Author ORCID Identifier

https://orcid.org/0000-0001-8376-2622

Semester

Fall

Date of Graduation

2024

Document Type

Dissertation

Degree Type

PhD

College

School of Public Health

Department

Occupational & Environmental Health Sciences

Committee Chair

Weimin Gao

Committee Co-Chair

Mark Olfert

Committee Member

Michael McCawley

Committee Member

Travis Knuckles

Abstract

Abstract

E-Cigarette (e-cig) use has become widespread in the United States, gaining popularity across various demographics. Despite originally being designed and marketed as a harm-reduction tool for traditional tobacco users who intend to reduce or quit smoking, their use has extended beyond this initial purpose. It is an emerging public health issue for workers who are occupationally exposed to silica and use e-cigs as a "modified risk" product for smoking cessation. This is due to the potential synergistic pathways of pulmonary pathogenesis between e-cig use and silicosis remain unexplored. Further, co-exposure to e-cigs and silica may cause greater damage to the pulmonary parenchyma, potentially resulting in more severe pathophysiological and molecular impairments than those caused by either e-cig use or silica exposure individually. Another gap also exists in strategies to provide relief from harm to the lung following co-exposure to e-cigs and silica. Natural products, such as caffeic acid phenethyl ester (CAPE), have proven to be effective chemopreventive agents for lung disease through regulation of inflammatory and epithelial-mesenchymal transition-related pathways. Our published work suggests that CAPE improves targeted cancer therapies by regulating genes involved in cell cycle arrest and apoptosis. Thus, the overall goal of this project is to elucidate the molecular mechanisms by which CAPE may attenuate the toxic effects of e-cig and silica co-exposure using both a mouse and co-culture cell model.

The first objective of this study is to assess the pathophysiological, biochemical, and molecular effects of combined exposure to e-cigs and/or silica using both a mouse and co-culture cell model. The second objective is to evaluate the chemoprophylactic potential of CAPE to ameliorate pulmonary toxicity induced by e-cig and/or silica in both a mouse and co- culture cell model.

The hypothesis is that 1) that e-cig and/or silica co-exposure employs synergistic molecular mechanisms which result in the development of pulmonary toxicity; and 2) CAPE can be used as a chemoprophylactic agent to mitigate e-cig and silica- induced pulmonary toxicity in complex in vivo and in vitro systems.

The specific aims are to 1): determine the potential of CAPE chemoprophylaxis to prevent e-cig and silica induced lung pathogenesis in vivo. 2) evaluate the protective effects of CAPE following exposure to e-cig and/or silica in a co- culture cell model.

This study addresses the growing public health concern by providing data on the consequences of occupational exposure to silica and e-cig use, as well as exploring the potential of CAPE as a chemoprophylactic agent to mitigate these adverse effects.

Available for download on Saturday, December 13, 2025

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