Author ORCID Identifier

0000-0001-9940-1979

Date of Award

8-21-2026

Document Type

Thesis (Ph.D.)

Department or Program

Molecular and Systems Biology

First Advisor

Matthew C. Havrda

Second Advisor

Patricia Pioli

Abstract

Parkinson’s disease (PD) is a progressive age-related neurodegenerative disorder characterized by both motor and non-motor symptoms. The poorly understood prodromal period, decades-long progression, and disease-phenotype heterogeneity continue to impede the development of preventive and curative therapies. A growing appreciation of immune system changes during the progression of PD suggests that evaluating peripheral immune cells may help identify signatures relevant to disease etiology. We aimed to expand our understanding of the peripheral immune compartment in PD via two lines of investigation: (1) by employing single-cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells (PBMCs) from a cohort of 12 patients with PD and 12 healthy controls, equally distributed by sex, and (2) by characterizing the function of Brain Protein I3 (BRI3), a relatively novel gene with undetermined function that is well restricted to myeloid cells in PBMCs. Genomic analyses indicated that PD-related changes were associated with sex, including metabolic and inflammatory alterations; additional pathways and gene expression profiles associated with PD were identified in myeloid and T cell subsets. In THP-1 monocyte-like cell line models, BRI3 emerged as a candidate regulator of cell survival and stress response. This work provides new evidence of peripheral immune cell changes in PD utilizing high-resolution transcriptomics and in vitro functional assays.

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