# Chemical Tools to Study the Role of Biological Aldehydes

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $375,496

## Abstract

Project Summary/Abstract: Jefferson Chan, Ph.D.
The aberrant production of low molecular weight aldehydes (i.e., formaldehyde and acetaldehyde)
and lipid-derived aldehydes (e.g., 4-hydroxynonenal) have a major influence on the aging of stem
cells. Molecular level changes that result from aldehyde-mediated epigenetic modifications,
oxidative DNA damage and DNA cross-linking can lead to a variety of human diseases including
autoimmune diseases, cancer, diabetes, and neurological disorders. However, our general
understanding of the mechanistic underpinnings is insufficient owing to a dearth of methods to
non-invasively detect reactive aldehydes, manipulate their subcellular concentrations, as well as
to monitor the activity of aldehyde processing enzymes. The projects described in this application
aim to address each of these three areas of research through the development of new chemical
tools. Specifically, we will draw from our established expertise in molecular imaging and probe
design to develop fluorescent and photoacoustic probes to non-invasively visualize endogenous
aldehydes at the cellular and whole animal levels, respectively. We will complement this work by
developing new aldehyde donors that can be employed to deliver a specific aldehyde species on
demand using light. Since light can be focused with high precision onto small volumes within a
cell, the delivery of a given reactive aldehyde can be achieved with unprecedented spatiotemporal
control. Lastly, we will develop new fluorescent substrates to monitor the enzymatic activity of
aldehyde processing enzymes implicated to play a crucial role in mediating stem cell plasticity.
This work will be based on recent studies from our group where we have successfully developed
a new probe to detect stem cells via elevated aldehyde dehydrogenase 1A1 activity. The
integrated approach in this proposed research spanning chemical synthesis to molecular imaging
offers an exciting opportunity to study the biology of reactive aldehyde species related to aging
and associated disease states.

## Key facts

- **NIH application ID:** 9968294
- **Project number:** 5R35GM133581-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Jefferson Chan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,496
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968294

## Citation

> US National Institutes of Health, RePORTER application 9968294, Chemical Tools to Study the Role of Biological Aldehydes (5R35GM133581-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9968294. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*