Project Grant R15AI199960

The National Institute of Allergy and Infectious Diseases awarded Pacific University $464,024 on August 13, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct research on ornithine decarboxylase as a therapeutic target in Leishmania parasites.

The research integrates basic discovery with translational potential across three aims. Aim 1 will define the role of elevated polyamine levels in promoting parasite persistence under nutrient starvation by comparing wild-type and polyamine-overproducing strains, analyzing polyamine content, survival rates, and apoptotic markers to establish mechanistic links between polyamine levels and stress resistance. Aim 2 will elucidate how polyamines support mitochondrial function using ornithine decarboxylase and spermidine synthase mutants under polyamine-supplemented and -depleted conditions, assessing ATP and NADH production, electron transport chain activity, and oxidative stress to clarify the role of polyamines in parasite bioenergetics. Aim 3 will evaluate the therapeutic potential of repurposing difluoromethylornithine, an ornithine decarboxylase inhibitor approved for African sleeping sickness, as a novel treatment for leishmaniasis.

The period of performance runs from August 13, 2026, through July 31, 2029. Work is performed in Hillsboro, Oregon. The project responds to leishmaniasis as a neglected tropical disease affecting over 12 million people globally, with existing therapies limited by toxicity, rising drug resistance, and the absence of a vaccine.