# Targeting microbial triggers of gammopathy for immunoprevention

> **NIH NIH UG3** · EMORY UNIVERSITY · 2024 · $789,579

## Abstract

Abstract:
Multiple myeloma (MM) is an incurable plasma cell tumor preceded by a defined preneoplastic
state termed as monoclonal gammopathy of undetermined significance (MGUS). Strategies to
effectively intercept/prevent clinical malignancy remain an unmet need and are the focus of this
application. Changes in microbial communities have been extensively studied in the context of
cancer outcomes and therapy. However, very few causal relationships between specific microbes
and human malignancies have been defined, and suitable models to study these interactions are
lacking. It is increasingly appreciated that MM/MGUS originate in the setting of prior chronic
inflammation and B cell activation, but the underlying triggers remain unknown. This application
involves three PIs (Dhodapkar, Flavell, Palm) with complementary expertise and a track record
of productive collaboration. The application is based on exciting preliminary data describing the
discovery of a commensal microbial species that directly engage several human MM-associated
B-cell receptors. This is supported by data from new humanized models to study interactions
between the human immune system and microbial communities in vivo. The proposal also utilizes
biospecimens from MGUS patients treated with a short course of antibiotics to reduce pathogenic
bacteria. Studies proposed in this application will characterize the full spectrum of human gut
microbes that can potentially serve as antigenic triggers for human B cells and MGUS. It will also
evaluate causal relationships between specific microbes and activation of human B cells as well
as MGUS cells utilizing newly developed models. Finally, it will evaluate how microbial
manipulation in MGUS patients can impact the inflammatory microenvironment known to be
present and implicated in the pathogenesis of MGUS and its transition to clinical malignancy.
Together, these studies may lead to novel approaches for immune-prevention of clinical MM by
targeting the underlying precursor states such as MGUS. Insights from these studies may also
have implications for interactions between specific microbes and human B cells, broadly
impacting human autoimmunity and cancer immunotherapy.

## Key facts

- **NIH application ID:** 10877434
- **Project number:** 1UG3CA290302-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** MADHAV V DHODAPKAR
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $789,579
- **Award type:** 1
- **Project period:** 2024-06-13 → 2025-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877434

## Citation

> US National Institutes of Health, RePORTER application 10877434, Targeting microbial triggers of gammopathy for immunoprevention (1UG3CA290302-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10877434. Licensed CC0.

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