Research in the Nerbonne laboratory is focused on delineating the molecular, cellular and systemic mechanisms involved in the dynamic regulation of cardiac and neuronal membrane excitability in health and disease. Combining biochemical, electrophysiological, immunohistochemical and molecular genetic approaches, the focus of our work is on: (1) characterizing the biophysical properties and the functional roles of the voltage-gated potassium (Kv) and sodium (Nav) ion channels expressed in different myocardial and neuronal cell types; (2) defining the functional roles of these channels in shaping the waveforms of individual action potentials and controlling repetitive and rhythmic firing; (3) identifying the molecular correlates of native neuronal and myocardial Kv and Nav channels; (4) defining the physiological mechanisms controlling the expression, distribution and functioning of these channels; and (5) deciphering the mechanisms underlying the pathophysiological remodeling of native Kv and Nav channels in inherited and acquired cardiovascular and neurological diseases.
B.Sc., Chemistry, Framingham State College, Framingham, MA (1974)
Ph.D., Physical Organic Chemistry, Georgetown University, Washington, DC (1978)
Postdoctoral Research Fellow, Division of Biology, California Institute of Technology, Pasadena, CA (1982)
Senior Research Fellow, Division of Biology, California Institute of Technology, Pasadena, CA (1984)
2013-present Alumni Endowed Professor of Molecular Biology and Pharmacology, Departments of Developmental Biology and Medicine (dual appointment), Washington University School of Medicine
2013-2023 Director, Center for Cardiovascular Research, Department of Medicine, Cardiovascular Division, Washington University School of Medicine
2010-present Co-Director, Center for the Investigation of Membrane Excitability Diseases (CIMED), Washington University School of Medicine
2009-2013 Alumni Endowed Professor of Molecular Biology and Pharmacology, Department of Developmental Biology, Washington University School of Medicine
2006-present Professor, Department of Biomedical Engineering, School of Engineering, Washington University (secondary appointment)
2002-2008 Alumni Endowed Professor of Molecular Biology and Pharmacology, Department of Molecular Biology and Pharmacology, Washington University School of Medicine
1997-2001 Professor, Department of Molecular Biology and Pharmacology, Washington University School of Medicine
1991-1996 Associate Professor, Department of Molecular Biology & Pharmacology, Washington University School of Medicine
1985-1990 Assistant Professor, Department of Pharmacology, Washington University School of Medicine
Honors and Awards
2022-2023 President, Society of General Physiologists
2022 Fellow, International Society for Heart Research
2020-2021 President-elect, Society of General Physiologists
2018 Julius B. Kahn Distinguished Visiting Professor, Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL
2017 Third Annual Matthew N. Levy Distinguished Lecture, Department of Physiology and Biophysics, Case Reserve University School of Medicine, Cleveland OH
2017 Keynote Speaker, FASEB Ion Channel Conference, Steamboat Springs, CO
2016 Abboud Cardiovascular Center Distinguished Lecturer, University of Iowa Carver College of Medicine, Iowa City, IA
2016 Gold Heart Member, Basic Cardiovascular Sciences, American Heart Association
2015 Shining Star Award, Academic Women’s Network, Washington University School of Medicine
2013 Keynote Speaker, Dutch Heart Foundation Lecturer, Dutch Physiological Society 29th Annual Symposium, Adaptive Physiology, Utrecht, Netherlands
2013 Getz Distinguished Lecturer, Department of Biology, Branders University, Waltham, MA
2013 Visiting Distinguished Wiersma Professor of Neuroscience, Division of Biology, California Institute of Technology, Pasadena, CA
2012 Fellow, American Association for the Advancement of Science
2008 Distinguished Investigator Award, Washington University School of Medicine
2006 Davis Heart and Lung Research Institute Discovery Series Distinguished Lecturer, Ohio State University, Columbus, OH
2006-2007 Chair, Electrical Signaling, Transport and Arrhythmia Study Section, Center for Scientific Review, National Institutes of Health
2006 Silver Heart Member, Basic Cardiovascular Sciences, American Heart Association
2005 Nora Eccles Harrison Distinguished Lecturer, Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT
2004 Neurosciences Interdisciplinary Graduate Program Invited Speaker, Program in Neuroscience, Georgetown University, Washington, DC
2003 The Rudy Clarenburg Distinguished Lecturer, Kansas State University, Manhattan, KS
2003 Neurosciences Graduate Student Organization Invited Speaker, Division of Neuroscience, Baylor College of Medicine, Houston, TX
2002 Medical Science Graduate Student Association 10th Annual Symposium, Science Today! Keynote Speaker, University of Calgary, Banff, Canada
2002 Alumni Endowed Professor of Molecular Biology and Pharmacology
2001 Founding Fellow of the American Heart Association, Basic Cardiovascular Sciences
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.
