Chemical Probes for Studying Stem Cells and Environmental Interactions in Aging

Project Summary / Abstract Stem cells are critical cell populations that maintain tissue health and regenerative capacity. Understanding the mechanisms leading to the decline of stem cell function can provide unique insights into how their regenerative abilities can be enhanced and prolonged to facilitate healthy aging. The environment in which stem cells reside has a major impact on their function, with factors such as oxygen availability, inflammation, oxidative stress, and the presence of reactive aldehydes playing crucial roles. However, our understanding of these mechanisms is limited due to a lack of methods to non-invasively detect these biomarkers within native tissue environments with the requisite sensitivity and accuracy. Likewise, tracking stem cells in vivo without altering them represents another long-standing challenge. This renewal application aims to address these gaps through the development of innovative chemical biology tools. We will continue to leverage our expertise in molecular imaging and probe design to develop advanced and sensitive probes for non-invasive visualization of these key biomarkers, as well as the activity of aldehyde-processing enzymes which can be used as a proxy for stem cell detection at the cellular and whole-animal levels. Additionally, we will develop dual- functional probes to study the crosstalk between stem cells and their tissue environment, focusing on oxygen availability, inflammation, and other biomarkers that influence stem cell function and aging. Our approach offers an exciting opportunity to significantly advance our understanding of this fundamental life process and identify novel therapeutic targets to promote healthy aging.