Computational Models of the Cardiomyocyte Cell Cycle and Regulation by the DREAM Complex; Presenting the Body Mass Index Through a Data Feminism Lens

Zhao, Catherine, School of Engineering and Applied Science, University of Virginia
Ferguson, Sean, EN-Engineering and Society, University of Virginia

Approximately every 39 seconds an American will experience a heart attack or myocardial infarction (MI). Cardiomyocytes are the cells responsible for contracting the myocardium and generating cardiac output. After MI, there is a progressive death of cardiomyocytes without a counteracting force of sufficient renewal. A pressing issue in the field of cardiology is to identify strategies that enhance adult cardiomyocyte renewal. Therefore, therapeutic strategies that can target cardiac regeneration are considered the holy grail for cardiologists and pharmaceutical companies.

Any MI patient treated within the U.S. healthcare system could be informed of their BMI. However, with the current use of this metric, physicians are contributing to a trend of increased medicalization that has overtaken the traditional physician-patient interaction and reduced the quality of care. By working towards novel computational modeling tools to improve MI treatment and exploring the ways in which data contextualization can challenge the societal narratives surrounding BMI, we can move towards engineering better therapies and solutions for our society.

The DREAM complex plays an important role in the cell cycle by coordinating gene repression during G0 and periodic gene expression, especially during G1/S and G2/M transitions. While it is known that neonatal cardiomyocytes can undergo regeneration, recently the field of cardiology found that adult cardiomyocytes also have regenerative capabilities. Thus, the DREAM complex holds great therapeutic potential post-MI. For my Capstone, a computational model of the DREAM complex signaling pathway was built and validated using over 30 cardiomyocyte and cancer cell experiments from literature. Four simulations demonstrated increased proliferation: DYRK1A knockout and overexpression of B-Myb, Cyclin D/Cdk4, and Cyclin E/Cdk2. We also developed a cardiomyocyte cell cycle model to better understand the dynamics of cardiomyocyte proliferation. The next step is to combine the models in order to provide a framework to unravel the interplays between various regulators of cardiomyocyte renewal and serve as diagnostic tools that can propel future research.

For my STS research project, I examine how we can recontextualize BMI, since according to D'Ignazio and Klein (2020), data must be examined alongside its context to realize the differentials of power and the misaligned collection incentives. We must strip the BMI of its status as an objective metric in order to reclassify it as a holistic measure of individual health relative to weight. I brought together existing post-structural and material feminism critical literature and published research that looks at the material consequences of the BMI on the body. These critiques explore the gendered and socio-economic disparities that BMI perpetuates to better understand the context surrounding BMI, such that we can identify the harm that can accompany BMI with its current use. I examine how health care professionals and patients alike can work together to challenge the use of BMI data sans contextualization, ensure that it is always presented alongside its context so it is not misunderstood, and propose an epistemological shift towards a more holistic approach to BMI as a measure of health.

BS (Bachelor of Science)
BMI, data feminism, post-structural feminism, cardiomyocytes, cardiac regeneration, cell cycle, DREAM complex, computational modeling, logic-based ordinary differential equations, systems pharmacology

STS Advisor: Sean M. Ferguson
Technical Advisors: Jeffrey J. Saucerman; Bryana N. Harris
Technical Team Members: Michelle Wu

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