Executive Director, School of Neuroscience
- Ph.D. in Neuroscience, University of Heidelberg, Germany
- I.D. Wilson Chair and Professor
- Director, Glial Biology in Health, Research, and Cancer Center
- Professor of Neurobiology, College of Science and Professor, VTCRI
Dr. Sontheimer, I. D. Wilson Chair and Professor of Neuroscience, is the Executive Director of the future School of Neuroscience at Virginia Tech, and Director of the Glial Biology in Health, Disease and Cancer Center at the Virginia Tech Carilion Research Center (VTCRI).
He joined VT in 2015 to establish the nation’s first School of Neuroscience, which will serve as the primary home for Neuroscience research and education at VT that includes training of Minors, Majors, Masters and Doctoral students. The School of Neuroscience will bridge many colleges drawing faculty from across multiple disciplines to offer an innovative, interdisciplinary Neuroscience curriculum.
A native of Germany, Dr. Sontheimer obtained a Masters degree in evolutionary comparative Neuroscience (1986), where he worked on the development of occulomotor reflexes. In 1989, he obtained a doctorate in Biophysics and Cellular & Molecular Neuroscience from the University of Heidelberg studying biophysical changes that accompany the development of oligodendrocytes, the principle myelinating cells of the nervous system. He moved to the United States, where he later became a citizen, for post-doctoral studies at Yale University. His independent research career began at Yale in 1991 on the role of glia in acquired epilepsy and continued at the University of Alabama Birmingham from 1994-2015 with a broad focus on the role of glial support cells in health and disease. His laboratory has made major discoveries that led to two clinical trials using novel compounds to treat malignant gliomas. His laboratory recently discovered that aberrant glutamate release from brain tumors is responsible for tumor associated epilepsy and a clinical trial is underway to address this condition.
In 2005 Dr. Sontheimer founded TransMolecular Inc., a biotechnology startup company devoted to the development of novel treatments for brain cancer. Following successful phase I and II clinical trials, the company was acquired by Morphotec Pharmaceuticals in 2011.
Dr. Sontheimer founded the Center for Glial Biology in Medicine at the University of Alabama Birmingham in 2006, the first center in the world to focus on the study of glial cells in health and diseases. He now directs a similar center with an even broader scope at the VTCRI.
From 2005 to 2015, Dr. Sontheimer directed the Civitan International Research Center, a philanthropically supported center devoted to the study and treatment of children with developmental disabilities, ranging from Down's syndrome to Autism. In this capacity, Dr. Sontheimer was tasked with explaining complex scientific processes to a lay audience.
Recognizing the need to further educate the public about neurological disorders using language that is accessible to an educated public, Dr. Sontheimer recently wrote a textbook entitled “Diseases of the Nervous system”, (store.elsevier.com/9780128002445) a book also used as text accompanying the Clinical Neuroscience course he teaches at VT.
Dr. Sontheimer is a dedicated and enthusiastic educator who has trained many undergraduates and over 50 graduate students and post-doctoral fellows. He has published over 160 peer-reviewed publications. He is a sought-after speaker and regularly participates in national and international conferences. He serves on numerous advisory boards for many national and international agencies including the German Max Plank Society, the MIT Press, National Institute of Health, Citizens United for Epilepsy and American Brain Tumor Association.
Sontheimer laboratory: Role of Glial in Neurological Illnesses and Cancer
Glial cells support normal brain function by maintaining ion and neurotransmitter homeostasis, by regulating local blood flow and by stabilizing the blood brain barrier. Many diseases present with an impairment of one or multiple of these functions.
The laboratory uses multi-photon laser scanning microscopy to study glial-vascular interactions and changes thereof in diseases ranging from Alzheimer and Epilepsy to Cancer. We use electrophysiology to study cell excitability and EEG recording to study seizures. Specific projects include the following:
- Changes in glial function in Alzheimer Disease: We are studying the hypothesis that the gradual buildup of amyloid is toxic to astrocyte process causing the retraction of their endfeet from blood vessels. This in turn causes a failure of tight junction proteins to form and the blood brain barrier breaks down causing entry of harmful blood born molecules into the brain. Loss of astrocytic endfeet also impairs activity dependent regulation of local blood flow and, the resulting hypoperfusion may underly cognitive loss in Alzheimer.
- Glia as drivers of abnormal neural activity in Epilepsy: Lesional epilepsy resulting from trauma, infection, tumors or stroke present with a reactive glial response called reactive gliosis. This is characterized by the release of extracellular matrix degrading proteases which alter the perineuronal matrix that stabilizes the function of GABAergic interneurons. These change their electrical properties to become hyperexcitable. Reactive astrocytes also loose their ability to clear neuronally released glutamate from the brain. Together tehse defects cause abnormal hyperexcitability that gives rise to seizures.
