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Matthew C. Trudeau, PhD

Academic Title:

Associate Professor

Primary Appointment:

Physiology

Location:

660 West Redwood St. HH 503

Phone (Primary):

410-706-5551

Fax:

410-706-8341

Education and Training

I was a graduate student at the University of Wisconsin-Madison with Dr. Gail Robertson from 1993-1998. While there I characterized the molecular and biophysical properties of a voltage-gated ion channel (HERG) that plays a role in repolarization of the cardiac action potential. Mutations in this potassium channel gene are associated with an inherited cardiac arrhythmia (the Long QT syndrome). I was a postdoctoral fellow with Dr. Bill Zagotta at the University of Washington and Howard Hughes Medical Institute in Seattle from 1998 to 2004. My work there focused on the molecular physiology of cyclic nucleotide-gated (CNG) ion channels and their role in an inherited form of vision loss (retinitis pigmentosa) and the mechanism of their modulation by Ca2+-calmodulin. I joined the Department of Physiology as an Assistant Professor in 2004.

Dr. Trudeau is the recipient of the 2014 Paul F. Cranefield Award from the Council of the Society of General Physiologists.

Highlighted Publications

Gustina, A.S. and Trudeau, M.C. (2013) The eag domain regulates hERG channel inactivation via a direct interaction. The Journal of General Physiology, 141(2), 229-241. PMCID: PMC3557309.

Brelidze, T.I., Gianulis, E.G., DiMaio, F., Trudeau, M.C. and Zagotta, W.N. (2013) Structure of the C-terminal region of an ERG channel and functional implications. Proceedings of the National Academy of Sciences, USA. 110(28), 11648-11653. PMCID: PMC3710865

Gianulis E.C., Liu Q., Trudeau M.C. (2013) Direct interaction of eag domains and cyclic nucleotide-binding homology domains regulate deactivation gating in hERG channelsJ Gen Physiol. 2013 Oct;142(4):351-366.PMCID: PMC3787778

Jones, D.K., Liu, F., Vaidyanathan, Eckhardt, L.L., Trudeau, M.C. and Robertson, G.A. (2014) hERG 1b is Critical for Human Cardiac Repolarization. Proceedings of the National Academy of Science, USA. 111(50) 18073-18077. PMCID: PMC4273358.

Liu, Q-N and Trudeau M.C. (2015)  Eag Domains Regulate LQT Mutant hERG Channels in Human Induced Pluripotent Stem Cell-Derived CardiomyocytesPLoS ONE10 (4) e0123951. PMCID: PMC4414485.

McNally, B.A., Pendon, Z., Trudeau, M.C. (2017) hERG1a and hERG1b potassium channel subunits directly interact and preferentially form heteromeric channelsJ Biol Chem. Dec 29;292(52):21548-21557. PMCID: PMC5766944

Jones, D.K., Johnson, A., Roti Roti, E.C., Liu, F., Uelmen, R., Ayers, R.A., Baczko, I., Tester, D.J., Ackerman, M.J., Trudeau, M.C., Robertson, G.A.  (2018)  Localization and functional consequences of a direct interaction between TRIOBP-1 and hERG/KCNH2 proteins in the heart.  J Cell Sci.  Mar 22;131(6).  PMCID: PMC5897710

 

Additional Publication Citations

Trudeau, M.C., Warmke, J.W., Ganetzky, B. and Robertson, G.A. (1995) HERG, a human inward rectifier in the voltage-gated potassium channel familyScience. 269, 92-95.

Trudeau, M.C., Titus, S.A., Branchaw, J.L., Ganetzky, B. and Robertson, G.A. (1999) Functional analysis of a mouse brain Elk-type K+ channelJournal of Neuroscience. 19, 2906-2918.

Trudeau, M.C. and Zagotta, W.N. (2002) An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated channels and is disrupted in an inherited form of blindnessNeuron. 34, 197-207.

Trudeau, M.C. and Zagotta, W.N. (2002) Mechanism of calcium/calmodulin inhibition of rod cyclic nucleotide-gated channelsProc. Natl. Acad. Sci. USA, 99(12), 8424-8429.

Trudeau, M.C. and Zagotta, W.N. (2003) Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channelsJournal of Biological Chemistry. 278, 18705-18708.

