Human pluripotent stem cell-based assessment of dolutegravir teratogenicity

基于人类多能干细胞的多替拉韦致畸性评估

基本信息

  • 批准号:
    10231131
  • 负责人:
  • 金额:
    $ 7.8万
  • 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:
    2020-08-10 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

Proposal Abstract In 2018, the Food and Drug Administration issued a warning about pregnancy risk of dolutegravir, an antiretroviral medication to treat human immunodeficiency virus (HIV). This warning was based on an NIH- funded observational study in Botswana, which found a significantly higher incidence of severe neural tube defects in babies born to women who received dolutegravir before pregnancy or early in the first trimester. Nevertheless, the World Health Organization (WHO) announced in 2019 that it still recommends dolutegravir as preferred HIV treatment for all populations, including women of reproductive age. WHO's decision is based on additional observational studies, suggesting that in spite of statistically higher incidence, the overall teratogenic risk of dolutegravir is relatively small and is outweighed by the benefit as an effective anti-HIV medication. However, it is currently unclear what mechanisms are involved in the action of dolutegravir to induce neural tube defects and what circumstances may exacerbate the teratogenic effects of dolutegravir. Such mechanistic understanding is essential for further studies to anticipate what types of patients are at risk from adverse impact of dolutegravir. The goal of the proposed project is to investigate the teratogenic potential of dolutegravir, using the novel assay platform of human embryonic stem cells that my lab established. Specifically, we will (1) characterize molecular impact of dolutegravir in human pluripotent stem cell aggregates, (2) determine whether dolutegravir causes teratogenic effects through folic acid antagonism, and (3) investigate synergistic effects between dolutegravir and other anti-HIV medications. Mechanistic insights obtained from the proposed experiments should help further investigations and endeavors to minimize potential teratogenic risks from dolutegravir exposures.
建议文摘

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Developmental toxicity of remdesivir, an anti-COVID-19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells.
  • DOI:
    10.1002/bdr2.2111
  • 发表时间:
    2023-01-15
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    Kirkwood-Johnson, Lauren;Marikawa, Yusuke
  • 通讯作者:
    Marikawa, Yusuke
Toward better assessments of developmental toxicity using stem cell-based in vitro embryogenesis models.
  • DOI:
    10.1002/bdr2.1984
  • 发表时间:
    2022-10-01
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    Marikawa, Yusuke
  • 通讯作者:
    Marikawa, Yusuke
Gastruloids: Pluripotent stem cell models of mammalian gastrulation and embryo engineering.
  • DOI:
    10.1016/j.ydbio.2022.05.002
  • 发表时间:
    2022-08
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Arias, Alfonso Martinez;Marikawa, Yusuke;Moris, Naomi
  • 通讯作者:
    Moris, Naomi
Remdesivir impairs mouse preimplantation embryo development at therapeutic concentrations.
  • DOI:
    10.1016/j.reprotox.2022.05.012
  • 发表时间:
    2022-08
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Marikawa, Yusuke;Alarcon, Vernadeth B.
  • 通讯作者:
    Alarcon, Vernadeth B.
{{ 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 }}

YUSUKE MARIKAWA其他文献

YUSUKE MARIKAWA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('YUSUKE MARIKAWA', 18)}}的其他基金

