Date Approved

1-10-2024

Embargo Period

1-10-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Chemical Engineering

College

Henry M. Rowan College of Engineering

Advisor

Kirti Yenkie, Ph.D.

Committee Member 1

Gary Thompson, Ph.D.

Committee Member 2

Benjamin Carone, Ph.D.

Committee Member 3

Sebastian Vega, Ph.D.

Committee Member 4

Rachel Riley, Ph.D.

Keywords

cancer, Cell death, Histone Deacetylase (HDAC), kinases;phosphatases, pulsed electric field

Subject(s)

Cancer--Treatment

Disciplines

Biomedical Engineering and Bioengineering | Chemical Engineering

Abstract

Epigenetic modifications, arising from sub-cellular shifts in histone deacetylase (HDAC) activity and localization, present promising strategies for diverse cancer treatments. HDACs, enzymes responsible for post-translational histone modifications, induce these epigenetic changes by removing acetyl groups from ε-N-acetyl-lysine residues on histones, thereby suppressing gene transcription. Within the HDAC group, class IIa HDACs are notable for their responsiveness to extracellular signals, bridging the gap between external stimuli, plasma membrane, and genome through nuclear-cytoplasmic translocation. This localization offers two significant mechanisms for cancer treatment: nuclear accumulation of HDACs represses oncogenic transcription factors, such as myocyte-specific enhancer factor 2C (MEF2C), triggering various cell death pathways. Conversely, cytoplasmic HDAC accumulation acts similarly to HDAC inhibitors by silencing genes. My dissertation introduces an innovative approach for glioblastoma and breast cancer treatment by investigating the application of microsecond pulsed electric fields. It particularly focuses on HDAC4, a class IIa HDAC overexpressed in these cancers. Beyond demonstrating HDAC4 translocation, my research delves into the intricate roles of kinases and phosphatases, shedding light on the underlying factors governing HDAC4 translocation.

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