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Christopher Ahern, PhD

Professor of Molecular Physiology and Biophysics

Introduction

Our current research focus is on the function and pharmacology voltage-gated sodium channels that drive the rapid upstroke of the action-potential throughout the body. We find motivation in the observation that inherited or acquired functional defects in these integral membrane proteins is associated with cardiac arrhythmia, epilepsy, multiple sclerosis and painful syndromes. In the lab, we work at the interface of membrane biophysics and chemical biology. Our particular expertise is in the synthesis and expression channels harboring tailor made non-natural amino acids and the general application of chemical biological approaches to the study of voltage-gated channels. We have had success in expressing synthetic amino acids in many channel and receptor types for pharmacological studies of ligand and drug interactions as well as structure function relationships.

Current Positions

  • Professor of Molecular Physiology and Biophysics

Education

  • BSc in Chemistry, University of Wisconsin, Madison, Wisconsin
  • PhD in Physiology, University of Wisconsin, Madison, Wisconsin
  • Fellow, American Heart Association
  • Fellow, NIH Cardiovascular Research
  • Fellow, Farber Institute for Neuroscience
  • Postdoctoral Fellow in Physiology, Jefferson Medical College, Philadelphia, Pennsylvania

Graduate Program Affiliations

Center, Program and Institute Affiliations

Research Interests

  • Electro-chemical signaling in animals underlies the basis for mobility, cognition and sensation

Selected Publications

  • Pashkova N, Peterson TA, Ptak CP, Winistorfer SC, Guerrero-Given D, Kamasawa N, Ahern CA, Shy ME, Piper RC. Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy. iScience. 2024 Sep 19;27(11):110989. doi: 10.1016/j.isci.2024.110989. PMID: 39759075; PMCID: PMC11700639.
  • Kuru E, Rittichier J, de Puig H, Flores A, Rout S, Han I, Reese AE, Bartlett TM, De Moliner F, Bernier SG, Galpin JD, Marchand J, Bedell W, Robinson-McCarthy L, Ahern CA, Bernhardt TG, Rudner DZ, Collins JJ, Vendrell M, Church GM. Rapid discovery and evolution of nanosensors containing fluorogenic amino acids. Nat Commun. 2024 Sep 5;15(1):7531. doi: 10.1038/s41467-024-50956-z. PMID: 39237489; PMCID: PMC11377706.
  • Infield DT, Schene ME, Galpin JD, Ahern CA. Genetic Code Expansion for Mechanistic Studies in Ion Channels: An (Un)natural Union of Chemistry and Biology. Chem Rev. 2024 Oct 23;124(20):11523-11543. doi: 10.1021/acs.chemrev.4c00306. Epub 2024 Aug 29. PMID: 39207057; PMCID: PMC11503617.
  • Goodchild SJ, Ahern CA. Conformational photo-trapping in NaV1.5: Inferring local motions at the "inactivation gate". Biophys J. 2024 Jul 16;123(14):2167-2175. doi: 10.1016/j.bpj.2024.04.017. Epub 2024 Apr 24. PMID: 38664963; PMCID: PMC11309974.
  • Schene ME, Infield DT, Ahern CA. Expression and purification of fluorinated proteins from mammalian suspension culture. Methods Enzymol. 2024;696:341-354. doi: 10.1016/bs.mie.2024.01.004. Epub 2024 Jan 23. PMID: 38658087; PMCID: PMC11749373.
  • Blomquist VG, Niu J, Choudhury P, Al Saneh A, Colecraft HM, Ahern CA. Transfer RNA-mediated restoration of potassium current and electrical correction in premature termination long-QT syndrome hERG mutants. Mol Ther Nucleic Acids. 2023 Sep 16;34:102032. doi: 10.1016/j.omtn.2023.102032. PMID: 37842167; PMCID: PMC10568093.
  • Minard AY, Clark CJ, Ahern CA, Piper RC. Beta-subunit-eliminated eHAP expression (BeHAPe) cells reveal subunit regulation of the cardiac voltage-gated sodium channel. J Biol Chem. 2023 Sep;299(9):105132. doi: 10.1016/j.jbc.2023.105132. Epub 2023 Aug 6. PMID: 37544648; PMCID: PMC10506104.
  • Ptak CP, Peterson TA, Hopkins JB, Ahern CA, Shy ME, Piper RC. Homomeric interactions of the MPZ Ig domain and their relation to Charcot-Marie-Tooth disease. Brain. 2023 Dec 1;146(12):5110-5123. doi: 10.1093/brain/awad258. PMID: 37542466; PMCID: PMC10690024.
  • Chen X, Coffman BL, Brindley RL, Galpin JD, Ahern CA, Currie KPM, Smrcka AV, Axelrod D, Anantharam A. Phospholipase C-ε defines a PACAP-stimulated pathway for secretion in the chromaffin cell. J Neuroendocrinol. 2023 Nov;35(11):e13255. doi: 10.1111/jne.13255. Epub 2023 Mar 27. PMID: 36970756; PMCID: PMC10790106.
  • Strege PR, Cowan LM, Alcaino C, Mazzone A, Ahern CA, Milescu LS, Farrugia G, Beyder A. Mechanosensitive pore opening of a prokaryotic voltage-gated sodium channel. Elife. 2023 Mar 13;12:e79271. doi: 10.7554/eLife.79271. PMID: 36912788; PMCID: PMC10038658.