Shivani Vyas
BME PhD Defense Presentation

Date: 2025-11-21
Time: 1:30 PM - 3:30 PM
Location / Meeting Link: Kendeda Building Room 230 / https://gatech.zoom.us/j/91652549488?pwd=AAkSlVlRL6acpc7xyfDSbBDYyYsSwu.1&from=addon

Committee Members:
Krishnendu Roy (Advisor); Jyothi Rengarajan; Shuichi Takayama; Leslie Chan; Jason Cook


Title: Engineering the Immune Dysregulation of the Pulmonary Microenvironment in Acute Respiratory Distress Syndrome and Tuberculosis

Abstract:
Acute respiratory distress syndrome (ARDS) and tuberculosis (TB) represent distinct yet interconnected forms of pulmonary immune dysregulation in which inflammatory and suppressive myeloid responses contribute to tissue damage and impaired immune resolution. Myeloid-derived suppressor cells (MDSCs) are central mediators of this imbalance, promoting chronic inflammation and immunosuppression. However, current strategies to target MDSCs lack specificity and often produce systemic off-target effects. To address this limitation, this work focuses on developing and optimizing synthetic nanoparticle antibodies (SNAbs), which are multivalent bifunctional gold nanoparticles engineered to selectively deplete MDSCs. The SNAb platform was refined to enable scalable synthesis and functionalization with MDSC-targeting synthetic peptides specific for S100A8/A9, CD124, and CD206 receptors. An aerosol-induced murine model of ARDS was established with lipopolysaccharides (LPS) and lipoarabinomannan (LAM), allowing for the precise induction of acute lung injury and characterization of MDSC recruitment kinetics. SNAbs were evaluated in vitro using mouse ARDS lung cells and human-expanded MDSCs, demonstrating selective targeting and depletion of immunosuppressive subsets. In vivo studies in murine models of ARDS and TB further confirmed MDSC depletion and immune rebalancing following pulmonary administration of SNAbs. Collectively, this work establishes SNAbs as a versatile immunotherapeutic platform capable of restoring immune homeostasis and mitigating inflammation in both acute and chronic pulmonary diseases. SNAbs represent a potent strategy to restore immune balance and mitigate dysregulation across diverse disease contexts.