The primary focus of research in this laboratory is the design and execution of experiments aimed at defining the molecular determinants and the physiological roles of the multiple, functionally diverse, types of voltage-gated ion channels expressed in the cardiovascular and nervous systems that underlie action potential generation, propagation and cell-cell communication. Additional studies are focused on defining the molecular mechanisms involved in the physiological regulation of the expression, properties and functioning of these channels and determining how these mechanisms go awry in inherited and acquired diseases of the cardiovascular and nervous systems.
Accumulating evidence suggests that native neuronal and cardiac voltage-gated ion channels function in macromolecular protein complexes, comprising pore-forming subunits and a variety of cytosolic and transmembrane accessory and regulatory proteins that influence channel expression and functioning. Although previous studies conducted in heterologous cells have shown that accessory/regulatory proteins influence channel stability, trafficking, localization and/or biophysical properties, the physiological roles of these proteins in the generation of native voltage-gated ion channels in cardiac and neuronal cells are poorly understood. To address these questions directly, we are using in vivo and in vitro molecular genetics strategies to manipulate channel subunit expression, together with electrophysiological, molecular, biochemical and immunohistochemical methods to assess the functional consequences of these manipulations directly and to define the underlying regulatory mechanisms.
Back Row: Wei Wang, Oladapo Alabede, Denye Mickens, Tracey Hermanstyne, Joey Ransdell
Front Row: Rick Wilson, Jeanne Nerbonne, Miguel Campos
1974 B.Sc., Chemistry, Framingham State College, Framingham, MA
1978 Ph.D., Organic Chemistry, Georgetown University, Washington, DC
2002- present Alumni Endowed Professor, Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, MO
1997 – 2001 Professor, Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, MO
1991 – 1996 Associate Professor, Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, MO
1985 – 1990 Assistant Professor, Department of Pharmacology, Washington University School of Medicine, St. Louis, MO
Honors and Awards
2002-present Alumni endowed Professor of Molecular Biology and Pharmacology
1984-1989 American Heart Association Established Investigator Award
1981-1983 American Heart Association Postdoctoral Fellowship Award
1979-1981 National Institutes of Health Postdoctoral Fellowship Award
1979 W. W. Zorbach Memorial Prize for the Outstanding Chemistry Ph.D. Dissertation, Georgetown University, Washington, D.C.
- Bosch, M.K., Carrasquillo, Y., Ransdell, J.L., Kanakmedala, A., Ornitz, D.M., and Nerbonne, J.M. Intracellular FGF14 (iFGF14) is required for spontaneous and evoked firing in cerebellar Purkinje neurons and for motor coordination and balance. Journal of Neuroscience 35: 6752-6769 (2015).
- Yang, K.C., Yamada, K.A., Patel, A.Y., Topkara, V.K., Ewald, G.A., Mann, D.L., and Nerbonne, J.M. Deep RNA sequencing reveals dynamic regulation of myocardial non-coding RNAs in the failing human heart and remodeling with mechanical circulatory support. Circulation 129:1009-1021(2014).
- Boczek, N.J., Ye, D., Wang, W., Johnson, E.K., Crotti, L., Teskr, D.J., Dagradi, F., Mizusawa, Y., Torchio, M., Alders, M., Guidicessi, J.R., Wilde, A.A., Schwarz, P.J., Nerbonne, J.M., and Ackerman, M.J. Characterization of SEMA3A-encoded semaphorine as a naturally occurring Kv4.3 protein inhibitor and its contribution to Brugada Syndrome. Circulation Research 115: 460-469 (2014).
- Foeger, N.C., Wang, W., Mellor, R.L., and Nerbonne, J.M. Stabilization of Kv4 protein by the accessory K+ channel interacting protein 2 (KChIP2) is required for the generation of native myocardial fast transient outward currents. Journal of Physiology 591: 4149-4166 (2013).
- Yang, K.-C., Ku, Y.-C., Lovett, M., and Nerbonne, J.M. Combined deep microRNA and mRNA sequencing identifies protective transcriptional signature of enhanced P13K signaling in cardiac hypertrophy. Journal of Molecular and Cellular Cardiology 53: 101-112 (2012).
- Carrasquillo, Y., Burkhalter, A., and Nerbonne, J.M. A-type K+ channels encoded by Kv4.2, Kv4.3 and Kv1.4 differentially regulate the intrinsic excitability of cortical pyramidal neurons. Journal of Physiology 590: 3877-3890 (2012).
- Granados-Fuentes, D., Norris, A.J., Carrasquillo, Y., Nerbonne, J.M., and Herzog, E.D. IA channels encoded by Kv1.4 and Kv4.2 regulate neuronal firing in the suprachiasmatic nucleus and circadian rhythms in locomotor activity. Journal of Neuroscience 32: 10045-10052 (2012).
- Marionneau, C., Carrasquillo, Y., Norris, A.J., Isom, L., Townsend, R.R., Link, A.J., and Nerbonne, J.M. The sodium channel accessory subunit, Nav1, regulates neuronal excitability through modulation of voltage-gated K+ channels. Journal of Neuroscience 32: 5716-5727 (2012).
- Norris, A.J., Foeger, N.C., and Nerbonne, J.M. Interdependent roles for accessory KChIP2, KChIP3 and KChIP4 in the generation of Kv4-encoded IA channels in cortical pyramidal neurons. Journal of Neuroscience 30: 13644-13655 (2010).
- Marionneau, C., Brunet, S., Flagg, T.P., Pilgram, T.K., Demolombe, S. and Nerbonne, J.M. Distinct cellular and molecular mechanisms underlie functional remodeling of repolarizing K+ currents with left ventricular hypertrophy. Circulation Research 102: 1406-1415 (2008).
- Nerbonne, J.M., and Kass, R.S. Molecular physiology of cardiac repolarization. Physiological Reviews 85: 1205-1253 (2005).