Primary Department Affiliation: Neurobiology
Primary Research Area: Neurodegeneration and Neurodegenerative Disorders
CNS Cancer Biology and Treatment
Ion Channels and Synaptic Function
Neurodevelopment and Developmental Disabilities
The Role of Neuroglia in Brain Function & Disease
Glial cells constitute over 50% of brain cells, yet their involvement in normal brain function is not fully understood. Unlike neurons, glial cells can migrate and divide in the adult brain and might act as stem cells, allowing repair of the brain after injury and disease. Uncontrolled proliferation of glial cells causes gliomas, the most deadly form of cancer. These tumors show invasive migration into normal brain, which impedes successful therapy. The transition between stem cells, normal glia and gliomas is poorly understood, as are biological adaptations that allow these cells to migrate and navigate through compact tissues.
The broad goal of our laboratory is to understand how glial cells contribute to neuronal function in the healthy and diseased brain. We are studying mechanisms that allow glial cell migration during development, after injury and in malignancy. We are interested in intrinsic adaptation that facilitate cell shape changes during migration and in the signals by which cells communicate with the normal brain environment. We are seeking to determine whether malignant transformation or acute injury induces novel invasion mechanisms or whether cells invoke the same machinery used for cell migration during brain development. We recently discovered that the secretion of Cl- through ion channels is an essential component for the invasion of glioma cells which led to a Cl- channel inhibitor being evaluated clinically.
We are using a variety of techniques ranging from molecular biology, confocal and fluorescent cell imaging techniques to patch-clamp electrophysiology and a variety of cell migration/invasion models. We are routinely comparing properties of normal glial cells to glial cells associated with nervous system diseases. These studies employ primary cells and tissues derived from biopsies of patients presenting with glial tumors or other nervous system diseases.
Harald Sontheimer (b. 1960) received his Ph.D. in cell biology and biophysics from the University of Heidelberg in 1988. He received postdoctoral training at Yale University, School of Medicine where he was appointed as Assistant Professor of Neurology and Neurobiology from 1991-1994. He is now Professor of Neurobiology.