ORCID

https://orcid.org/0000-0002-9612-7764

Date of Award

2-25-2024

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is a poorly understood, putative extracellular matrix protein. Several human traits and diseases are associated with SVEP1, including coronary artery disease, hypertension, type 2 diabetes, glaucoma, dementia, longevity, and platelet reactivity. This dissertation establishes a causal link between SVEP1 and human disease using Mendelian randomization and mouse models. It also provides insights into the disease mechanisms of the protein, including a novel interaction between SVEP1 and the orphan receptor Platelet endothelial aggregation receptor 1. The relevance of this interaction to platelet biology and its potential role in cardiometabolic disease is discussed. The viability of inhibiting SVEP1 to treat or prevent disease is also evaluated.

Language

English (en)

Chair and Committee

Nathan O Stitziel

Committee Members

Carmen M Halabi, Robert P Mecham, Joel D Schilling, Amber N Stratman

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