Teratogenicity assessment of new antiviral drugs using 3D morphogenesis models
使用 3D 形态发生模型评估新型抗病毒药物的致畸性
  • 批准号:
    10741474
  • 财政年份:
    2023
  • 资助金额:
    $ 7.8万
  • 项目类别:
Human pluripotent stem cell-based assessment of dolutegravir teratogenicity
基于人类多能干细胞的多替拉韦致畸性评估
  • 批准号:
    10043778
  • 财政年份:
    2020
  • 资助金额:
    $ 7.8万
  • 项目类别:
Regeneration of meiotic spindle during oocyte vitrification
卵母细胞玻璃化冷冻过程中减数分裂纺锤体的再生
  • 批准号:
    8242474
  • 财政年份:
    2012
  • 资助金额:
    $ 7.8万
  • 项目类别:
Regeneration of meiotic spindle during oocyte vitrification
卵母细胞玻璃化冷冻过程中减数分裂纺锤体的再生
  • 批准号:
    8518432
  • 财政年份:
    2012
  • 资助金额:
    $ 7.8万
  • 项目类别:
MOLECULAR NATURE OF PLURIPOTENT STEM CELLS
多能干细胞的分子性质
  • 批准号:
    6972106
  • 财政年份:
    2004
  • 资助金额:
    $ 7.8万
  • 项目类别:
Body Plan Formation in Early Mouse Embryo
早期小鼠胚胎的身体计划形成
  • 批准号:
    6638010
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:
Body Plan Formation in Early Mouse Embryo
早期小鼠胚胎的身体计划形成
  • 批准号:
    6744094
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:
Body Plan Formation in Early Mouse Embryo
早期小鼠胚胎的身体计划形成
  • 批准号:
    6536304
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:
Body Plan Formation in Early Mouse Embryo
早期小鼠胚胎的身体计划形成
  • 批准号:
    6316426
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:

相似海外基金

Hormone therapy, age of menopause, previous parity, and APOE genotype affect cognition in aging humans.
激素治疗、绝经年龄、既往产次和 APOE 基因型会影响老年人的认知。
  • 批准号:
    495182
  • 财政年份:
    2023
  • 资助金额:
    $ 7.8万
  • 项目类别:
Investigating how alternative splicing processes affect cartilage biology from development to old age
研究选择性剪接过程如何影响从发育到老年的软骨生物学
  • 批准号:
    2601817
  • 财政年份:
    2021
  • 资助金额:
    $ 7.8万
  • 项目类别:
    Studentship
RAPID: Coronavirus Risk Communication: How Age and Communication Format Affect Risk Perception and Behaviors
RAPID:冠状病毒风险沟通:年龄和沟通方式如何影响风险认知和行为
  • 批准号:
    2029039
  • 财政年份:
    2020
  • 资助金额:
    $ 7.8万
  • 项目类别:
    Standard Grant
Neighborhood and Parent Variables Affect Low-Income Preschool Age Child Physical Activity
社区和家长变量影响低收入学龄前儿童的身体活动
  • 批准号:
    9888417
  • 财政年份:
    2019
  • 资助金额:
    $ 7.8万
  • 项目类别:
The affect of Age related hearing loss for cognitive function
年龄相关性听力损失对认知功能的影响
  • 批准号:
    17K11318
  • 财政年份:
    2017
  • 资助金额:
    $ 7.8万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9320090
  • 财政年份:
    2017
  • 资助金额:
    $ 7.8万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    10166936
  • 财政年份:
    2017
  • 资助金额:
    $ 7.8万
  • 项目类别:
Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology
影响调节和 β 淀粉样蛋白:衰老和年龄相关病理学中的成熟因素
  • 批准号:
    9761593
  • 财政年份:
    2017
  • 资助金额:
    $ 7.8万
  • 项目类别:
How age dependent molecular changes in T follicular helper cells affect their function
滤泡辅助 T 细胞的年龄依赖性分子变化如何影响其功能
  • 批准号:
    BB/M50306X/1
  • 财政年份:
    2014
  • 资助金额:
    $ 7.8万
  • 项目类别:
    Training Grant
Inflamm-aging: What do we know about the effect of inflammation on HIV treatment and disease as we age, and how does this affect our search for a Cure?
炎症衰老:随着年龄的增长,我们对炎症对艾滋病毒治疗和疾病的影响了解多少?这对我们寻找治愈方法有何影响?
  • 批准号:
    288272
  • 财政年份:
    2013
  • 资助金额:
    $ 7.8万
  • 项目类别:
    Miscellaneous Programs
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了