Shuichi Takayama, PhD (Department of Biomedical Engineering, Georgia Institute of Technology)
Hang Lu, PhD (School of Chemical & Biomolecular Engineering, Georgia Institute of Technology)
Andrés García, PhD (School of Mechanical Engineering, Georgia Institute of Technology)
Dr. Jocelyn Grunwell (Emory CHOA/Pediatrics)
Dr. Rabindra Tirouvanziam (Emory Pediatrics)
A functional assay of neutrophil recruitment and activation for immunomodulatory drug screening
This project will develop a functional cell-based assay for testing neutrophil-targeted therapeutics. We apply the assay to understand patient-specific differences in response to drugs for pediatric acute respiratory distress syndrome (PARDS). We hypothesize that therapeutics targeting neutrophil activation will elicit heterogeneous responses depending on the patient’s pathobiological features, specifically tracheal aspirate cytokine concentrations. First, we will validate the assay conditions for precise, reliable detection of drug responses. Therefore, we will mitigate sample dilution effects, define a positive control condition, and optimize the timing of each assay step. With these parameters, we will proceed to evaluate 3 immunomodulatory drugs in a trial cohort of 6 patients with severe PARDS: IL-6 receptor antagonist Tocilizumab, IL-1 receptor antagonist Anakinra, and JAK/STAT inhibitor Baricitinib. We expect drug response heterogeneity due to variable patient-specific cytokine profiles in the tracheal aspirate that neutrophils are primed and recruited to during our assay. We will therefore compare the drug response of each patient to the initial concentration of 21 tracheal aspirate cytokines to determine whether drug responses are related to cytokine profiles in our assay. Ultimately, this platform will enable the identification of “likely-responder” patients who couldbe treated with targeted interventions or enrolled in trials for anti-neutrophil therapy.