Development of Chemical Tools to Study How Stem Cells Age
The aberrant production of highly reactive aldehydes can have a major influence on the aging of stem cells. Molecular level changes that result from aldehydes include important alteration to DNA and this can lead to a variety of human diseases including autoimmune diseases, cancer, diabetes, and neurological disorders. Unfortunately, our general understanding of the mechanisms involved are 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.
Professor Chan plans to address each of these three areas of research through the development of new chemical tools. He will draw from his established expertise in molecular imaging and probe design to develop fluorescent and photoacoustic probes to non-invasively visualize the abnormal production of aldehydes at the cellular and whole animal levels, respectively. He will complement this work by developing new aldehyde donor molecules 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 control over the location and time of delivery. Lastly, he will develop new fluorescent substrates to monitor the enzymatic activity of aldehyde processing enzymes implicated to play a crucial role in mediating the aging of stem cells. 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.