Linda J. Van Eldik
Title: Professor
Research area: Brain inflammation, molecular glial biology, and neurodegenerative disorders
Degree: Ph.D., Duke University, Durham, NC
Voice: 312.503.0697
Fax: 312.503.0007
e-mail: vaneldik@northwestern .edu

Detailed research description:
Our lab 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.

Representative publications:

Hu J, Akama KT, Krafft GA, Chromy BA and Van Eldik LJ
 (1998) Amyloid peptide activates cultured astrocytes:
  morphological alterations, cytokine induction and nitric
  oxide release. Brain Research 785:195-206.

LaDu MJ, Gilligan SM, Lukens JR, Cabana VG, Reardon
  CA, Van Eldik LJ and Holtzman DM (1998) Nascent
  astrocyte particles differ from lipoproteins in CSF. J
  Neurochem70:2070-2081.

Akama KT, Albanese C, Pestell RG and Van Eldik LJ
  (1998) Amyloid beta-peptide stimulates nitric oxide
  production in astrocytes through an NFkB-dependent
  mechanism. Proc Natl Acad Sci USA 95:5795-5800.

Birukov KG, Schavocky JP, Shirinsky VP, Chibalina MV,
  Van Eldik LJ and Watterson DM (1998) The
  organization of the genetic locus for chicken myosin light
  chain kinase is complex: multiple proteins are encoded
  and exhibit differential expression and localization. J
  Cellular Biochem 70:402 -413.

Hu J, LaDu MJ and Van Eldik LJ (1998) Apolipoprotein E
  attenuates amyloid induced astrocyte activation. J
  Neurochem 71:1626-1634.

Petrova TV, Akama KT and Van Eldik LJ (1999)
  Cyclopentenone prostaglandins suppress activation of
  microglia: downregulation of inducible nitric oxide
  synthase by 15-deoxy-?12,14 prostaglandin J2. Proc
  Natl Acad Sci USA 96:4668-4673.

Watterson DM, Schavocky JP, Guo L, Weiss C,
  Chlenski A, Shirinsky VP, Van Eldik LJ and Haiech J
  (1999) Analysis of the kinase-related protein gene found
  at human chromosome 3q21 in a multi-gene cluster:
  organization, expression, alternative splicing and
  polymorphic marker. J Cellular Biochem 75:481-491.

Mirzoeva S, Koppal T, Petrova TV, Lukas TJ, Watterson
  DM and Van Eldik LJ (1999) Screening in a cell based
  assay for inhibitors of microglial nitric oxide production
  reveals calmodulin regulated protein kinases as potential
  drug discovery targets. Brain Research 844:126-134.

Petrova TV, Akama KT and Van Eldik LJ (1999) Selective
  modulation of BV-2 microglial activation by prostaglandin
  E2: differential effects on endotoxin-stimulated cytokine
  induction. J Biol Chem 274:28823-28827.

Hu J and Van Eldik LJ (1999) Glial-derived proteins
  activate cultured astrocytes and enhance beta -amyloid-
  induced astrocyte activation. Brain Research 842:46-54.

Kudryashov DS, Chibalina MV, Birukov KG, Lukas TJ,
  Sellers JR, Van Eldik LJ, Watterson DM and
  Shirinsky VP (1999) Unique sequence of a high
  molecular weight myosin light chain kinase is involved in
  interaction with actin cytoskeleton. FEBS Lett, 463:67-71.

Petrova TV, Hu J and Van Eldik LJ (2000) Modulation of
  glial activation by astrocyte-derived S100B: differential
  responses of astrocyte and microglial cultures. Brain
  Research 853:74-80.

Lee ISM, Suzuki M, Hayashi N, Hu J, Van Eldik LJ,
  Titani K and Nishikimi M (2000) Copper dependent
  formation of disulfide-linked dimer of S100B protein,
  Arch Biochem Biophys 374:137-141.

Akama KT and Van Eldik LJ (2000) Beta-Amyloid
  stimulation of inducible nitric oxide synthase in
  astrocytes is interleukin-1beta-dependent and involves a
  TRAF6-dependent signaling mechanism. J Biol Chem
  275: 7918-7924.