# Linking metabolic activity with drug sensitivity using metabolic influence networks

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $366,446

## Abstract

Project Summary
The impact of cellular metabolism on drug susceptibility has been observed in a wide range of organisms and
cell types. However, how metabolism influences the activity of diverse classes of drugs has not been
systematically explored. Linking metabolism and drug sensitivity has been a challenge due to both the impact
of metabolism on numerous cellular processes, and the complexity of drug response. To address this, a
combination of cutting-edge experimental and computational systems-biology tools will be applied to dissect
the mechanisms by which cellular metabolism impacts the activity of drugs. The overall goal of my lab is to
develop systems biology algorithms to reconstruct metabolic regulation and harness it for drug discovery. Here
we propose to develop a new approach to link metabolism with various cellular process, called the ‘metabolic
influence network’. We will use it to predict the impact of metabolic activity of a cell on drugs that inhibit diverse
cellular processes. This framework will be applied to E. coli, yeast and human cell lines, allowing us to uncover
conserved principles linking metabolism with potency of drugs that target cellular processes such as
replication, transcription or signaling. This approach will be tested experimentally by altering cellular metabolic
state and drug sensitivity with nutrient screens, enzyme inhibitors and drug combinations. Our systems
approach will allow us to quantify the myriad effects of cell metabolism on drug action, including uptake,
collateral interactions, and efflux. Ultimately, this research program can help precision medicine efforts by
matching therapy based on cellular metabolic activity and the in vivo metabolic environment.

## Key facts

- **NIH application ID:** 10408114
- **Project number:** 5R35GM137795-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Sriram Chandrasekaran
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $366,446
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408114

## Citation

> US National Institutes of Health, RePORTER application 10408114, Linking metabolic activity with drug sensitivity using metabolic influence networks (5R35GM137795-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408114. Licensed CC0.

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