Kendall Williams
BME PhD Defense Presentation
Date: 2023-11-02
Time: 2:00 PM - 4:00 PM
Location / Meeting Link: EBB CHOA Seminar Room (https://gatech.zoom.us/j/99901813078?pwd=Y2hRNExnd1E1VGEvZzlMSXNYQmxXdz09)
Committee Members:
Wilbur Lam, MD, PhD (Advisor); Andrés García, PhD; Melissa Kemp, PhD; David Myers, PhD; Christopher Porter, PhD
Title: High-efficiency multi-drug functional profiling in a microfluidic device towards personalized predictions in pediatric leukemia
Abstract:
Acute lymphoblastic leukemia is the most common form of pediatric cancer, and while treatment outcomes have improved dramatically over the past several decades for these patients, this same progress has not been achieved for those who experience relapse or refractory disease, particularly in T-ALL. To further improve outcomes for these patients, new strategies need to be devised to both identify patients most at risk of relapse a priori to treatment exposure and optimally match them with emerging new therapeutic options. To that end, in this thesis, we describe the development of an efficient microfluidics-based assay for functional evaluation of candidate drug combinations in pediatric ALL. In Aim 1, we first describe the development and characterization of the system and demonstrate its capabilities using leukemia cell lines. Next, in Aim 2, we evaluate response to standard induction therapy across a set of diagnostic ALL patient samples, and determine the predictive value of the assay through correlation to clinical outcome metrics. Lastly, as a final proof-of-concept, we use the developed and validated system to evaluate an experimental treatment regimen in a set of patients who did not respond well to standard regimens. In sum, the results of this work have provided a new methodology for higher-order combination drug screening in limited sample settings, established the predictive value of combination response profiling in the context of available clinical data, and finally, evaluated an experimental drug combination across a set of samples from clinical non-responders.
