Katherine Nguyen
BME PhD Defense Presentation
Date: 2024-12-20
Time: 2:30 PM - 4:30 PM
Location / Meeting Link: IBB Suddath Seminar Room 1128; https://gatech.zoom.us/j/93010660290?pwd=S5ivaaKmhwTU4P6CoMPHLnipGkS8lD.1
Committee Members:
Shuichi Takayama, PhD (Advisor) Rebecca Levit, MD Jason Knight, MD, PhD Aniruddh Sarkar, PhD Wilbur Lam, MD, PhD
Title: USING MIMETIC NEUTROPHIL EXTRACELLULAR TRAPS (NETS) AS A TOOL TO ELUCIDATE THE ROLE OF NETS IN NEUTROPHIL FUNCTION AND DYSFUNCTION
Abstract:
Neutrophils are the immune system's first responders, able to quickly move around the body and respond to infection. One of their methods to protect the body is to release neutrophil extracellular traps (NETs). NETs are primarily composed of DNA, histones, and neutrophil granule proteins. NETs have been shown to be able to trap and kill bacteria and modulate inflammation. However, NETs are a double-edged sword, as their over-production or inefficient clearance is linked to various diseases including cardiovascular, autoimmune, pulmonary, and cancer due to excessive cell damage, inflammation, and other complications. Because of this, there is growing interest in developing therapeutics targeting NETs. However, current tools and methods used in NET research faces challenges that limit the rate of research. NETs are highly variable in stimulation methods, structure, and functional components making it difficult to control experimental variables. Furthermore, in vitro NET studies are difficult to accomplish at scale with the current resource cost and NET yield produced from neutrophils. In this thesis, I develop and utilize engineered, mimetic NETs as new tools to conduct and advance NET research. In Aim 1, I use mimetic NETs to create a simplified, scalable, low cost, high-throughput, lower variability, shelf-stable, and transportable assay that performs functionally the same as current in vitro NET degradation assays. In Aim 2, I use mimetic NETs to see the impact of NETs on neutrophil transmigration through a NET damaged lung. Aim 3 builds upon Aim 1 to create the first NET degradation assay where protein degradation is observable. The work in this thesis provides assays and models that have improved reproducibility, high throughput, and have precise control over NET composition and concentration for future studies in potential NET based therapeutics and research in the role of NETs in physiology.