Tjalkens Laboratory
Laboratory Focus
The Tjalkens Laboratory investigates the role of neuroinflammation and glial cells (microglia and astrocytes) in neurodegenerative diseases, with a primary focus on Parkinson’s disease (PD), manganism, and related disorders. Our research examines how innate immune signaling in glia drives neuronal injury, protein aggregation (including α-synuclein), and mitochondrial dysfunction—key processes in basal ganglia disorders.
We integrate transgenic animal models, primary glial-neuronal cultures, high-content fluorescence imaging, and molecular approaches to identify mechanisms linking environmental neurotoxins (for example, heavy metals like manganese and pesticides like rotenone), viral infections, and chronic inflammation to neurodegeneration. A major goal is to develop targeted therapies that modulate glial inflammatory pathways to protect dopaminergic neurons and slow disease progression.
Active Research Projects
Our projects emphasize the interplay between environmental exposures, glial activation, and neuronal pathology.
Neuroinflammation in Parkinson’s Disease
Our team studies how inflammatory signaling in microglia and astrocytes produces neurotoxic factors that promote α-synuclein aggregation and dopaminergic neuron loss. We use transgenic models with cell-specific inhibition of pathways like NF-κB/IKK2 to define protective versus detrimental glial phenotypes.
Environmental Neurotoxins and Heavy Metal Neurotoxicity
Chronic or developmental exposure to manganese and other metals increases the risk for parkinsonism and cognitive impairment. We are investigating how these toxins trigger glial-mediated inflammation and mitochondrial dysfunction and using models to test interventions that mitigate injury.
Viral Models of Neurodegeneration
Infections with neurotropic viruses (H1N1 influenza, Western Equine Encephalitis Virus, SARS-CoV-2) can initiate or exacerbate inflammatory cascades leading to protein aggregation and long-term neurological deficits. Astrocyte signaling is a particular focus of our work.
Therapeutic Development
We are evaluating novel ligands for nuclear receptors (NR4A2/Nurr1) and glucocorticoid receptor modulators (PT150) to suppress harmful glial inflammation while preserving beneficial functions. These efforts are supported by awards such as the Department of Defense Neurotoxin Exposure Treatment Parkinson’s Investigator-Initiated Research Award.
Alzheimer’s Disease and Related Pathologies
Our team is exploring links between mitochondrial toxins, microglial activation, and aggregation of Aβ and Tau, with emphasis on astrocyte reactivity and cognitive outcomes.
Techniques central to our laboratory include multi-dimensional fluorescence imaging, transgenic and viral vector approaches, behavioral assessments (for example, gait analysis), and molecular profiling of inflammatory pathways.
Principal Investigator
Postdoctoral Fellows
Brenna Baird, PhD
Postdoctoral Fellow