Impact of microbiota on AIDS-Kaposi’s sarcoma development and therapy

微生物群对艾滋病-卡波西肉瘤发展和治疗的影响

基本信息

  • 批准号:
    10753890
  • 负责人:
  • 金额:
    $ 79.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-08 至 2028-08-31
  • 项目状态:
    未结题

项目摘要

Project Abstract Microbiota imbalance impacts the development and therapeutic outcome of cancer by altering host immune response and inflammation. Kaposi’s sarcoma (KS) is the most common cancer in HIV-infected patients caused by infection of Kaposi’s sarcoma-associated herpesvirus (KSHV). Despite antiretroviral therapy, KS remains common among HIV-infected patients. It remains unclear what factors might influence the development and therapeutic outcome of AIDS-KS? In response to RFA-CA-22-056 entitled: “Basic/Translational Research on Health Disparities in Underrepresented People Living with HIV (PLWH) and Cancer”, this application specifically addresses the underserved African populations that have high numbers of new HIV infections with the long- term goal is to delineate the pathogenesis of AIDS-associated KS (AIDS-KS), and identify effective therapeutic targets and agents as well as prognostic biomarkers. We have recently shown the impoverishment of oral microbial diversity and enrichment of specific microbiota in oral AIDS-KS, and demonstrated that bacteria and their products lipopolysaccharide and flagellin promote KSHV-induced tumorigenesis by enhancing inflammation in a preclinical KSHV-induced KS animal model. Our hypothesis is that specific microbiota regulates inflammation to impact KS development and therapeutic outcome in AIDS-KS patients. We have assembled a strong collaborative team with diverse expertise in HIV infection, KSHV biology, microbiome, clinical sciences, epidemiology, statistics, computational biology and machine learning. We will take advantage of the long-term clinical studies in Africa with well-defined cross-sectional, case-control and longitudinal cohorts of large HIV-infected and AIDS-KS populations directed by investigators of this project. We will determine the impact of specific microbiota on inflammation and AIDS-KS development by performing case-control analyses in naïve AIDS-KS and HIV/KSHV patients without KS (Aim 1); and examine the impact of specific microbiota on the therapeutic outcome of KS by case-control longitudinal analyses of AIDS-KS patients undergoing anti-retroviral therapy followed by validation analyses in an independent cohort (Aim 2). This interdisciplinary project will analyze the molecular, virological, microbial, immunological, single cell spatial omics, and clinical features of AIDS-KS patients using advanced machine learning approaches. We expect to identify factors that influence the development and therapeutic outcome of AIDS-KS patients. The proposed work is highly significant, and will have prognostic, preventive and therapeutic impacts on AIDS-KS patients. This will be the first time that the role of microbiota will be systematically examined in AIDS-KS patients from well-characterized cohorts. The proposed innovative approaches such as spatial single cell sequencing and machine learning will generate unique and unprecedented results, providing novel insights into the pathogenesis and therapeutic outcome of AIDS-KS.
项目摘要

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)

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Shou-Jiang Gao其他文献

Shou-Jiang Gao的其他文献

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{{ truncateString('Shou-Jiang Gao', 18)}}的其他基金

Citrulline-urea cycle in KSHV cellular transformation
KSHV 细胞转化中的瓜氨酸-尿素循环
  • 批准号:
    10634838
  • 财政年份:
    2023
  • 资助金额:
    $ 79.31万
  • 项目类别:
Regulation of KSHV replication by N6-methyladenosine (m6A) - Diversity Supplement
N6-甲基腺苷 (m6A) 对 KSHV 复制的调节 - Diversity Supplement
  • 批准号:
    10533427
  • 财政年份:
    2022
  • 资助金额:
    $ 79.31万
  • 项目类别:
HISTONE MODIFIERS IN ORAL KSHV INFECTION AND MALIGNANCIES
口腔 KSHV 感染和恶性肿瘤中的组蛋白修饰剂
  • 批准号:
    9756364
  • 财政年份:
    2018
  • 资助金额:
    $ 79.31万
  • 项目类别:
KSHV microRNAs in tumor invasion and angiogenesis
KSHV microRNA 在肿瘤侵袭和血管生成中的作用
  • 批准号:
    9906178
  • 财政年份:
    2017
  • 资助金额:
    $ 79.31万
  • 项目类别:
KSHV microRNAs in tumor invasion and angiogenesis
KSHV microRNA 在肿瘤侵袭和血管生成中的作用
  • 批准号:
    10264784
  • 财政年份:
    2017
  • 资助金额:
    $ 79.31万
  • 项目类别:
KSHV microRNAs in tumor invasion and angiogenesis
KSHV microRNA 在肿瘤侵袭和血管生成中的作用
  • 批准号:
    9243868
  • 财政年份:
    2017
  • 资助金额:
    $ 79.31万
  • 项目类别:
Targeting KSHV malignancies and persistent infection
针对 KSHV 恶性肿瘤和持续感染
  • 批准号:
    8943348
  • 财政年份:
    2015
  • 资助金额:
    $ 79.31万
  • 项目类别:
HISTONE MODIFIERS IN ORAL KSHV INFECTION AND MALIGNANCIES
口腔 KSHV 感染和恶性肿瘤中的组蛋白修饰剂
  • 批准号:
    9257374
  • 财政年份:
    2015
  • 资助金额:
    $ 79.31万
  • 项目类别:
HISTONE MODIFIERS IN ORAL KSHV INFECTION AND MALIGNANCIES
口腔 KSHV 感染和恶性肿瘤中的组蛋白修饰剂
  • 批准号:
    9108377
  • 财政年份:
    2015
  • 资助金额:
    $ 79.31万
  • 项目类别:
KSHV microRNAs in cellular transformation and tumorigenesis
KSHV microRNA 在细胞转化和肿瘤发生中的作用
  • 批准号:
    8728172
  • 财政年份:
    2013
  • 资助金额:
    $ 79.31万
  • 项目类别:

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