The National Institute of General Medical Sciences (NIGMS) has awarded a five-year, $742,500 Project Grant (CFDA 93.859 - Biomedical Research and Research Training) to the University of Alabama at Birmingham (UAB) to conduct research on the formation, metabolism, and cellular signaling actions of tryptophan catabolism-derived electrophiles. The research aims to characterize the mechanisms regulating the production of these bioactive electrophiles from the kynurenine pathway, identify the enzymes involved in their conjugation and inactivation, and assess the impact of these electrophiles on cellular and tissue bioenergetic metabolism. The project will leverage untargeted and targeted mass spectrometry techniques, stable isotope labeling, spatial transcriptomics, and click chemistry to elucidate the multifaceted roles of tryptophan-derived electrophiles in health and disease. The findings from this research have the potential to transform the understanding of tryptophan biology and inform the development of novel clinical approaches for conditions involving dysregulated tryptophan metabolism.
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