Date of Award

Spring 3-25-2025

Document Type

Honors Thesis

Department/Major

Basic Biomedical Science

Additional Department

Chemistry

First Advisor

William C.W. Chen

Second Advisor

Xuejun Wang

Third Advisor

Jacob Kerby

Keywords

myocardial infarction, inflammation, oxidation, synthetic biomarker system, genetic sensor

Subject Categories

Analytical, Diagnostic and Therapeutic Techniques and Equipment | Cardiovascular System

Abstract

Every year, thousands of Americans suffer from the event of a heart attack, i.e., myocardial infarction (MI). Currently, the early detection of MI remains a challenge. We intend to solve the problem by constructing a synthetic biomarker system that would be able to recognize early warning signs of MI, such as cellular inflammation and oxidative stress. We have proposed two different pathology specific genetic sensors that act as artificial promoters to transcribe a peptide that can be secreted into the blood stream and eventually work its way into the urine and act as a reporter that can be detected through an antibody-based assay.

The first sensor will utilize nuclear factor kappa B (NFB) response elements that quickly respond to inflammation. During the early stages of MI, myocardial cells release NFB which our sensor will detect and subsequently activate the transcription of our small synthetic reporter peptide. The second sensor will utilize nuclear factor-erythroid factor 2-related factor 2 (Nrf2) response elements to oxidative stress. This sensor will detect Nrf2, expressed within myocardial cells, and subsequently promote transcription of our reporter peptide. The reporter peptide, expressed and secreted by myocardial cells under stress, will not interfere with the normal functions of the human body and will be small enough to be filtered through the kidneys to be excreted into the urine for detection. To analyze the effectiveness of our synthetic biomarker systems, we will use a rat H9c2 cardio myoblast model. Withing twenty-four hours, we will detect the reporter peptide present in the culture supernatants with an antibody-based anti-His-tag assay.

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