Laboratory Page

Alfred L. George, M.D.,
Grant W. Liddle Professor of Medicine; Professor of Pharmacology; Chief, Division of Genetic Medicine; Director, Vanderbilt Institute for Integrative Genomics; Associate Chair for Science Education, Department of Medicine; Director, Physician-Scientist Training Program, Department of Medicine

Dr. George's laboratory is engaged in a broad spectrum of research activities aimed at elucidating the molecular genetics of ion channels, especially voltage-gated sodium, potassium and chloride channels. Specific isoforms of these ion channels have been linked to hereditary disorders of membrane excitability causing muscle disorders (periodic paralysis, myotonia), cardiac arrhythmias (long QT syndrome, Brugada syndrome, Andersen syndrome), and brain disorders (epilepsy, migraine).

In 1999, Dr. George established the Division of Genetic Medicine and currently serves as Division Chief. In 2005, he became the founding Director of the Vanderbilt Institute for Integrative Genomics. Dr. George was elected to the American Society of Clinical Investigation in 1998 and to the Association of American Physicians in 2001. He was a recipient of the Lucille P. Markey Scholar Award in Biomedical Sciences, American Heart Association Established Investigator Award, Vanderbilt University Chancellor's Award for Research, Elliot V. Newman Prize for Basic Science, 2002 Teaching Award for the Vanderbilt Department of Pharmacology, and the Javits Neuroscience Investigator Award from the National Institute of Neurological Diseases and Stroke.

Selected Recent Publications:

Kahlig, K.M., Rhodes, T.H., Pusch, M., Freilinger, T., Pereira-Monteiro, J.M., Ferrari, M.D., van den Maaagdenberg, A.M.J.M, Dichgans, M., and George, A.L., Jr. (2008) Divergent sodium channel defects in familial hemiplegic migraine. Proc Natl Acad Sci USA, 105:9799-9804.

Rhodes, T.E., Abraham, R.A., Welch, R.C., Vanoye, C.G., Crotti, L., Arnestad, M., Insolia, R., Pedrazzini, M., Ferrandi, C., Vege, A., Rognum, T., Roden, D.M., Schwartz, P.J., and George, A.L., Jr. (2008) Cardiac potassium channel dysfunction in sudden infant death syndrome. J Mol CellCardiol, 44:571-581.

Nguyen, T.P., Wang, D.W., Rhodes, T.H. and George, A.L., Jr.. (2008) Divergent biophysical defects caused by mutant sodium channels in dilated cardiomyopathy with arrhythmia. Circ Res, 102:364-371.

Wang, D.W., Desai, R.R., Crotti, L., Arnestad, M., Insolia, R., Pedrazzini, M., Ferrandi, C., Vege, A., Rognum, T., Schwartz, P.J., and George, A.L., Jr. (2007) Cardiac sodium channel dysfunction in sudden infant death syndrome. Circulation, 115:368-376.

Wilson , M.H., Coates, C.J., and George, A.L., Jr. (2007) PiggyBac-transposon mediated gene transfer in human cells. Molecular Therapy, 15:139-145.

Kahlig, K.M., Misra, S.N., and George, A.L., Jr. (2006) Impaired inactivation gate stabilization predicts increased persistent current for an epilepsy-associated SCN1A mutation. J Neurosci, 26:10958-10966.

Vanoye, C.G., Lossin, C., Rhodes, T.H., and George, A.L., Jr. (2006) Single-channel properties of human Na V1.1 and mechanism of channel dysfunction in SCN1A-associated epilepsy. J Gen Physiol, 127:1-14.

George, A.L., Jr.(2005) Inherited disorders of voltage-gated sodium channels. J ClinInvest, 115:1990-1999.

Rhodes , T.H., Lossin, C., Vanoye, C.G., Wang, D.W., and George, A.L., Jr. (2004) Non-inactivating voltage-gated sodium channels in severe myoclonic epilepsy of infancy. Proc Natl Acad Sci USA, 101:11147-11152.

Lossin, C., Rhodes, T.H., Desai, R.R., Vanoye, C.G., Wang, D.W., Carniciu, S., Devinsky, O., and George, A.L., Jr. (2003) Epilepsy-associated dysfunction of the voltage-gated neuronal sodium channel, SCN1A. J Neuroscience, 23:11289-11295.

Benson, D.W., Wang, D.W., Dyment, M., Knilans, T.K., Fish, F.A. Strieper, M.J., Rhodes, T.R., and George, A.L., Jr. (2003) Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest, 112:1019-1028.

Rogers , C.R, Vanoye, C.G., Sullenger, B.A., and George, A.L., Jr. (2002) Functional repair of a mutant chloride channel using trans-splicing ribozymes. J Clin Invest, 110:1783-1789.

Lossin, C., Wang, D.W., Rhodes, T.H., Vanoye, C.G., and George, A.L., Jr. (2002) Molecular basis for an inherited epilepsy. Neuron, 34:877-884.

Wallace, R.H., Wang, D.W., Singh, R., Scheffer, I.E., Phillips, H.A., Saar, K., Reis, A., Sutherland, G.R., Berkovic, S.F., George, A.L., Jr. and Mulley, J.C. (1998) Febrile seizures and generalised epilepsy caused by a mutation in the sodium channel subunit SCN1B. Nature Genetics, 19:366-370.

Fahlke , Ch., Yu, H.T., Beck, C.L., Rhodes, T., and George, A.L., Jr. (1997) Pore forming segments in voltage-gated chloride channels. Nature, 390:529-532.

Bennett, P.B., Jr., Yazawa, K., Makita, N., and George, A.L., Jr. (1995) Molecular mechanism of an inherited cardiac arrhythmia. Nature, 367:683-685.