Date on Master's Thesis/Doctoral Dissertation

12-2018

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Interdisciplinary and Graduate Studies

Degree Program

Interdisciplinary Studies (Individualized Degree), PhD

Committee Chair

Frieboes, Hermann

Committee Co-Chair (if applicable)

Arteel, Gavin

Committee Member

Beverly, Levi

Committee Member

Merchant, Michael

Committee Member

Cave, Matthew

Author's Keywords

extracellular matrix; liver injury; macrophages; tumor modeling; alcoholic liver disease; innate immunity

Abstract

The overarching goals of the current work are to fill key gaps in the current understanding of alcohol consumption and the risk of metastasis to the liver. Considering the evidence this research group has compiled confirming that the hepatic matrisome responds dynamically to injury, an altered extracellular matrix (ECM) profile appears to be a key feature of pre-fibrotic inflammatory injury in the liver. This group has demonstrated that the hepatic ECM responds dynamically to alcohol exposure, in particular, sensitizing the liver to LPS-induced inflammatory damage. Although the study of alcohol in its role as a contributing factor to oncogenesis and metastatic progression has not been extensively investigated in basic science, it is clear from numerous clinical reports and meta-analyses that it would be a benefit to patients to understand the complexity of their comorbidities on a molecular level. It is well recognized that intramural research efforts are needed to understand the associated pathologies. Using signatures of liver ECM to predict cell surface integrin binding profile can establish personalized data that can be used clinically to determine therapeutic targets.

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