Dissertation Defense: The role of adaptive immunity in Parkinson's pathology following traumatic brain injury
Dissertation Defense: The role of adaptive immunity in Parkinson's pathology following traumatic brain injury
Colin Kelly
Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Pickrell Lab, School of Neuroscience
December 2, 2025, at 10 a.m.
Life Sciences 1, Room 101
More About the Candidate and Project
Education
Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate
Virginia Tech, B.S., Neuroscience
Training
Graduate Research Assistant, Pickrell Lab, School of Neuroscience
Mentors
Alicia Pickrell, Ph.D., Associate Professor, Director of Graduate Studies, School of Neuroscience
Committee Members
- Sujith Vijayan, Ph.D., Associate Professor, School of Neuroscience
- Michelle Olsen, Ph.D., Professor, Director, School of Neuroscience
- Adrian Figg, Ph.D., Assistant Professor, Department of Chemistry
Publications
Kelly, C., Milner, J.P., Lester, B.A., Brindley, S., Hernandez, L., Murdaugh, L., Wei ,X., Olsen, M.L., Buczynski, M.W., & Pickrell, A.M. (2025). Brain injury contributes to dopaminergic neurodegeneration, lewy body pathology, and parkinsonism preclincally with outcomes altered by T cell modulation. Submitted Oct 2025.
Biswas, S.R., Tomsick, P.L., Kelly, C., Lester, B.A., Milner, J.P., Henry ,S., Soto, Y., Brindley, S., DeFoor, N., Morton, P.D., & Pickrell, A.M. (2025) Impaired complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in leigh syndrome mice. Submitted July 2025. In revisions.
Ladner, L. R., Tanchanco Ocampo, C., Kelly, C., Woodson, C. M., Marvin, E., Pickrell, A. M., Kehn-Hall, K., & Theus, M. H. (2025). The weight of multiple hits: how TBI and infectious encephalitis co-modulate adverse outcomes. Brain injury, 39(7), 588–597. https://doi.org/10.1080/02699052.2025.2450600
Fritsch, L. E.*, Kelly, C.*, Leonard, J., de Jager, C., Wei, X., Brindley, S., Harris, E. A., Kaloss, A. M., DeFoor, N., Paul, S., O'Malley, H., Ju, J., Olsen, M. L., Theus, M. H., & Pickrell, A. M. (2024). STING-Dependent Signaling in Microglia or Peripheral Immune Cells Orchestrates the Early Inflammatory Response and Influences Brain Injury Outcome. The Journal of neuroscience : the official journal of the Society for Neuroscience, 44(12), e0191232024. https://doi.org/10.1523/JNEUROSCI.0191-23.2024. * Indicates co-first authorship.
Gudenschwager-Basso, E. K., Shandra, O., Volanth, T., Patel, D. C., Kelly, C., Browning, J. L., Wei, X., Harris, E. A., Mahmutovic, D., Kaloss, A. M., Correa, F. G., Decker, J., Maharathi, B., Robel, S., Sontheimer, H., VandeVord, P. J., Olsen, M. L., & Theus, M. H. (2023). Atypical Neurogenesis, Astrogliosis, and Excessive Hilar Interneuron Loss Are Associated with the Development of Post-Traumatic Epilepsy. Cells, 12(9), 1248. https://doi.org/10.3390/cells12091248
Fritsch, L. E., Kelly, C., & Pickrell, A. M. (2023). The role of STING signaling in central nervous system infection and neuroinflammatory disease. WIREs mechanisms of disease, 15(3), e1597. https://doi.org/10.1002/wsbm.1597
Kowalski, E. A., Soliman, E., Kelly, C., Basso, E. K. G., Leonard, J., Pridham, K. J., Ju, J., Cash, A., Hazy, A., de Jager, C., Kaloss, A. M., Ding, H., Hernandez, R. D., Coleman, G., Wang, X., Olsen, M. L., Pickrell, A. M., & Theus, M. H. (2022). Monocyte proinflammatory phenotypic control by ephrin type A receptor 4 mediates neural tissue damage. JCI insight, 7(15), e156319. https://doi.org/10.1172/jci.insight.156319
About this Dissertation
Traumatic brain injury (TBI) increases the risk of Parkinson’s disease (PD) development later in life, but the molecular and cellular mechanisms are unknown driving this relationship. A single, mild brain injury can activate both resident and peripheral neuroinflammatory signaling pathways that are similarly activated in the brains of PD patients, likely increasing susceptibility to neurodegeneration. Previous studies have demonstrated that specific subtypes of T cells mediate inflammation in preclinical models of PD in response to the neurotoxic accumulation of alpha synuclein. Certain T cell populations are also known to be activated and recruited to the brain parenchyma at subacute timepoints post-brain injury, and can persist chronically, negatively impacting TBI outcome. Using models of both murine TBI and PD, we evaluated how a pre-existing neuroinflammatory event may exacerbate PD-associated pathologies and behavior. Our transcriptomic analysis of mRNA from purified dopaminergic neurons of mice 90 days post mild TBI (mTBI) revealed upregulation of genes related to neuroinflammation, peripheral immune signaling, and IFN-y, in addition to dysregulation of genes known to play a role in PD. Quantification of dopaminergic neurons in the substantia nigra showed significant cell death at 90 days post-injury compared to sham controls, with associated alterations in striatal neurotransmitter levels, like dopamine, leading to behavioral phenotypes. At that same time point, CD8+ T cells are present throughout the brain and around the substantia nigra. When mTBI is induced 30 days prior to induction of PD-associated pathologies via intrastriatal injections of alpha synuclein preformed-fibrils, a similar susceptibility of DA neurons is observed, in addition to an increased severity in alpha synuclein propagation. To examine the role of adaptive immunity in these outcomes, Rag2 KO mice were exposed to the same experimental conditions and displayed significant neuroprotection of the DA neuron population compared to wildtype animals. Taken together, these findings indicate the possibility of a sustained peripheral immune cell infiltration after injury and could support a complex, persistent, and detrimental crosstalk between both resident and peripheral immune cells which negatively affects DA neurons.