Simulating persistence and elimination of the HIV reservoir
模拟 HIV 病毒库的持续存在和消除
基本信息
- 批准号:10668319
- 负责人:
- 金额:$ 12.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-08-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAdvisory CommitteesAnatomyAntigensArchivesAutomobile DrivingAwardBindingBiological AssayBiological MarkersCD4 Positive T LymphocytesCell ProliferationCellsCollaborationsCommunicationDNADNA SequenceDNA-Directed DNA PolymeraseDataData SetDedicationsDevelopmentEcologyEnsureEpidemicEvolutionExcisionFaceFinancial HardshipFutureGenesGeneticGoalsHIVHIV InfectionsHumanImmunologicsImmunologyIndividualInfectionKnowledgeLaboratoriesLawsLearningLymphocyteMaintenanceMemoryMentorsMentorshipMethodsModelingModernizationNatureNon-linear ModelsPersonsPhylogenetic AnalysisPhysicsPlayPopulation DynamicsPrimary InfectionProcessProgram SustainabilityProliferatingPublishingRNA-Directed DNA PolymeraseRegimenResearchResearch InstituteResearch PersonnelResearch TrainingResolutionResource-limited settingRoleSan FranciscoSequence AnalysisStatistical ModelsStructureT-Cell ProliferationT-LymphocyteT-Lymphocyte SubsetsTestingTimeTrainingTraining ProgramsTreesUniversitiesViralViral Load resultVirus IntegrationVirus LatencyVirus ReplicationWorkantiretroviral therapybiological researchbiomarker discoverycareercohortcurative treatmentsdesigndiverse datagene therapyhuman dataimprovedin silicoinfectious disease modelintegration sitemathematical modelmemory CD4 T lymphocytemortalitynovelresponseside effectskillssocial stigmastandard of carestatisticssuccesssymposiumtoolvirology
项目摘要
PROJECT SUMMARY/ABSTRACT
This proposal describes a five-year research training program that will allow Dr Reeves to transition from a
quantitative researcher in physics and achieve his long-term goal of becoming an independent biomedical
researcher. Dr Reeves will develop a phylodynamic mathematical model, validated on diverse experimental
data, to improve the understanding of the creation, persistence, and elimination of the HIV reservoir.
The training program incorporates the expertise of an outstanding group of mentors and collaborators.
Dr Reeves’s scientific advisory committee includes experts in modeling infectious diseases (Dr Josh Schiffer),
HIV cure (Dr Keith Jerome), viral evolution (Drs Morgane Rolland and Trevor Bedford), HIV reservoirs (Drs
Robert Siliciano and Peter Hunt), and statistics (Dr Peter Gilbert). This group is dedicated to ensuring the
success of this project and the development of Dr Reeves’ career as an independent researcher. The proposal
also contains professional mentorship (Dr Karen Peterson). The specific learning goals required for a
successful transition to biological research will be accomplished through didactic coursework in virology,
immunology, and phylogenetics as well as conferences and professional training in the skills of a successful
mentor and group leader.
Currently, no cure for HIV exists. Individuals living with HIV face the difficult prescription of a lifetime of
daily antiretroviral therapy (ART). Understanding the persistence of HIV during ART is the paramount scientific
question standing between standard of care treatment and cure. Aim 1 is directed at developing a
phylodynamic model of primary infection and the creation of the HIV reservoir. The model will be validated
against viral load and sequence data from the RV217 trial, the highest-resolution primary infection cohort
recorded (shared by Dr Rolland). Dr Reeves has recently published a model in Nature Communications that
suggests the majority of reservoir persistence is due to cellular proliferation of infected cells. Aim 2 is a logical
continuation of this work. Dr Reeves will model T cell subset and phylogenetic data (shared by Drs Hunt and
Siliciano) to refine the mechanism as predominantly homeostatic vs antigenic proliferation. For Aim 3 Dr
Reeves will use the phylodynamic model as a biomarker discovery tool for curative interventions including
latency reversing agents, anti-proliferative therapy, and gene therapy.
Through accomplishing the aims of this proposal, Dr Reeves will address critical gaps in our knowledge
of the HIV reservoir’s persistence and provide a framework to study HIV cure regimens in silico. Ultimately, this
proposal will allow Dr Reeves to influence the future of HIV cure research as well as build a self-sustaining
program at the interface of mathematical modeling, immunology, and viral evolution.
项目总结/文摘
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Multi-scale modelling reveals that early super-spreader events are a likely contributor to novel variant predominance.
- DOI:10.1098/rsif.2021.0811
- 发表时间:2022-04
- 期刊:
- 影响因子:0
- 作者:Goyal A;Reeves DB;Schiffer JT
- 通讯作者:Schiffer JT
{{
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 }}
Daniel Reeves其他文献
Daniel Reeves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('Daniel Reeves', 18)}}的其他基金
Simulating persistence and elimination of the HIV reservoir
模拟 HIV 病毒库的持续存在和消除
- 批准号:
10083066 - 财政年份:2020
- 资助金额:
$ 12.3万 - 项目类别:
Simulating persistence and elimination of the HIV reservoir
模拟 HIV 病毒库的持续存在和消除
- 批准号:
10593367 - 财政年份:2020
- 资助金额:
$ 12.3万 - 项目类别:
Simulating persistence and elimination of the HIV reservoir
模拟 HIV 病毒库的持续存在和消除
- 批准号:
10226330 - 财政年份:2020
- 资助金额:
$ 12.3万 - 项目类别:
Simulating persistence and elimination of the HIV reservoir
模拟 HIV 病毒库的持续存在和消除
- 批准号:
10447769 - 财政年份:2020
- 资助金额:
$ 12.3万 - 项目类别:
相似海外基金
Toward a Political Theory of Bioethics: Participation, Representation, and Deliberation on Federal Bioethics Advisory Committees
迈向生命伦理学的政治理论:联邦生命伦理学咨询委员会的参与、代表和审议
- 批准号:
0451289 - 财政年份:2005
- 资助金额:
$ 12.3万 - 项目类别:
Standard Grant