# Single Cell Methods for Bioeffector Discovery and Analysis

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2024 · $661,374

## Abstract

PROJECT SUMMARY
Natural product therapeutics remain critically important in the treatment of cancer, with most patients diagnosed
with cancer receiving natural product-based chemotherapy, such as microtubule disrupting agents and DNA
intercalators. Select chemotherapeutic small molecules, the majority of which are natural products, have an
additional therapeutic benefit in their ability to stimulate a productive form of natural immunity against the cancer
cells that they injure or kill. For example, chemically induced damage associated molecular pattern expression
can recruit antigen presenting cells to phagocytose damaged cancer cells and display cancer cell antigens to
prime and activate T cells for adaptive immunity. Notably however, natural product induced anti-tumor immunity
properties of these select compounds were only discovered subsequent to their clinical application. We
hypothesize that the pathways by which such immunogenic natural products injure and kill cancer cells
determines the production of damage associated molecular patterns and ensuing innate and adaptive immune
responses against treated cells. We propose to develop and apply a high throughput, multiplexed, single cell
chemical biology assay platform for the discovery of chemically induced antitumor immunity. Using this system,
we will map the associations between regulated cell death and injury signaling in treated cells to functional
cellular markers of immunogenicity for several classes of known and new natural products. This goal will be
accomplished through three aims: (1) Discover and characterize secondary metabolites via regulated cell death
and injury cytometric phenotypes; (2) Define the relationships between cell injury and death signaling phenotypes
and damage associated molecular patterns, and immunogenic cell signaling in cancer and immune cells; (3)
Validate chemical agents inducing immunogenic cell injury and death via antigen cross priming assays and deep
cellular profiling using flow cytometry. Relevance: The successful completion of the proposed research is
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 positive impact on human health. Furthermore,
the discovery of the multiplexed cell-targeting immuno-oncological structure-activity relationships within newly
discovered compounds and known but not commercially available compound families, may provide new targeted
therapeutics, with greater efficiency and reduced clinical toxicity.

## Key facts

- **NIH application ID:** 10980953
- **Project number:** 2R01CA226833-06A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** BRIAN O BACHMANN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $661,374
- **Award type:** 2
- **Project period:** 2018-12-18 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980953

## Citation

> US National Institutes of Health, RePORTER application 10980953, Single Cell Methods for Bioeffector Discovery and Analysis (2R01CA226833-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10980953. Licensed CC0.

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