At WashU, I’ve had the incredible opportunity to engage in exciting research beyond the classroom with Dr. Jennifer Alexander-Brett and the JAB Lab. Starting in my freshman spring semester, I’ve taken a deep dive into respiratory immunobiology and protein biochemistry. Our group studies how the airway epithelium, the living linings of our lungs, acts as an active immune sensor. Central to this investigation is IL-33, a cytokine released by damaged epithelium that drives the persistent inflammation underlying asthma and chronic obstructive pulmonary disease (COPD).

For years, IL-33 was believed to act through a single receptor, ST2. However, an alternative pathway has been identified for oxidized IL-33 to signal through the receptor for advanced glycation end-products (RAGE), driving the weakened defenses and excess mucus seen in COPD. Understanding this interaction requires characterizing the different affinities, partners, and actual IL-33/RAGE complex. My primary involvement has been building the system to solve the structure, all the way from cloning the genes for IL-33 and RAGE, to expressing, purifying, and validating the proteins with chromatography and Western blots to eventually build a 3D structure. I’ve tested the pathway with ELISAs and cell-reporter assays to show how different RAGE isoforms and IL-33 oxidation states alter receptor specificity. By defining how IL-33 signaling output changes, we’ll be able to better clarify IL-33 biology to mediate the pathway and inform future anti-inflammatory therapies.

My time in the JAB Lab has fundamentally shaped who I am as a student and scientist. I’ve learned countless bench techniques and skills, but more importantly, working on a longitudinal project where the answer genuinely isn’t known has challenged me to reframe how I approach problems. I’ve learned to actively engage setbacks and think critically about experimental design, bolstering my love for science. Research isn’t straightforward; I’m always learning more, and that’s what makes it so incredibly exciting. I’m grateful for the amazing mentorship and support of the JAB Lab, and for the immense growth I’ve experienced through Bio 4950.