Aaron J. Johnson, Ph.D., is interested in neuroimmunology, with a major emphasis on the role of CD8 T cells and the pore-forming molecule perforin on blood-brain barrier (BBB) disruption.
Despite the enormous burden of morbidity and mortality due to neurological diseases associated with central nervous system vascular permeability, the underlying molecular mechanisms of how inflammatory cells promote BBB disruption remain poorly understood. To understand the mechanism of immune-mediated BBB disruption, Dr. Johnson uses both virus and cerebral malaria mouse models. He has also incorporated mouse models of glioblastoma multiforme and brain atrophy into his research program.
- Blood-brain barrier (BBB) disruption. BBB disruption is a common feature of many devastating neurological diseases. An appreciation of how inflammation promotes BBB disruption is only starting to be realized. Dr. Johnson has determined that CD8 T cells have the capacity to rapidly alter the BBB, the mechanism of which is currently being defined.
- Immune contribution of brain atrophy. Brain atrophy, otherwise classified as neurodegeneration, is a common feature of neurological diseases as diverse as Alzheimer's disease, cerebral palsy, dementia, Pick's disease, Huntington's disease, Krabbe disease, multiple sclerosis (MS), epilepsy, encephalitis, neurosyphilis and neuroAIDS. Dr. Johnson is investigating the role of neuroinflammation in brain atrophy.
- Immunotherapy for brain cancer. Glioblastoma multiforme is a devastating brain cancer that is incurable by surgery, radiation or chemotherapy. Using model systems, Dr. Johnson and colleagues are working to boost immunity against brain tumors using novel virus-based vaccines.
Significance to patient care
Disruption of the blood-brain barrier is a common pathologic feature of numerous neurological diseases as diverse as glioblastoma, multiple sclerosis, acute hemorrhagic leukoencephalitis, epilepsy, HIV dementia, stroke, cerebral malaria and viral hemorrhagic fevers.
A better understanding of the mechanisms of blood-brain barrier disruption will improve treatment and outcomes for many patients with these diseases. In addition, defining inflammatory factors that contribute to opening of the blood-brain barrier also has application in the delivery of chemotherapeutic agents to the central nervous system. Finally, defining the role of inflammation in brain atrophy and vaccines for brain cancers will provide new modes of therapy for these devastating neurological diseases.
- Permanent member, Brain Injury and Neurovascular Pathologies Study Section, National Institute of Neurological Disorders and Stroke (NINDS), 2015-present
- Member, special emphasis panel, Clinical Neuroimmunology and Brain Tumors Study Section, National Institutes of Health (NIH), 2012-present
- Ad hoc reviewer, Gene and Drug Delivery Systems Study Section, NIH, 2014-2015
- Member, special emphasis panel, NeuroAIDS and other End-Organ Diseases Study Section, NIH, 2013
- NIH reviewer, American Recovery and Reinvestment Act of 2009, 2010