Lester I. Binder
Rank: Professor
Research area: The Role of the Cytoskeleton in Neurodegeneration
Degree: Ph.D., Yale University
Voice: 312.503.0823
Fax: 312.503.7912
e-mail: l-binder@northwestern .edu

Detailed research description:
We study the role of microtubule-associated proteins (MAPs) in the normal and diseased nervous system. Most of our work has focused on tau, a protein thought to stabilize axonal microtubules, but that is also present in other cellular and subcellular compartments in the central nervous system. The functions of this extra-microtubule tau is not known although its association with ribosomes in neurons and astrocytes and with the rRNA gene clusters in nuclei and on chromosomes of dividing cells suggests some role in protein synthesis. We have also documented tau's presence in oligodendrocytes, perhaps associated with membrane vesicles, suggesting yet another function for this fascinating molecule.

Interest in tau is great in the medical community because we and others have shown that it is the major protein species in the paired helical filaments (PHFs). These filaments comprise the fibrillar pathologies found in the brains of patients with Alzheimer's Disease. Furthermore, many forms of human Frontal Lobe Dementias, that are characterized by tau filamentous inclusions, are caused by autosomal dominant mutations in tau. Using cellular, molecular and immunological techniques, my lab studies the mechanism of tau filament formation in vitro and in vivo and seeks to determine the functional consequences of tau polymerization to the neurodegenerative cascade.

Representative publications:

Wilson, D.M., and L.I. Binder. 1997. Free fatty acids
  stimulate the polymerization of tau and amyloid Ab
  peptides: In vitro evidence for a common effector of
  pathogenesis in Alzheimer's disease. Amer. J. Pathol.
  150: 2181-2195.

King, M. E., Ahuja, V., Wilson, D., Binder, L.I., and Kuret,
  J. 1999. Tau filament formation via pathological
  chaperones: Implications for Alzheimer's disease
  progression. Biochemistry, 38: 14851-14859.

King, M.E., Gamblin, T.C., Kuret, J., and Binder, L.I.
  2000. Differential assembly of human tau isoforms into
  straight and paired-helical filaments, in vitro. J.
  Neurochem., 74: 1749-1757.

Gamblin, T.C., King, M.E., Dawson, H., Vitek, M.,
  Kuret, J., Berry, R.W., and Binder, L.I. In vitro
  polymerization of tau protein monitored by laser light
  scattering: Method and application to the study of
  FTDP-17 mutants. Biochemistry, 39: 6136-6144.

Abraha, A., Ghoshal, N., Gamblin, T.C., Cryns, V.,
  Berry, R.W., Kuret, J., and Binder, L.I. 2000. C-terminal
  inhibition of tau assembly in vitro and in Alzheimer's
  Disease. J. Cell Sci. 113: 3737-3745.

(click images to enlarge)