Trudeau, M.C. and Zagotta, W.N. (2004) Dynamics of Ca2+-calmodulin dependent inhibition of rod cyclic nucleotide-gated channels measured by patch-clamp fluorometryJournal of General Physiology.  124(3), 211-223.  PMCID: PMC2233886

Shepard P.D. and Trudeau, M.C.  (2008) Emerging roles for ether á go-go related gene potassium channels in the brain. .Journal of Physiology, Oct 15;586 (Pt 20):4785-6. PMCID: PMC2614064

Gustina, A.S. and Trudeau, M.C. (2009)  A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channelsProceedings of the National Academy of Sciences. 106:13082-13087. PMCID: PMC2722319

Gustina, A.S. and Trudeau, M.C. (2011) hERG potassium channel gating is mediated by N- and C-terminal region interactionsJournal of General Physiology, 137, 315-325. PMCID: PMC3047612

Gianulis, E.C. and Trudeau, M.C. (2011) Rescue of aberrant gating by a genetically-encoded PAS domain in several long QT syndrome mutant human ether á go-go related gene potassium channelsJournal of Biological Chemistry, 286, 22160-22169. PMCID: PMC3121360

Trudeau, M.C., Leung, L.M., Roti Roti, E., and Robertson, G.A. (2011) hERG1a N-terminal eag domain-containing polypeptides regulate homomeric hERG1b and heteromeric hERG1a/hERG1b channels: A possible mechanism for Long QT syndromeJournal of General Physiology, 138(6), 581-592. PMCID: PMC3226966

Gustina, A.S. and Trudeau, M.C. (2012) hERG Potassium Channel Regulation by the N-terminal eag domainCellular Signalling.

Trudeau, M.C. (2012) Unlocking the mechanisms of HCN channel gating with locked-open and locked-closed channels.The Journal of General Physiology, 140(5), 457-461. PMCID: PMC3483117.

Gustina, A.S. and Trudeau, M.C. (2013) The eag domain regulates hERG channel inactivation via a direct interaction.The Journal of General Physiology, 141(2), 229-241. PMCID: PMC3557309.

Brelidze, T.I., Gianulis, E.G., DiMaio, F., Trudeau, M.C. and Zagotta, W.N. (2013) Structure of the C-terminal region of an ERG channel and functional implicationsProceedings of the National Academy of Sciences, USA. 110(28), 11648-11653. PMCID: PMC3710865

Research Interests

Ion channels are integral membrane proteins that control the electrical properties that underlie signaling in the nervous system. Ion channels respond to a wide variety of stimuli, including temperature, mechanical force, transmembrane voltage and chemical messengers. Upon activation, channels undergo conformational changes that control the passage of ions through the channel pore and across the cell membrane, which in turn controls membrane voltage and ultimately neuronal signaling. In this way, channels transduce local sensory and electrochemical input into the electrical signals used by the nervous system. Detailed understanding of the basic properties of ion channels, including the molecular rearrangements associated with channel opening and closing, the rearrangements resulting from the actions of modulatory factors and the steps controlling channel density at the cell surface are necessary to understand the electrical properties of cells. In addition, such understanding lends insight into how inherited defects in channel genes result in disease states. To these ends, my lab investigates the molecular specializations underlying ion channel function in potassium channels activated by voltage and cation channels activated by intracellular cyclic nucleotides. The lab employs a variety of techniques to explore these questions including molecular biology, biochemistry, electrophysiology and fluorescence-based imaging.

Awards and Affiliations

  • 2008 Helen Pumphrey Denit Trust Award
  • 2011 National Alliance for Research in Schizophrenia and Depression, Young Investigator Award
  • 2014 Paul F. Cranefied Award, Society of General Physiologists/Journal of General Physiology
  • 2014-present Director and co-PI, T32 Training Program in Integrative Membrane Biology
  • 2015 National Institutes of Health (NIH) Biophysical Studies of Receptors, Channels and Transporters, Special Emphasis Panel, Member
  • 2015 Council Member, Society of General Physiologists
  • 2015 Editorial Advisory Board Member, Journal of General Physiology
  • 2015 Zheng, J. and Trudeau, M.C., Editors, Handbook of Ion Channels. Taylor and Francis, CRC press.
  • 2016 National Institutes of Health (NIH) Ion Channels and Synapses, Special Emphasis Panel, Member
  • 2016 Panelist, University of California-Davis Cardiovascular Symposium.
  • 2017 Secretary/Treasurer Membrane Biophysics Subgroup, Biophysical Society

Grants and Contracts

Ashley Johnson, Ph.D., Postdoctoral Fellow, F32 HL131189-01 "The F-actin binding protein TRIOBP-1 regulates hERG K+ channels"

09/01/18-08/30/23 (Subcontract to Trudeau Lab) PI: Bentley
Title: “Maryland Center for Excellence in Regulatory Science and Innovation (M-CERSI)”
U01 FS005946 Food and Drug Administration

08/01/18-07/31/23 (Trudeau subaward is for two years) PI: Robertson
Title: “Allosteric Regulation of KCNH channels”
The goal of this work is to study allosteric regulation of gating in in KCNH family channels including with a major focus on EAG channels. The Trudeau subcontract is to use UV light to photoactivate and cross-link amino acids to study KCNH channel gating
NIH/NHLBI  R01 2R01NS081320-05A1 

07/01/18-06/30/23 PI: Matthew C. Trudeau
Title: “Training Program in Integrative Membrane Biology”
The major goals of this project are to train outstanding graduate students in the theory and practice of membrane biology
NIH/NIGMS T32 GM008181-31