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Resistin-Like Molecule Alpha Lentivirus and Utilizing Community Engaged Research to Tackle COVID-19 Health Disparities

Abstract

Macrophage-derived proteins play critical roles throughout all stages of the immune response to a variety of pathogens. Depending on the immunological challenge and the subsequent cytokines produced in response, macrophages will become classically (IFNγ) or alternatively activated (IL-4), with an entire spectrum of macrophage phenotypes existing between these two classifications. Upon activation, macrophages will produce a diverse array of proteins and cytokines to guide the immune response depending on the stimulus. Resistin-like molecule alpha (RELMα) is an example of such a protein that is secreted by alternatively activated M2-macrophages. Our laboratory has previously identified a variety of roles for RELMα in vivo and in vitro. However, knowledge gaps remain with regards to potential cell-extrinsic versus cell-intrinsic differences of immune regulating proteins on cell behavior and function. These include whether there is a difference in how a cell behaves when it expresses the protein or whether it encounters it extracellularly, or whether the function differs dependent on the cell-type, given that RELM is expressed by immune and non-immune cells. To begin addressing these questions, new tools are needed that allow overexpression in cell lines and primary cells. In the first part of this thesis, I sought to generate a RELMα over-expressing lentivirus to be later utilized in the efficient transduction of both cell lines and primary cells.

Community-based research has the potential to improve the possibility of reducing certain health disparities. The COVID-19 pandemic brought health disparities to the forefront, many of which existed before and were exacerbated by it. It then becomes the responsibility of researchers to engage within a community-based framework to use these opportunities and address the factors driving these disparities. Research conducted at the UC Riverside School of Medicine on COVID-19 in Riverside County has identified such disparities in the population, where Hispanic individuals were more likely to be severely infected with COVID-19. When opportunity arises in which community-engaged research should be performed, we offer the methodology and framework that was used in planning for our community-engaged research symposium that fostered a rich environment of academic and community collaboration. In the second part of my thesis, I will go into the community-engaged research I performed that allowed for the successful execution of a community-focused COVID-19 symposium.

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