Student Presenter(s): Shani Kahan
Faculty Mentor: Roger Yu
School/College: Osteopathic Medicine, Old Westbury

Asthma, a chronic respiratory condition with bronchoconstriction, affects approximately 300 million people worldwide. Current asthma treatments, such as β-agonists and steroids, do not suffice in controlling as many as approximately 38.4% of children and 50% of adult patients with asthma. In this project, a novel mechanism was explored to treat bronchoconstriction. This approach involves modifying airway smooth muscle (ASM) constriction utilizing short phosphatidylinositol 4, 5 bisphosphate (PIP2) binding peptide of Gelsolin. We tested our hypothesis using mouse precision-cut lung slices. Peripheral lung luminal airway diameter change to various constrictive agonists and the effect of the gelsolin peptide were observed using phase-contrast microscopy. Gelsolin peptide caused significant ASM relaxation to pre-existing Gq-coupled agonist MCh-induced constriction, in models representing treatment for clinical asthma attack. Gelsolin peptide pretreatment also attenuated subsequent MCh-induced constriction, suggesting the peptide can be used to prevent asthma attack. Furthermore, when treated with caffeine and ryanodine, to deplete the intracellular calcium stores targeted by IP3, the relaxation effect of the gelsolin peptide was no longer observed. In conclusion, the project findings support the hypotheses that gelsolin peptide attenuates ASM constriction and that the relaxing effect of the peptide is due to its PIP2 binding.