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Faculty Detail     Name HARALD W SONTHEIMER   Campus Address CIRC 410B Zip 0021 Phone 205-975-5805 E-mail Sontheimer@uab.edu Other websites

Faculty Appointment(s) Appointment Type Department Division Rank Primary  Neurobiology  Neurobiology Professor Secondary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor Secondary  Neurology   Neurology Chair Office Professor Secondary  Pediatrics   Pediatrics Chair Office Professor Center  Civitan International Research Center  Civitan International Research Center Professor Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Center  General Clinical Research Center  Comprehensive Neuroscience Center Professor Center  Ctr for Glial Bio in Med  Ctr for Glial Bio in Med Professor Center  Neurology   Ctr Neurodegeneration & Exp Ther (CNET) Professor

Graduate Biomedical Sciences Affiliations Cell, Molecular, & Developmental Biology  Cellular and Molecular Biology Program  Hughes Med-Grad Fellowship Program  Integrative Biomedical Sciences  Medical Scientist Training Program  Neuroscience  Neuroscience Graduate Program  Neurosciences  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 Title The Role of Neuroglia in Brain Function and Disease Description 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 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  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  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   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  Montana, V and Sontheimer, H. Bradykinin promotes the chemo-tactic invasion of primary brain tumors. J. Neuroscience, 30;31(13):4858-67(2011).   21451024  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   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  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  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  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  First Prev   1 2 of  2  Next Last

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

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