Assistant Professor
Internal Medicine
Pathology & Immunology
Email Contact Info
We are interested in the molecular mechanisms that regulate the recruitment of inflammatory cells into the central nervous system (CNS) and their affects on neuronal function. Common to both of these is the action of chemokines, which both recruit leukocytes into the CNS and signal through chemokine receptors present on neurons. These molecules have been observed to play various roles in the pathogenesis of many neuroinflammatory diseases such as Multiple sclerosis, Alzheimer’s disease and viral encephalitis.
Our experimental approach involves the development of in vitro and in vivo models of CNS mononuclear cell recruitment and neuronal chemokine receptor signaling responses. Using a cell culture model system composed of primary neuronal precursor cells, we have determined that activation of the neuronal chemokine receptor CXCR4 enhances signaling through classical neurotransmitter receptors such as the NMDA receptor. This interaction is particularly exciting given that NMDA receptors are known to be involved in the excitoxic neuronal injury that occurs during various inflammatory states. Studies using in vivo models for both autoimmune and viral encephalitides focus on identifying the chemokines and chemokine receptors responsible for the recruitment of mononuclear cells into the CNS during normal and inflammatory states and the mechanisms of chemokine up-regulation. These studies will advance our understanding of normal CNS immune surveillance and its relationship to the wide range in inflammatory patterns observed in various neuroinflammatory diseases. This information will also lead to the identification of novel therapeutic targets, which is much needed in an era where there is little to offer patients with these diseases.
Research Publications
Klein, R.S. and Rubin, J.B. Immune and nervous system CXCL12 and CXCR4: parallel roles in patterning and plasticity. Trends Immunol. 2004 Jun;25(6):306-14. (Invited Review)
Klein, R.S., Izikson, L., Means, T., Gibson, H.D., Lin, E., Sobel, R.A., Weiner, H.L., Luster, A.D. (2004) IP-10/CXCL10-independent induction of experimental autoimmune encephalomyelitis. J. Immunol. 172(1): 550-9.
Klein, R.S., Rubin, J.B.*, Gibson, E.D., DeHaan, E.N., Segal, R.A., Luster, A.D. (2001) SDF-1a induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells. Development, 128:1971-1981
Klein R.S., Williams K.C., Alvarez-Hernandez X., Westmoreland S., Force T., Lackner A.A., Luster A.D. (1999) Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: Implications for the neuropathogenesis of AIDS. J. Immunol. 163(3): 1636-46.
Contact Info
Robyn Klein, M.D., Ph.D.
Office Location: 7273 McDonnell Pediatric Research
Office Phone: 314-286-2140
Lab Phone: 286-2137
Campus Box: 8051
Fax: 362-9230
rklein@wustl.edu
