BME PhD Dissertation Defense - Steve Wang
- Starts: 10:00 am on Monday, August 14, 2017
Title: "1-D IMAGING CYTOMETRY: STATISTICAL ASSAYS FOR IMMUNOTHERAPY DRUG SCREENING" Committee: Daniel Ehrlich, BME (Advisor) Sandor Vajda, BME (Chair) Wilson Wong, BME Darren Roblyer, BME Adrian Whitty, Chemistry Abstract: Modern cancer immunotherapy involves the conditioning of endogenous T cells to fight cancerous bodies that have managed to resist or avoid detection. Recently approved antibody drugs target the immune checkpoint pathway in T cells to prevent their tolerance to cancer antigens. There exists a compelling need, especially in the drug discovery world, to develop better assays for screening and to study the underlying mechanisms of these new antibody drugs. The core motivation of my work is to develop a primary cell assay for the immune checkpoint pathway using 1-D imaging cytometry. The assay is focused on high throughput and high content screening. It takes advantage of our novel 1-D imaging cytometer platform. The assay is designed to artificially induce anergy in primary human T cells and systemically study their drug response. An automated statistical method quantifies the functional phenotypes of both healthy and anergic T cells into a single descriptive readout. Reducing localization of biomarkers into a single ‘activity score’ readout has many advantages for drug screening and characterization. Our 1-D instrument leverages both the high throughput aspects of traditional flow cytometry and the high spatial content of 2-D imaging cytometers. Preliminary assays were also developed to study T cell activation dynamics and other phases of the immune checkpoint pathway. All of these assays help validate the 1-D imaging platform and showcase its potential for large-scale drug screening applications. We demonstrate that 1-D imaging provides many advantages for rapid development of primary T cell assays in flow.
- 44 Cummington Mall, room 401