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Faculty Affairs: Faculty Interests Database Manuel L. Covarrubias, MD, PhD

Thomas Jefferson University,Jefferson Medical College,Department of Neuroscience
Appointed: 2004
Mailing Address Contact Information
900 Walnut Street
Philadelphia, Pennsylvania 19107
United States
Phone: (215) 503-4341
M.D., National University of Mexico, 1978

Ph.D., National University of Mexico, Chemistry, 1980

Postdoctoral Training:

Max-Planck-Institut fuer Ernaehrungsphysiologie, Dortmund, Germany

Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO

Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO
Expertise and Research Interests

Voltage-gated potassium channels; molecular mechanisms underlying function, regulation and interactions with


The research in my laboratory focuses on voltage-gated potassium channels expressed in brain and heart. We
investigate the molecular mechanisms governing the function and regulation of these ion channels. These
studies can impact our understanding of neuronal plasticity, epilepsy, chronic pain, arrhythmias, anesthesia and
alcohol intoxication. Furthermore, they may unveil potential drug-targets. The research platform of our work is
based on a modern multidisciplinary approach, which applies electrophysiology, molecular biology, biochemistry,
pharmacology and mathematical modeling.

Other Expertise

Physiological Sciences Study Section (NIH). 1995-1996.

NIH/MBPP (Membrane Biology & Protein Processing Study Section. Regular member from 2005 - 2008.

NIH. Ad hoc grant reviewer

NIH. Intramural Program reviewer, 2011

National Science Foundation. Ad hoc reviewer, 1995, 2008.

Medical Research Council, UK. Ad hoc reviewer, 2007.

Manuscript Reviewer (since 1991): J. Biol. Chem.; J. Gen. Physiol.; Biophys. J.; J. Physiol. (London); Am. J.
Physiol. (Cell Physiol.); FEBS Lett.; Proc. Nat. Acad. Sci. USA; J. Neurosci.; Mol. Cell Neurosci; Nature Chem.


Faculty member of the Ph.D. programs in Neuroscience, Molecular Physiology and Biophysics, Biochemistry and
Molecular Pharmacology, and Cell and Developmental Biology at Thomas Jefferson University.

