Scientist Receives $2.8 Million to Study Critical Cell Signaling Mechanism and Develop Potential Therapeutics

By Eric Sauter

A scientist from the Florida campus of The Scripps Research Institute has been awarded a pair of grants totaling $2.8 million from the National Institute of General Medical Sciences of the National Institutes of Health, and from TargAnox, a Massachusetts-based biotechnology firm.

Kate Carroll, a Scripps Research associate professor, will be the principal investigator for the new projects.

Research funded by both grants will focus on a process known sulfenylation, a relatively new field of research. During periods of cellular stress, caused by factors such as UV radiation or chronic diseases such as cancer, the level of highly reactive oxygen-containing molecules can increase, resulting in inappropriate modification of proteins and cell damage through this process. One oxidant produced naturally in the body, hydrogen peroxide, acts as a messenger that can activate cell proliferation.

In the new research, Carroll will look at cell signaling in sulfenylation and explore ways that it might be modified with potential drug compounds to treat conditions such as lung and breast cancers, as well as be used to diagnose and monitor such diseases.

To explore the process, Carroll and her colleagues have developed a highly selective chemical probe—known as DYn-2— that can detect minute differences in sulfenylation rates within the cell. The new four-year, approximately $1.5 million NIH grant (award number 1R01GM102187-01) will fund work utilizing that chemical probe to fully define the molecular mechanism through which a key signaling protein, epidermal growth factor receptor (EGFR), is modified by hydrogen peroxide.

“The grant from NIH will let us take a closer look at the basic mechanics of the sulfenylation process and detail how oxidation regulates EGFR,” Carroll said. “The TargAnox study uses that work as a spring board into potential treatments.”

Carroll said she also plans to investigate additional targets of sulfenylation and to test various compounds that can reverse the process.

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