- Yang, N.-D., Mellor, R.L., Hermanstyne, T.O., and Nerbonne, J.M. Effects of NALCN-encoded Na+ leak currents on the repetitive firing properties of SCN neurons depend on K+-driven rhythmic changes in input resistance. Journal of Neuroscience 2023: 43: 5132-5141.
- Angsutararux, P., Dutta, A., Marras, M., Abella, C., Mellor, R.L., Shi, J., Nerbonne, J.M.*, and Silva, J.R.* Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors. Journal of General Physiology 2023: 155: e202213300. *co-corresponding authors
- Ransdell, J.R., Moreno, J.D., Bhagavan, D., Silva, J.R., and Nerbonne, J.M. Intrinsic mechanisms in the gating of resurgent Na+ currents. eLife 2022: e70173.
- Zhu, W., Wang, W., Angsutararux, P., Mellor, R.L., Isom, L.L., Nerbonne, J.M.*, and Silva, J.R.* Modulation of the effects of Class-Ib antiarrhythmics on cardiac Nav1.5-encoded channels by accessory Navβ subunits. Journal of Clinical Investigation Insight 2021: 6: e143092. *co-corresponding authors
- Johnson E.K., Springer S.J., Wang W., Dranoff E.J., Zhang Y., Kanter E.M., Yamada K.A., Nerbonne J.M. Differential expression and remodeling of transient outward potassium currents in human left ventricles. Circulation: Arrhythmia and Electrophysiology 2018: 11: e005914.
- Ransdell, J.L., Dranoff, E., Lau, B., Lo, W.-L., Donermeyer, D.L., Allen, P.M., and Nerbonne, J.M. Loss of Navβ4-mediated regulation of sodium currents in Purkinje neurons disrupts firing and impairs motor coordination and balance. Cell Reports 2017: 19: 532-544.
- Hermanstyne, T.D., Granados-Fuentes, D., Mellor, R., Herzog, E.D., and Nerbonne, J.M. Acute knockdown of Kv4.1 modulates neuronal firing rates and clock gene expression in the suprachiasmatic nucleus and disrupts circadian rhythms in behavior. eNeuro 2017: 4: ENEURO.0377-16.2017.
- Chiamvimonvat, N., Chen-Izu, Y., Clancy, C.E., Deschenes, I., Dobrev, D., Heijman, J., Izu, L., Qu, Z., Ripplinger, C.M., Vandenberg, J.I., Weiss, J.N., Koren, G., Banyasz, T., Grandi, E., Sanguinetti, M.C., Bers, D.M., and Nerbonne, J.M. Potassium currents in the heart: Functional roles in repolarization, arrhythmia and therapeutics. Journal of Physiology 2017: 595: 2229-2252.
- Yang, K.-C., and Nerbonne, J.M. Mechanisms contributing to myocardial potassium diversity, regulation and remodeling. Trends in Cardiovascular Medicine 2016: 26: 209-218.
- 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 2015: 35: 6752-6769.
- 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 2014: 129:1009-1021.
- 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) subunit is required for the generation of native myocardial fast transient outward K+ currents. Journal of Physiology 2013: 591: 4149-4166.
- 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 2010: 30: 13644-13655.
- 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 2008: 102: 1406-1415.
- Nerbonne, J.M., and Kass, R.S. Molecular physiology of cardiac repolarization. Physiological Reviews 2005: 85: 1205-1253.