Medical School Courses: Neuroscience (MCBM, ID150). 2010-

Course director of NS700 (Cellular Neurophysiology). 2014-

Director of the Graduate Program in Neuroscience. 2013-


Tapan B. Vyas (1992-1995); Laura Escobar (1994-1995); Henry H. Jerng (1993-1998); Mohammad Shahidullah
(1997-2003); Edward J. Beck (1997-2001); Maria T. Pacheco-Cano (1998-1999); Ricardo Hernandez-Pineda
(1999-2000); Carmen A. Rocha (2001-2003); Benjamin Kaplan (2002-2004); Thanawath Harris (2002-2008 );
Guangyu Wang (2003-2007); Kevin Dougherty (2004-2008); Jose A. De Santiago-Castillo (2006-2008); Jeffrey
Fineberg (2009-2013 ); Annika Fitzpatrick (2009-2013 ); David Ritter (2009-2013 ); Benjamin Zemel (2012- );
Tanziyah Muqeem (2014- ); Elaine Yang (2014- ); Shelly Jones (2013- ).
potassium channel; voltage-gated potassium channel; K channel; Kv4 potassium channel; KChIP; DPP6; somatodendritic potassium channels; alkanol; anesthetic; channel inactivation; neuronal channel; cardiac channel; electrophysiology; patch-clamp
  • SELECTED (2004- )
  • Jerng, H.H., Pfaffinger, P.J. and Covarrubias, M. (2004). Molecular Physiology and Modulation of the
  • Somatodendritic A-type Potassium Channel. Molecular and Cellular Neuroscience 27: 343-369.
  • Wang, G., Shahidullah, M., Rocha, C.A., Strang, C., Pfaffinger, P.J. and Covarrubias, M. (2005). Functionally
  • active T1-T1 interfaces revealed by the accessibility of intracellular thiolate groups in Kv4 channels. J. Gen.
  • Physiol. 126:55-69.
  • Wang, G. and Covarrubias, M. (2006). Voltage-dependent gating rearrangements in the intracellular T1-T1
  • interface of a Kv channel. J. Gen. Physiol. 127:391-400.
  • Bhattacharji, A. Kaplan, B., Harris, T., Qu, X., Germann, M. W. and Covarrubias, M. (2006). The concerted
  • contribution of the S4-S5 linker and the S6 segment to the modulation of a Kv channel by 1-alkanols. Mol.
  • Pharm. 70:1542-54.
  • Fawcett, G.L., Santi, C., Butler, A., Harris, T., Covarrubias, M. and Salkoff, L. (2006). Mutant Analysis of the Shal
  • (Kv4) voltage-gated fast transient K+ channel in C. elegans. J. Biol. Chem. 281:30725-35.
  • Dougherty, K. and Covarrubias, M. (2006). A dipeptidyl aminopeptidase protein remodels gating charge
  • dynamics in Kv4.2 channels. J. Gen. Physiol. 128:745-53.
  • Wang, G., Strang, C., Pfaffinger, P.J. and Covarrubias, M. (2007). Zn++dependent redox switch in the
  • intracellular T1-T1 interface of a Kv4 channel. J. Biol. Chem. 282:13637-13647.
  • Rojas, P., Garst-Orozco, J., Baban, B., De Santiago-Castillo, J.A., Covarrubias, M. and Salkoff, L. (2008).
  • Cumulative activation of a voltage-dependent potassium channel. J. Neurosci. 28:757-765.
  • Kaulin, Y.A., De Santiago-Castillo, J.A., Rocha, C.A. and Covarrubias, M. (2008). Mechanism of the modulation
  • of Kv4.3:KChIP1 channels by elevated external K+. Biophys. J. 94:1241-1251.
  • Dougherty, K., De Santiago-Castillo, J.A. and Covarrubias, M. (2008). Gating charge immobilization in Kv4.2
  • channels: the basis of closed-state inactivation. J. Gen. Physiol. 131:257-73.
  • Amarillo, Y. De Santiago-Castillo, J.A., Dougherty, K., Kwon, E., Covarrubias, M. and Rudy, B. (2008). Ternary
  • Kv4.2 channels recapitulate voltage-dependent inactivation kinetics of A-type K+ channels in cerebellar granule
  • neurons. J. Physiol. (London) 586.8:2093-2106.
  • Covarrubias, M., Bhattacharji, A., De Santiago-Castillo, J.A., Dougherty, K., Kaulin, Yu. A., Ratanadilok Na
  • Phuket, T. and Wang, G. (2008). The Neuronal Kv4 Channel Complex (peer-reviewed mini-review article by
  • invitation). Neurochem. Res. 33:1558-1567.
  • Schwenk, J., Zolles, G., Kandias, N.G., Neubauer, I., Kalbacher, H., Covarrubias, M., Fakler, B. and Bentrop, D.
  • (2008). NMR analysis of KChIP4a reveals structural basis for the control of surface expression of Kv4 channel
  • complexes. J. Biol. Chem. 283:18937-18946.
  • Kaulin, Y., De Santiago-Castillo, J.A., Nadal., M., Rudy, B. and Covarrubias, M. (2009). The dipeptidyl-
  • peptidase-like-protein DPP6 determines the unitary conductance of neuronal Kv4.2 channels. J. Neurosci.
  • 29:3242-3251.
  • Dougherty, K., Tu, L., Deutsch, C. and Covarrubias, M. (2009). The dipeptidyl-aminopeptidase-like protein-6 is an
  • integral voltage sensor interacting b-subunit of neuronal Kv4.2 channels. Channels (Austin) 3:122-128.
  • Ratadanilok Na Phuket, T. and Covarrubias, M. (2009). Kv4 channels underlie the subthreshold-operating A-type
  • K+ current in dorsal root ganglion neurons. Frontiers in Molecular Neuroscience 2:1-14.
  • Jerng H.H., Dougherty K., Covarrubias M., Pfaffinger P.J. (2009). A novel N-terminal motif of dipeptidyl
  • peptidase-like proteins produces rapid inactivation of Kv4.2 channels by a pore-blocking mechanism. Channels
  • (Austin) 3:1-14.
  • Eckenhoff, R., Xi, J., Shimaoka, M., Bhattacharji, A., Covarrubias, M., Dailey, W. (2010). Azi-isoflurane, a
  • photolabel analog of the commonly used inhaled general anesthetic, isoflurane. ACS Chemical Neuroscience
  • 1:139-145.
  • Bhattacharji, A., Klett, N., Go, R.C.V. and Covarrubias, M. (2010). Inhalational anesthetics and n-alcohols share
  • a site of action in the neuronal Shaw2 Kv channel. British J. Pharm. 159:1475-85.
  • De Santiago-Castillo, J.A., Covarrubias, M., Sánchez-Rodríguez, J.E., Perez-Cornejo, P., Arreola, J. (2010).
  • Simulating complex ion channel kinetics with IonChannelLab. Channels (Austin) 4:422-8.
  • Bähring, R. and Covarrubias, M. (2011). Mechanisms of closed state inactivation in voltage-gated ion channels
  • (peer-reviewed Topical Review by invitation) J. Physiol. (London) 589(Pt 3):461-79.
  • Cheng, L., Yung, A., Covarrubias, M., Radice, G. (2011). Cortactin is required for N-cadherin regulation of Kv1.5
  • channel function. J. Biol. Chem. 286:20478-89.
  • Barber, A.F., Liang, Q., Amaral, C., Treptow, W. and Covarrubias, M. (2011). Molecular mapping of general
  • anesthetic sites in a voltage-gated ion channel. Biophys. J. 101:1613-1622.
  • Ritter, D., Ho, C., OLeary, M. and Covarrubias, M. (2012). Modulation of Kv3.4 channel N-type inactivation by
  • protein kinase C shapes the action potential in dorsal root ganglion neurons. J. Physiol. (London) 590:145-161.
  • Fineberg, J.D., Ritter, D.M. and Covarrubias, M. (2012). Modeling-independent elucidation of inactivation
  • pathways in recombinant and native Kv channels. J. Gen. Physiol. 140:513-527.
  • Barber, A.F., Liang, Q. and Covarrubias, M. (2012). Novel activation of Kv channels by sevoflurane. J. Biol.
  • Chem. 287:40425-40432.
  • Zhang, J., Qu, X., Covarrubias, M. and Germann, M.W. (2012). Insight into the modulation of Shaw2 Kv channels
  • by general anesthetics: structural and functional studies of S4-S5 linker and S6 C-terminal peptides in micelles
  • by NMR. Biochem. Biophys. Acta (Biomembranes) 1828:595-601.
  • Barber A.F., Carnevale V., Klein M.L., Eckenhoff R.G., Covarrubias M. (2014). Modulation of voltage-gated Na+
  • channels by sevoflurane involves multiple sites and distinct mechanisms. Proc. Natl. Acad. Sci. 111(18):6726-31.

Last Updated by Manuel Covarrubias, MD, PhD: Wednesday, April 6, 2011 11:51:45 AM

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