# Single Cell Methods for Bioeffector Discovery and Analysis

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2022 · $571,471

## Abstract

PROJECT SUMMARY
It is becoming increasingly apparent that discovering new therapeutics for the treatment of cancer must involve
a consideration of: (A) The interplay between the host immune system and tumors. Cancer cells often have
adapted the ability to evade immune surveillance, either by muted antigenicity or via actively disarming immune
activation via immune checkpoint blockade. (B) The connection between chemotherapeutic interventions and
immunogenicity. It has become apparent that the efficacy of many traditional chemotherapies is dependent upon
enhancing the immunogenicity of cancer cells. Without a functional immune system, cytotoxic small molecules
demonstrate decrease selectivity for cancer cells versus healthy ones. (C) The highly heterogeneous nature of
tumors in their native environments. Tumors are comprised of a complex mixture of multiple tumor lineages
embedded host tissue microenvironments. The structure and complexity of the tumor microenvironment has a
direct bearing on the efficacy of therapeutic interventions. This proposal develops a new methodology for
natural product discovery using biopsied human tumors and tumor infiltrating immune cells. Multiplexed
activity metabolomics (MAM) merges flow cytometric microtiter well and bioassay multiplexing with metabolomics
and cheminformatics software to radically accelerate bioactive compound discovery, and specifically addresses
the above considerations in the context of the discovery of acute myeloid leukemia anticancer lead discovery.
Additionally, experimental designs will provide new insights into the effect and mechanism of a reference set of
known synthetic and natural small molecules, providing a basis set of cellular responses to cytotoxic small
molecules for the evaluation of lead compounds generated during discovery efforts. Specific aims of this proposal
are organized independently to develop a multiplexing system for bioeffector discovery, a multiplexing system
for analysis of heterogeneous cell mixtures, and a deep cell response profiling via multiplexed immunoassay of
markers of cell status. Aims circumscribe this plan for our cross-disciplinary team employing metabolomics,
natural product chemical biology, and discovery (Bachmann), cytometry and cancer biology (Irish), and clinical
cancer biology (Ferrell). We aim to: (1) Identify microbial metabolites that specifically target human cancer cells
from primary tumor tissue samples to modulate anti-tumor immunity. (2) Discover metabolites that remodel
immune cell population fates to enhance anti-tumor immunity, (3) Determine deep single cell metabolite
responses of malignant and tumor-associated immune cells using known, clinically active molecules as reference
points Relevance: This successful completion of the proposed research is highly relevant to human health
because it will provide methods to accelerate the identification of potential anticancer natural products, which
have had and continue to have a large impac...

## Key facts

- **NIH application ID:** 10329957
- **Project number:** 5R01CA226833-04
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** BRIAN O BACHMANN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $571,471
- **Award type:** 5
- **Project period:** 2018-12-18 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10329957

## Citation

> US National Institutes of Health, RePORTER application 10329957, Single Cell Methods for Bioeffector Discovery and Analysis (5R01CA226833-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10329957. Licensed CC0.

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