Update Your ProfileAcademic Title:
Professor
Primary Appointment:
Pharmacology & 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
Zheng, J. and Trudeau, M.C., Editors, Textbook of Ion Channels. Taylor and Francis, CRC Press, to be published in 2023.
Johnson, A.A., Crawford, T.R., Trudeau, M.C. (2022) The N-linker region of hERG1a upregulates hERG1b potassium channels. J Biol Chem. Sep;298(9):102233. Epub 2022 Jul 5. PMCID: PMC9428852
Codding, S.J., Johnson, A.A. and Trudeau, M.C. (2020) Gating and Regulation of KCNH (ERG, EAG and ELK) channels by intracellular domains. Channels (Austin). (1):294-309. 2020. PMCID: PMC7515569.
Codding, S.J. and Trudeau, M.C. (2019) The hERG potassium channel intrinsic ligand regulates N- and C-terminal interaction and channel closure. J. Gen. Physiol. 151(4)478-488. PMCID: PMC6445578
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
McNally, B.A., Pendon, Z., Trudeau, M.C. (2017) hERG1a and hERG1b potassium channel subunits directly interact and preferentially form heteromeric channels. J Biol Chem. Dec 29;292(52):21548-21557. PMCID: PMC5766944
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.
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 channels. J Gen Physiol. 2013 Oct;142(4):351-366.PMCID: PMC3787778
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
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.
Additional Publication Citations
Harley, C.A., Bernardo-Seisdedos, G., Stevens-Sostre, W.A., Jones, D.K., Azevedo, M.M., Sampaio, P., Lorga-Gomes, M., Trudeau, M.C., Millet, O., Robertson, G.A., Morais-Cabral, J.H. (2021) Conformation-sensitive antibody reveals an altered cytosolic PAS/CNBh assembly during hERG channel gating. Proc Natl Acad Sci USA. 2021 Nov 2;118(44):e2108796118. PMCID: PMC8612226
Jones, D.K.*, Johnson, A.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. Journal of Cell Science. Mar 22;131(6). PMCID: PMC5897710.
Liu, Q-N and Trudeau M.C. (2015) Eag Domains Regulate LQT Mutant hERG Channels in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. PLoS ONE10 (4) e0123951. PMCID: PMC4414485.
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
Gustina, A.S. and Trudeau, M.C. (2012) hERG Potassium Channel Regulation by the N-terminal eag domain. Cellular 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. (2011) hERG potassium channel gating is mediated by N- and C-terminal region interactions. Journal 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 channels. Journal 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 syndrome. Journal of General Physiology, 138(6), 581-592. PMCID: PMC3226966
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 channels. Proceedings of the National Academy of Sciences. 106:13082-13087. PMCID: PMC2722319
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
Trudeau, M.C. and Zagotta, W.N. (2004) Dynamics of Ca2+-calmodulin dependent inhibition of rod cyclic nucleotide-gated channels measured by patch-clamp fluorometry. Journal of General Physiology. 124(3), 211-223. PMCID: PMC2233886
Trudeau, M.C. and Zagotta, W.N. (2003) Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channels. Journal of Biological Chemistry. 278, 18705-18708.
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 blindness. Neuron. 34, 197-207.
Trudeau, M.C. and Zagotta, W.N. (2002) Mechanism of calcium/calmodulin inhibition of rod cyclic nucleotide-gated channels. Proc. Natl. Acad. Sci. USA, 99(12), 8424-8429.
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+ channel. Journal of Neuroscience. 19, 2906-2918.
Trudeau, M.C., Warmke, J.W., Ganetzky, B. and Robertson, G.A. (1995) HERG, a human inward rectifier in the voltage-gated potassium channel family. Science. 269, 92-95.
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
- 2022 Faculty Excellence in Postdoctoral Mentorship Award, University of Maryland School of Medicine
- 2022 Co-Chair, Society of General Physiologists Meeting 2022, Woods Hole, MA
- 2017 Secretary/Treasurer Membrane Biophysics Subgroup, Biophysical Society
- 2016 National Institutes of Health (NIH) Ion Channels and Synapses, Special Emphasis Panel, Member
- 2016 Panelist, University of California-Davis Cardiovascular Symposium.
- 2015 Zheng, J. and Trudeau, M.C., Editors, Handbook of Ion Channels. Taylor and Francis, CRC press.
- 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
- 2014-present Director and co-PI, T32 Training Program in Integrative Membrane Biology
- 2014 Paul F. Cranefied Award, Society of General Physiologists/Journal of General Physiology
- 2011 National Alliance for Research in Schizophrenia and Depression, Young Investigator Award
- 2008 Helen Pumphrey Denit Trust Award
Grants and Contracts
06/30/2021-06/30/2023
Title: "Using non-canonical amino acids to repair hERG LQT2 mutants in hiPSC-CMs"
Maryland Stem Cell Research Fund (MSCRF) - Discovery Research Grant 5621
04/01/2019-03/31/2023 - NCE through 2/28/2024
Title: "Regulatory and Functional Mechanisms in hERG Ion Channels"
The goal of the work in this proposal is determine new protein interaction mechanisms that regulate hERG current in heterologous expression systems and native systems, including stem-cell derived cardiomyocytes, and use this knowledge to inform disease mechanisms and mechanisms for reversing disease phenotypes.
NIH/NIGMS 1R01GM127523-01A1
01/01/2019-12/30/2022 (PI: Trudeau) - NCE through 12/30/2023
Title: "Conformational Dynamics of hERG Ion Channels"
The major focus of this grant is to determine the biophysics of gating (opening and closing) in hERG potassium channel domains using spectroscopy to measure dynamics and electrophysiology to measure function.
NIH/NIGMS 1R01GM130701-01
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