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Faculty Detail    
Campus Address CIRC 410B Zip 0021
Phone  (205) 975-5805
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Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Neurobiology  Neurobiology Professor Adjunct

Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Integrative Biomedical Sciences 
Medical Scientist Training Program 
Neuroscience Graduate Program 
Pathobiology and Molecular Medicine 
Waiting to be Seated 

Biographical Sketch 
Harald Sontheimer received his Ph.D. in cell biology and biophysics from the University of Heidelberg in 1989. 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 currently Professor of Neurobiology with secondary appointments in Cell Biology, Physiology and Neurology. In addition, Dr. Sontheimer serves as the Director for the Cellular & Molecular Biology Graduate Program. In 2005, Dr. Sontheimer was appointed Director of the "Civitan International Research Center", a center with clinical and basic research devoted to the study of developmental disabilities and mental retardation. In 2006, Dr. Sontheimer became Director of the "Center for Glial Biology In Medicine", the first research entity exclusively dedicated to the study of glial cells and their role in health and disease.

Research/Clinical Interest
The Role of Neuroglia in Brain Function and 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 currently studying mechanisms that allow glial cell migration during development, after injury and in malignancy. We are particularly 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 and a pharmacological Cl- channel inhibitor is currently being evaluated clinically. We also discovered that teh Neurotransmitter glutamate serves an important grwoth promoting role in these tumors. It is being released to elicit neuronal death in peritumoral tissue presumably to vacate space for the tumors expansion. Glutamate is released via a cystine-glutamate exchnager and it inhibition is showing promising effects in preclinical studies. 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.

Selected Publications 
Publication PUBMEDID
Ogunrinu, T., and Sontheimer, H. The L-Cystine/L-Glutamate exchanger, system xc- supports glioma growth under hypoxic conditions, J. Biological Chemistry, 285:37716-24 (2010).   20858898  
McCoy, E., Haas, B.R. and Sontheimer, H. Water Permeability Through Aquaporin-4 is Regulated by Protein Kinase C and Becomes Rate-Limiting for Glioma Invasion. Neuroscience: 168(4):971-81 (2010).   19761816 
Cuddapah, V. and Sontheimer, H. Molecular interaction and functional regulation of ClC-3 by Ca2+/calmodulin-dependent protein kinase II (CaMKII) in human malignant glioma. J. Biol. Chemistry, 285: 11188-11196 (2010).   20139089 
Olsen, M.L., Campbell, S, McFerrin, M., Floyd, C. and Sontheimer H. spinal cord injury causes a wide-spread, persistent loss of Kir4.1 and GLT-1 in vivo: potential benefits of treatment with 17-estradiol. Brain. 133: 1013-1025 (2010).   20375134 
Bomben, V. and Sontheimer, H. Disruption of Transient Receptor Potential Canonical 1 Channel causes incomplete cytokinesis and slows the growth of human malignant gliomas. GLIA: 58(10):1145-56 (2010).   20544850 
Montana, V and Sontheimer, H. Bradykinin promotes the chemo-tactic invasion of primary brain tumors. J. Neuroscience, 30;31(13):4858-67(2011).   21451024 
Bomben, V.C., Turner, K., Barclay, T.T., and Sontheimer H. Transient receptor potential canonical channels are essential for chemotactic migration of human malignant gliomas. J. Cellular Physiology, (2011) 226(7):1879-88.   21506118 
Cuddapah VA, and Sontheimer H. Ion Channels and the Control of Cancer Cell Migration. Am J Physiol Cell Physiol. Sep;301(3):C541-549 (2011)  21543740  
Haas, BR, Cuddapah, VA, Watkins, S., Rohn, K.J., Dt, T.E. and Sontheimer, H. With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume. Am. J. Physiology, Aug. 3, (2011).   21813709 
Buckingham, S. C., Campbell, S.L., Haas, B.R. Montana, V. Robel, S., Ogunrinu T. and Sontheimer, H., Glutamate Release by Primary Brain Tumors Induces Epileptic Activity, Nature Medicine, Sep 11. doi: 10.1038/nm.2453. (2011).:   21909104 
Hass, B., and Sontheimer, H. Inhibition of the Sodium-Potassium-Chloride Cotransporter Isoform-1 Reduces Glioma Invasion. Cancer Research, 70(13):5597-606. (2010).   2896443 
De Groot, J. and Sontheimer, H. Glutamate and the Biology of Gliomas. Glia, (2011) 59(8):1181-9.   3107875  

Cell migration, brain development, primary brain tumors, glioma, astrocytes, oligodendrocytes, stem cells, regeneration