Laura Campisi, PhD
Assistant Professor, WashU Pathology & Immunology
- Email: firstname.lastname@example.org
Understanding the role of T cells in ALS-4
Amyotrophic Lateral Sclerosis (ALS) is an incurable, heterogeneous neurodegenerative disorder that affects motor neurons in the brain and spinal cord, causing progressive loss of voluntary muscle control. Interestingly, several ALS-associated genes have been shown to affect immune functions, and a variety of aberrant inflammatory events have been reported in patients and mouse models, suggesting that specific immune features can also account for both ALS heterogeneity and pathology.
We recently made the original discovery that ALS-4, a juvenile and slowly progressive form of ALS caused by mutations in the gene SETX, has a strong immune component, as wild-type bone marrow transplantation in ALS mutants halts disease manifestation. Strikingly, an increasing frequency of clonally expanded, terminally differentiated effector memory (TEMRA) CD8 T cells in the peripheral blood and in the central nervous system (CNS) of ALS-4 mice and patients correlates with disease progression. Interestingly, ALS-4-associated CD8 T cells seem to play a role in resistance to glioma growth in mice.
Our findings point toward an involvement of T cells in ALS pathobiology. Whether these cells contribute to neurodegeneration and what mechanisms are involved in their activation is unknown.
Our lab combines expertise in the study of the immune system in mice and humans with cutting-edge technology to test the novel theory of an antigen-specific T cell response detrimental in the context of neurodegeneration, but protective against cancer.
Consistent with the goals of the Hope Center, our research is seeking fundamental mechanisms of human pathology that can be translated into a better management of patients, and novel therapeutic strategies.