All ETDs from UAB

Advisory Committee Chair

Bin Ren

Advisory Committee Members

Yabing Chen

Adam Beck

Bart Rose

James George

Document Type

Dissertation

Date of Award

1-1-2025

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Vascular endothelial cells (ECs) are increasingly recognized as a distinct class of innate immune cells, with CD36, an innate immunity receptor, playing a pivotal role in regulating immune function and its regulation, angiogenesis, cancer progression, brain related disorder as well as the exchange of nutrients and waste. To investigate this further, we developed EC-specific CD36 knockout mice using the translating ribosome affinity purification (TRAP) technique. By isolating ribosome-bound mRNA directly from vascular endothelial cells in vivo in these knockout and control mice, we conducted deep RNA sequencing and transcriptional profiling. Our findings revealed that CD36 deficiency in brain endothelia led to the downregulation of gene signatures associated with innate immune memory, alongside changes in the expression of genes related to innate immunity and immune responses, which were linked to fatty acid (FA) metabolism. Additionally, single-nuclear RNA-seq analysis of brain tissues from Alzheimer’s disease (AD) patients highlighted the critical involvement of a subset of CD36-positive brain ECs in disease progression. . Endothelial cells in blood vessels and lymph nodes play a crucial role in regulating the spread of breast cancer. They contribute to tumor growth and metastasis by secreting various factors that activate breast cancer cells, including cytokines and breast cancer stem cell-related signals. To further elucidate the significance of endothelial cells in breast cancer progression, we examined the viability, migration, proliferation, and apoptotic potential of ER+ breast cancer cells. Our findings demonstrate that the combination of Fc3TSR and Everolimus effectively inhibits the growth of ER-positive breast cancer cells.

Comments

etdadmin_upload_1138018

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.