DOI

https://doi.org/10.25772/BG79-S858

Author ORCID Identifier

0000-0002-6503-9294

Defense Date

2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Nanoscience and Nanotechnology

First Advisor

Jason Reed, PhD

Second Advisor

Joshua Harrell, PhD

Third Advisor

Loren Picco, PhD

Fourth Advisor

Amir Toor, MD

Fifth Advisor

Ross Mikkelsen, PhD

Abstract

Single cell mass is tightly regulated throughout generations and the cell cycle, making it an important marker of cell health. Abnormal changes in cell size can be the first indication of dysfunction in response to environmental stimuli such as cytotoxic drugs. Described here is the further development of high-speed live cell interferometry (HSLCI) to concurrently measure the changes in single cell mass of thousands of cells over time. Critically, the high-throughput nature of HSLCI provides realistic pictures of tumor heterogeneity. This throughput enabled HSLCI to correctly predict in vivo carboplatin sensitivity of three triple negative breast cancer patient derived xenografts, while also characterizing the spectrum of drug response from apoptosis to senescence to drug resistance. HSLCI quantified previous qualitative observations of increases in cell size and losses in cell density in senescent cells, and importantly observed proliferative recovery in cells demonstrating thee senescent characteristics. Furthermore, the addition of a micropipette system has enabled the isolation of rare (~1%) drug resistant cells for further study with molecular biology methods. Together, this work highlights HSLCI’s versatility and potential for clinical, translational, and basic research.

Rights

© Graeme Murray

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

7-5-2021

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