- Neurodegenerative properties of malignant glial derived brain tumors: Gliomas are tumors derived from astrocytes or glia precursor cells. They form rapidly expanding masses that send of individuals cells to infiltrate the surrounding brain and develop satellite tumors. This diffuse infiltration makes complete surgical resection essentially impossible. Cells invade along blood vessels dislodging astrocyte endfeet from the blood vessels resulting in loss of blood brain barrier function permitting entry of blood born molecules and peripheral immune cells. The tumor-infiltrated brain becomes progressively compromised, with pronounced neuronal cell death and edema being common. This is in large parts due to assiduous release of glutamate from the tumor via a highly expressed cysteine-glutamate antiporter. This amino-acid transporter serves to supply cystine for the production of the cellular reducing agent glutathione. Hence peritumoral glutamate toxicity is a collateral damage of the tumors intrinsic synthetic activity. The underlying transporter is regulated by p53 and CD44 providing novel targets to inhibit the glutamate release underlying the neurodegenerative biology of these tumors. A pharmacological blocker was used successfully by the Sontheimer lab in a recent clinical study.
- Robert SM, Buckingham SC, Campbell SL, Robel S, Holt KT, Ogunrinu-Babarinde T, Warren PP, White DM, Reid MA, Eschbacher JM, Berens ME, Lahti AC, Nabors LB, Sontheimer H. (2015). SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Science Translational Medicine 7(289).
- Robel S, Buckingham SC, Boni JL, Campbell SL, Danbolt NC, Riedmann T, Sutor B, Sontheimer H. (2015). Reactive astrogliosis causes the development of spontaneous seizures. Journal of Neuroscience 35(8), 3330-45.
- Sontheimer HW. (2015). Diseases of the Nervous System. Elsevier.
- Campbell SL, Robel S, Cuddapah VA, Robert S, Buckingham SC, Kahle KT, Sontheimer H. (2015). GABAergic disinhibition and impaired KCC2 cotransporter activity underlie tumor-associated epilepsy. Glia 63(1), 23-36.
- Seifert S, Sontheimer H. (2014). Bradykinin enhanced the invasion of malignant glioma into the brain parenchyma by inducing cells to undergo amoeboid migration. Journal of Physiology 592(22).
- Cuddapah VA, Robel S, Watkins S, Sontheimer H. (2014). A neurocentric perspective on glioma invasion. Nature Reviews in Neuroscience 15(7), 455-65.
- Robert SM, Sontheimer H. (2014). Glutamate transporters in the biology of malignant gliomas. Cellular and Molecular Life Sciences 71(10).
- Turner KL, Honasoge A, Robert SM, McFerrin MM, Sontheimer H. (2014). A proinvasive role for the Ca(2+)-activated K(+) channel KCa3.1 in malignant glioma. Glia.
- Watkins S, Robel S, Kimbrough IK, Robert SM, Ellis-Davies G, Sontheimer H. (2014). Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells. Nature Communications 5.
Books and Book Chapters:
- Kettenmann, H., Backus, K.H., Berger, T.B., Sontheimer, H., and Schachner, M.: Neurotransmitter receptors linked to ionic channels in cultured astrocytes: An electrophysiological approach. Differentiation and Functions of Glial cells, 203-211, Alan R. Liss. (1990).
- Ransom, B.R., Kettenmann, H., and Sontheimer, H.: Characteristics of electrical coupling between mammalian glial cells studied in vitro. Functions of Neuroglia, Vol.2, A. Roitbak (ed.), (1992).
- Sontheimer, H.: The use of laser photo-bleaching to study gap-junctions. Electophysiological Methods for In Vitro Studies in Vertebrate Neurobiology, H. Kettenmann, R. Grantyn (eds.), Wiley-Liss, New York, 343-348 (1992).
- Ransom, B.R. and Sontheimer, H.: Cell-cell coupling demonstrated by intracellular injection of the fluorescent dye Lucifer Yellow. In: Electophysiological Methods for In Vitro Studies in Vertebrate Neurobiology, H. Kettenmann, R. Grantyn (eds.), Wiley-Liss, New York, 336-342 (1992).
- Black, J.A., Sontheimer, H., Minturn J.E., Ransom, B.R., and Waxman, S.G.: The expression of sodium channels in astrocytes in situ and in vitro. In: Progress in Brain Research, Yu, A.C.H., Sykova, E., Hertz, L., Norenberg, M., and Waxman, S.G. (eds.), Elsevier, Amsterdam, Vol. 94:89-107 (1992).
- Waxman, S.G., Sontheimer, H., Black, J.A., Minturn, J.E., and Ransom, B.R.: Dynamic aspects of sodium channel expression in astrocytes. Advances in Neurology, Seil, F.J. (ed.), Raven Press, New York, Vol. 59:135-155 (1993).
