxwell, K
- 通讯作者:Maxwell, K
Inducible Sbds deletion impairs bone marrow niche capacity to engraft donor bone marrow after transplantation.
诱导性 Sbds 缺失会损害移植后骨髓微环境植入供体骨髓的能力。
- DOI:
- 发表时间:2022
- 期刊:
- 影响因子:7.5
- 作者:Zha, Ji;Kunselman, Lori K;Xie, Hongbo M;Ennis, Brian;Shah, Yash B;Qin, Xia;Fan, Jian;Babushok, Daria V;Olson, Timothy S
- 通讯作者:Olson, Timothy S
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Daria Babushok其他文献
Daria Babushok的其他文献
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{{ truncateString('Daria Babushok', 18)}}的其他基金
The effects of somatic HLA class I allele mutations on antigen presentation in acquired aplastic anemia
体细胞 HLA I 类等位基因突变对获得性再生障碍性贫血抗原呈递的影响
- 批准号:
10545024 - 财政年份:2022
- 资助金额:
$ 8.88万 - 项目类别:
The effects of somatic HLA class I allele mutations on antigen presentation in acquired aplastic anemia
体细胞 HLA I 类等位基因突变对获得性再生障碍性贫血抗原呈递的影响
- 批准号:
10347646 - 财政年份:2022
- 资助金额:
$ 8.88万 - 项目类别:
Early Clonal Evolution in Acquired Aplastic Anemia
获得性再生障碍性贫血的早期克隆进化
- 批准号:
9276506 - 财政年份:2016
- 资助金额:
$ 8.88万 - 项目类别:
Early Clonal Evolution in Acquired Aplastic Anemia
获得性再生障碍性贫血的早期克隆进化
- 批准号:
9089365 - 财政年份:2016
- 资助金额:
$ 8.88万 - 项目类别:
Early Clonal Evolution in Acquired Aplastic Anemia
获得性再生障碍性贫血的早期克隆进化
- 批准号:
9923728 - 财政年份:2016
- 资助金额:
$ 8.88万 - 项目类别:
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