Jeanne M. Nerbonne, Ph.D.
Alumni Endowed Professor of Molecular Biology and Pharmacology
Molecular Cell Biology Program
9900 Clinical Sciences Research Building
cardiovascular physiology, cell physiology, electrical remodeling, ion channels, neurophysiology
Molecular determinants of ion channel expression, distribution and functioning
Research in this laboratory explores the molecular, cellular and systemic mechanisms involved in the dynamic regulation of neuronal and cardiac membrane excitability. Investigators in this laboratory exploit a combination of biochemical, electrophysiological, immunohistochemical and molecular genetic techniques in studies focused on characterizing the voltage-gated ion channels expressed in different cell types, identifying the molecular correlates of these channels and delineating the molecular mechanisms controlling the expression, distribution and functioning of these channels.
A major focus of ongoing work is on defining the physiological roles of the various Ca++-independent, voltage-gated K+ (Kv) channels that control the heights and durations of action potentials in the myocardium and on determining the roles of these channels in the generation of normal cardiac rhythms. Using a variety of molecular genetic strategies and proteomics, ongoing studies are aimed at defining the roles of Kv channel accessory subunits and regulatory proteins in controlling the expression and the properties of Kv channels in the normal heart. Additional studies are focused on exploring the molecular mechanisms underlying Kv channel remodeling in the hypertrophied and failing heart and in other myocardial diseases associated with cardiac rhythm disturbances.
The other major focus of the research in this laboratory is on delineating the molecular mechanisms that control the expression, localization and functioning of Kv channels and voltage-gated Na+ (Nav) channels in neurons. Kv currents are key determinants of neuronal excitability, functioning to control resting membrane potentials, action potential waveforms, repetitive firing and the responses to synaptic inputs. Ongoing studies are focused on exploring the molecular basis of functional neuronal Kv and Nav channel diversity and on probing the molecular mechanisms controlling the properties, the expression, the trafficking and the distributions of these channels.
Bosch, M.K., Carrasquillo, Y., Ransdell, J.L., Kanakmedala, A., Ornitz, D.M., & 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). [PMCID: PMC ]
Yang, K.C., Yamada, K.A., Patel, A.Y., Topkara, V.K., Ewald, G.A., Mann, D.L., & 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).[PMCID: PMC3967509]
Nerbonne, J.M. Mouse models of arrhythmogenic cardiovascular disease: challenges and opportunities. Current Opinion in Pharmacology 15: 107-114 (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., & 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).
Carrasquillo, Y., & Nerbonne, J.M. IA channels: diverse regulatory mechanisms. The Neuroscientist 20: 104-111 (2014).
Foeger, N.C., Wang, W., Mellor, R.L., & 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).[PMCID: PMC3779109]
Yang, K.C., Ku, Y.C., Lovett, M., & Nerbonne, J.M. (2012) Deep microRNA and mRNA sequencing identifies protective transcriptional signature of enhanced P13Kalpha signaling in cardiac hypertrophy, Journal of Molecular and Cellular Cardiology 53: 101-112. [PMCID: PMC3372631]
Marionneau, C., Carrasquillo, Y., Norris, A.J., Isom, L., Townsend, R.R., Link, A.J., & Nerbonne, J.M. (2012) The sodium channel accessory subunit, Navbeta1, regulates neuronal excitability through modulation of voltage-gated K+ channels. Journal of Neuroscience 32: 5716-5727. [PMCID: PMC3347704]
Foeger, N.C., Norris, A.J., Wren, L.M., &Nerbonne, J.M. (2012) Augmentation of Kv4.2-encoded currents by accessory dipetidyl peptidases 6 and 10 subunits reflects selective cell surface Kv4.2 protein stabilization. Journal of Biological Chemistry 287: 9640-9650.[PMCID: PMC3308783]
Nerbonne, J.M. (2012) Repolarizing cardiac potassium channels: Multiple sites and mechanisms for CaMKII-mediated regulation. Heart Rhythm 8: 938-941.
Last Updated: 8/26/2016 2:05:12 PM