RESEARCH INTERESTS
Viral infection of the central nervous system (CNS) results in neuroinflammation and are associated with the development of many neurological disorders. My research interest is to study how viral-host interactions are associated with the development of neuroinflammatory and neurodegenerative diseases, focusing mechanistically on the involvement of CNS-infiltrating immune cells to the development of epilepsy (program 1) and multiple sclerosis (program 2).
Our Goal: shed insight into disease mechanisms, allowing for the development of new therapies to improve the lives of patients that suffer from neuroinflammatory and neurodegenerative conditions.
Program 1: Epilepsy
Temporal lobe epilepsy (TLE) is the most prevalent form of acquired epilepsy. While the precise mechanisms that lead to the development of TLE remain unclear, inflammation-induced by viral infection of the CNS is an important contributor. My research program is focused on understanding the role of brain infiltrating immune cells, such as macrophages, and how they contribute to cellular and environmental CNS changes that alter the excitability of neurons and induce seizures. To that end, we infect C57BL/6J mice intra-cranially (ic) with Theiler’s Murine Encephalomyelitis virus (TMEV). These mice develop convulsive seizures between 3-8 days post infection (pi), followed by a latent period, where no seizures are observed, but after several weeks, spontaneous recurrent seizures (epilepsy) are observed. This is the only mouse model of viral-induced TLE and provides a unique opportunity to study how infection and inflammation lead to epilepsy.
Program 2: Multiple Sclerosis
Multiple Sclerosis (MS) is a chronic and progressive neuroinflammatory autoimmune disease characterized by demyelination of axons. Genetic and environmental factors, such as viral infections are known to contribute to MS development and progression. This research program will initially focus on understanding how viral-induced CD8 T cells result in axonal damage and demyelination using the mouse model of TMEV-induced demyelinating disease (TMEV-IDD). In this model, SJL/J mice infected intra-cranially with TMEV develop persistent CNS infection with progressive demyelination and axonal damage, resulting in flaccid paralysis of hindlimbs. TMEV-IDD recapitulates many of the features of the progressive form of MS.
RELATED LINKS
Education History
| Undergraduate |
Sao Paulo State University |
BSc |
|---|---|---|
| Doctoral Training |
University of Utah |
PhD, Microbiology and Immunology |
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University of Utah |
Postdoctoral Fellow |
Selected Publications
Journal Article
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DePaula-Silva AB. The Contribution of Microglia and Brain-Infiltrating Macrophages to the Pathogenesis of Neuroinflammatory and Neurodegenerative Diseases during TMEV Infection of the Central Nervous System. Viruses. 2024 Jan 13;16(1). doi: 10.3390/v16010119. Review. PubMed PMID: 38257819; PubMed Central PMCID: PMC10819099.
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Sanchez JMS, DePaula-Silva AB, Libbey JE, Fujinami RS. Role of diet in regulating the gut microbiota and multiple sclerosis. Clin Immunol. 2022 Feb;235:108379. doi: 10.1016/j.clim.2020.108379. Epub 2020 Mar 7. Review. PubMed PMID: 32156562; PubMed Central PMCID: PMC7483914.
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DePaula-Silva AB, Bell LA, Wallis GJ, Wilcox KS. Inflammation Unleashed in Viral-Induced Epileptogenesis. Epilepsy Curr. 2021 Nov-Dec;21(6):433-440. doi: 10.1177/15357597211040939. eCollection 2021 Nov-Dec. PubMed PMID: 34924851; PubMed Central PMCID: PMC8652320.