The SINTN seminar series proudly presents

Harald Sontheimer

New Treatments for Primary Brain Tumors: Ion Channels and Amino-acid Transporters as Drug Targets

Harald Sontheimer Ph.D.
Professor Neurobiology; Director Center for Glial Biology in Medicine; Director Civitan International Research Center
The University of Alabama Birmingham

Website: Sontheimer lab Web Site

Abstract:

Glial-derived tumors account for 50% of all primary brain malignancies
and are highly resistant to treatment. This stems in parts from their
ability to diffusely infiltrate normal brain thereby evading surgical
resection. This presentation will illustrate how invading glioma cells
utilize ion channels to dynamically adjust their cell shape and volume
enabling them to traverse the tortuous extracellular brain spaces.
Evidence will be presented that channel inhibitors can disrupt cell
invasion in vitro and in vivo with promising results obtained in a
recent phase II clinical trial. Glioma diagnosis is frequently preceded
by unexplained seizures. This lecture will develop the case that
peritumoral seizures are the result of glutamate being released by tumor
cells via an amino-acid transporter that's serves the cellular synthesis
of glutathione. Glutamate is released as an obligatory byproduct and
causes the aberrant excitation of peritumoral neurons, which leads to
seizures and ultimately excitotoxic injury. Data from an ongoing phase I
clinical study will illustrate the potential of targeting this pathway
in the treatment of newly diagnosed glioma patients.

Recent Papers:

[1]Habela, C.W, Olsen M,L., Sontheimer, H. ClC3 is a critical regulator of the cell cycle in normal and malignant glial cells. J. Neuroscience, 28:9205-17, (2008).

[2]120. Ernest, N.-J, Habela, C.W. and Sontheimer, H. Cytoplasmic condensation is both necessary and sufficient to induce apoptotic cell death. J. Cell Sci., 121:290-297 (2008)

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