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

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $784,127

## Abstract

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 pathogenes...

## Key facts

- **NIH application ID:** 10925307
- **Project number:** 5R01CA284554-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Shou-Jiang Gao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $784,127
- **Award type:** 5
- **Project period:** 2023-09-08 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10925307

## Citation

> US National Institutes of Health, RePORTER application 10925307, Impact of microbiota on AIDS-Kaposi’s sarcoma development and therapy (5R01CA284554-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10925307. Licensed CC0.

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