- Sontheimer, H. and Ritchie, J.M.: Voltage-gated Sodium and Calcium Channel Expression by Satellite Cells. NEUROGLIA, Ransom, B.R. and Kettenmann, H. (eds), Oxford, New York, p202-220 (1995).
- Black, J.A., Sontheimer, H., Oh, Y. and Waxman, S.G.: The oligodendrocyte, the perinodal astrocyte, and the central node of Ranvier. In: The Axon, Waxman, S.G., Kocsis, J.D., and Stys, P.K. (eds.), Oxford University Press, New York, p116-142 (1995).
- Waxman, S.G., Black, J.A., Sontheimer, H., and Kocsis, J. Glial cells and axo-glial interactions: Implications for demyelinating disorders. Clinical Neuroscience, 2: 202-210 (1994).
- Sontheimer, H. Whole cell patch-clamp recordings. In: Patch clamp techniques and protocols, Boulton, A.A., Baker, G.B., and Walz, W. (eds.), Humana Press, Totowa NJ, 37-87 (1995).
- Sontheimer, H. and Fernandez-Marques, E.. Ion channel expression and function in astrocytic scars. In: Molecular signalling and regulation in glial cells: A key to remyelination and functional repair, Jeserich, G., and Althaus, H.H. (eds.), Springer, Heidelberg, 101-113 (1996).
- Sontheimer, H. and Ye, Z. Glial glutamate transport as target for Nitric Oxide: consequences for neurotoxicity In: Progress in Brain Research, 118: 241-251 (1998).
- Sontheimer, H. Chloride and Potassium channels in glial cells. In: Membrane Physiology of glial cells, Progress in Brain Research, Elsevier Publishing (1998).
- Sontheimer, H. and Ransom, C.B. Whole cell patch-clamp recordings. In: Patch clamp techniques and protocols, Boulton, A.A., Baker, G.B., and Walz, W. (eds.), Humana Press, Totowa NJ, 35-67 (2002).
- Bordey, A., and Sontheimer H. Astrocytic changes associated with epileptic seizures: Neuroglia in the aging brain, J.S. deVellis (ed.)., Humana Press, Totowa NJ, (2003).
- Parkerson, K.A. and Sontheimer H. Specialized channels in astrocytes. In: Glial ó Neuronal Signaling, Hatten G.I. & Parpura V. (eds.) Kluver Academic Pub., 215-237 (2004).
- Olsen M.L., and Sontheimer, H. Ion channels in glial cells. NEUROGLIA, Ransom, B.R. and Kettenmann, H. (eds), Oxford, New York (2004).
- Sontheimer, H. Olsen, M.L. Whole cell patch-clamp recordings. In: Patch clamp techniques and protocols, Boulton, A.A., Baker, G.B., and Walz, W. (eds.), Neuromethods Vol 35: 35-67 (2006).
- M.L. Olsen and H. Sontheimer, Ionic Channels in Glia, Encyclopedia of Neuroscience, 3rd Edition, Larry Squire (ed.) Elsevier, pages 237-247 (2009).
- Sontheimer, H. Chlorotoxin (TM-601): A Cl– Channel Blocker Used To Treat Malignant Glioma. Goodman and Gilmans Pharmacology Update (2008).
- Ernest, N.-J. and H. Sontheimer, Glioma, Encyclopedia of Neuroscience, 3rd Edition, Ed. Larry R. Squire Elsevier, Pages 877-884 (2009).
- Sontheimer, H. Role of ion channels and amino-acid transporters in the biology of astrocytic tumors. In: Astrocytes in (patho)physiology of the nervous system (Parpura V, Haydon; PG, eds),: Springer, p 527-546, (2009)
- Lyons, S.A., and Sontheimer H. Peritumoral Epilepsy. Encyclopedia of Basic Epilepsy, Phil Schwartzkroin (ed.) Elsevier, 2009.
- Sontheimer. H. Chloride transport in glioma growth and invasion. In: Physiology and Pathology of Chloride Transporters and Channels in the Nervous System, Alvarez, Elsevier, page2 515-525. (2009).
- Weaver, A.K., and Sontheimer, H. The role of ion channels in the Etiology and Development of Gliomas. In: Structure, Function and Modulation of neuronal voltage-gated ion channels. V.K. Gribkoff and L.K. Kaczmarek (eds.) Wiley, p. 105-126 (2009)
- Cuddapah VA and Sontheimer, H. Novel therapeutic approaches to malignant gliomas. Pathological potential of Neuroglia: Possible new targets for medical intervention. Edited by V. Parpura and A. Verkhratsy, Springer (in press).
- Sontheimer HW. (2015). Diseases of the Nervous System. Elsevier.
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