Linda J. Van Eldik, PhD Professor Cell and Molecular Biology Brain Inflammation, Molecular Glial Biology, and Neurodegenerative Disorders Curricula: Cancer Biology       Cell Biology       Neurobiology Pharmacology and Toxicology       Structural Biology and Biochemistry E-mail:   vaneldik@northwestern.edu

Click here to visit the Van Eldik lab web site.

My laboratory focuses on brain inflammation — the activation of glial cells — a critical and detrimental feature of several neurodegenerative disorders, including Alzheimer’s disease, AIDS-related dementia, multiple sclerosis, and stroke-induced ischemia. Our overall aim is to identify and characterize logical drug discovery targets for the development of therapeutics to rectify this inflammatory process.

We employ multidisciplinary approaches rooted in molecular and cellular biology, as well as in protein-based chemistry, including: molecular manipulation of intracellular signal transduction pathways, promoter and gene expression analyses, high throughput screening methods for enzymes and inhibitors, protein structure-function analyses, and computerized structure-based inhibitor design.

By using these approaches, our lab has shown that glial activation is a robust, neuroinflammatory process that involves the complex coordination of signal transduction pathways, gene expression, and protein modulation. Moreover, a significant consequence of this glial activation is the generation of pro-inflammatory and oxidative stress responses. Inflammation and oxidative stress in the brain can be neurotoxic, and are suggested to be an important component in neuropathogenesis.

Current studies include investigation of how activated glia participate in transgenic models of disease and human pathology, the interactions of neurons and activated glia during inflammation, and discovery of ligand modulators of glial activation pathways. Another area of interest in the lab is on the cell and molecular biology of glial cell tumors (gliomas).

Publications:

Akama KT and Van Eldik LJ (2000) b-Amyloid stimulation of inducible nitric oxide synthase in astrocytes is interleukin-1b- and tumor necrosis factor-a (TNFa)-dependent, and involves a TNFa receptor-associated factor- and NFkB-inducing kinase-dependent signaling mechanism. J Biol Chem 275: 7918-7924.

LaDu MJ, Shah JA, Reardon K, Getz GS, Bu G, Hu J, Guo L and Van Eldik LJ (2000) Apolipoprotein E receptors mediate the effects of b-amyloid on primary astrocyte cultures. J Biol Chem 275:33974-33980.

Engelhard HH, Duncan HA, Kim S, Criswell PS and Van Eldik LJ (2001) Therapeutic effects of sodium butyrate on glioma cells in vitro and in the rat C6 glioma model. Neurosurgery 48:616-624.

Lam AGM, Koppal T, Akama KT, Guo L, Craft JM, Samy B, Schavocky JP, Watterson, D.M. and Van Eldik LJ (2001) Mechanism of glial activation by S100B: involvement of the transcription factor NFkB. Neurobiol Aging 22: 765-772.

Sheng JG, Jones RA, Zhou XQ, McGinness JM, Van Eldik LJ, Mrak RE and Griffin WST (2001) Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in Alzheimer’s disease: potential significance for tau protein phosphorylation. Neurochem Intl 39: 341-348.

Watterson DM, Mirzoeva S, Guo L, Whyte A, Bourguignon J-J, Hibert M, Haiech J and Van Eldik LJ (2001) Ligand modulation of glial activation: cell permeable, small molecule inhibitors of serine-threonine protein kinases can block induction of interleukin-1b and nitric oxide synthase II. Neurochem Intl 39: 459-468.

Peskind ER, Griffin WST, Akama KT, Raskind MA and Van Eldik LJ (2001) Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer’s disease. Neurochem Intl 39: 409-413.

Mirzoeva S, Sawkar A, Zasadzki M, Guo L, Velentza A, Dunlap V, Bourguignon J-J, Ramstrom H, Haiech J, Van Eldik LJ and Watterson DM (2002) Discovery of a 3-amino-6-phenylpyridazine derivative as a new synthetic anti-neuroinflammatory compound. J Med Chem 45: 563-566.

Watterson DM, Haiech J and Van Eldik LJ (2002) Discovery of new chemical classes of synthetic ligands that suppress neuroinflammatory responses. J Mol Neurosci 19:89-94.

Wainwright MS, Rossi J, Schavocky J, Crawford S, Steinhorn D, Velentza AV, Zasadzki M, Shirinsky V, Jia Y, Haiech J, Van Eldik LJ and Watterson DM (2003) A protein kinase involved in lung injury susceptibility: evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment. Proc Natl Acad Sci USA 100: 6233-6238.