Author ORCID Identifier

https://orcid.org/0000-0001-6990-6861

Date of Award

2025

Document Type

Thesis (Ph.D.)

Department or Program

Integrative Neuroscience

First Advisor

Dr. Lucas Salas

Second Advisor

Dr. Francesca Gilli

Abstract

Neuroinflammation is a critical physiological phenomenon implicated in most neurological disorders, either as a cause or a consequence of pathology. Our understanding of neuroinflammation is limited by the inability to directly profile the cells of interest. Thus, developing biomarkers of neuroinflammation is clinically urgent as we know neuroinflammation correlates with patient outcomes and treatment success. The recent advances in “omics” technologies, particularly epigenomics and transcriptomics, provides the opportunity for high-dimensional profiling of biospecimens for potential biomarkers. Within this dissertation, I demonstrate that biomarkers obtained from “omics” platforms can detect neuroimmunological phenomena in clinical and preclinical settings. In chapter one, DNA methylation-based biomarkers are utilized to demonstrate that immunological perturbations in the blood that are associated with Parkinson’s disease can manifest prior to the onset of motor deficits. In chapter two, I show that DNA methylation biomarkers can be utilized to measure immune infiltration in glioma biopsy samples, that these estimates correlate with patient survival, and that this approach is scalable and amendable to current clinical practices in using DNA methylation to aid in the diagnosis of glioma. Lastly, in chapter three, I demonstrate an optimized tissue processing method that allows for accurate transcriptomic profiling of the spinal cord meninges in a preclinical model of neuroinflammation. Altogether, this work underscores the potential of epigenomic and transcriptomic profiling for studying neuroinflammation in clinically or pathologically relevant samples. In the future, I hope to expand upon this work in a two-pronged approach in which I can continue to prepare “omics” based neuroinflammation biomarkers for clinical implementation as well as use these tools to learn more about the basic immunophysiology and immunopathology underlying neurological diseases.

Original Citation

The content of chapter 1 has been adapted from work published in Nature Parkinson’s Disease: Pike SC, Havrda M, Gilli F, Zhang Z, Salas LA. Immunological shifts during early-stage Parkinson's disease identified with DNA methylation data on longitudinally collected blood samples. NPJ Parkinsons Dis. 2024;10(1):21. Epub 20240111. doi: 10.1038/s41531-023-00626-6. PubMed PMID: 38212355; PMCID: PMC10784484.

The content of chapter 2 has been adapted from work published in Acta Neuropathologica Communications: Pike SC, Wiencke JK, Zhang Z, Molinaro AM, Hansen HM, Koestler DC, Christensen BC, Kelsey KT, Salas LA. Glioma immune microenvironment composition calculator (GIMiCC): a method of estimating the proportions of eighteen cell types from DNA methylation microarray data. Acta Neuropathol Commun. 2024;12(1):170. Epub 20241028. doi: 10.1186/s40478-024-01874-0. PubMed PMID: 39468647; PMCID: PMC11514818.

Download

Available for download on Wednesday, May 13, 2026

Share

COinS