Date of Defense

4-17-2024

Date of Graduation

4-2025

Department

Biological Sciences

First Advisor

Christine Byrd-Jacobs

Second Advisor

Antonio Morales-Hernández

Third Advisor

Cindy Linn

Abstract

G protein-coupled receptor-associated sorting proteins (GPRASPs) represent a large family of proteins found in hematopoietic stem cells (HSCs). Two GPRASPs, GPRASP1 and GPRASP2, have been found to negatively regulate CXCR4, a master regulator of hematopoiesis whose dynamic regulation is required for appropriate trafficking of B-cells in the germinal center. GPRASP1 and GPRASP2 deficiency enhance HSC transplantation efficiency; however, this alteration increases the risk of developing B-cell lymphoma by stalling B-cell normal differentiation. Interestingly, a subgroup of diffuse large B-cell lymphoma (DLBCL) patients expresses low levels of GPRASP1 and GPRASP2 compared to healthy B-cells. Here, we tested the effects of GPRASP2 overexpression in human DLBCL cells to evaluate the impact of the gene in the disease’s malignancy and progression. We found GPRASP2 overexpression to increase cellular growth in parallel with improved survival and reduced cell-surface expression of CXCR4. Further, GPRASP2 overexpression did not impact quiescence within human DB cells. These results provide insight into the impact of GPRASP2 expression in B-cell lymphoma. Although further studies are necessary to better understand the molecular mechanisms affected by GPRASP2 in B-cell lymphoma, our results propose GPRASP2 as a potential therapeutic target.

Access Setting

Honors Thesis-Restricted

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