Thanos Tzounopoulos

  • Director, Pittsburgh Hearing Research Center
  • Endowed Professor and Vice Chair of Research, Department of Otolaryngology

Current Research

My research has been focused on the synaptic and intrinsic properties and plasticity of brain circuits and neurons. We have discovered novel synaptic and intrinsic mechanisms in the auditory brainstem and cortex, as well as their effects during normal and pathological auditory processing in animal models of hearing loss and tinnitus. Moreover, we are currently pursuing drug discovery and development for tinnitus and hearing loss.

Podcast and video featuring our basic science and drug development work on tinnitus.


Selected Recent Publications

A CRE/DRE dual recombinase transgenic mouse reveals synaptic zinc-mediated thalamocortical neuromodulation
Science Advances    In Press
Stylianos Kouvaros, Brandon Bizup, Oscar Solis, Manoj Kumar, Emilya Ventriglia, Fallon P. Curry, Michael Michaelides*, Thanos Tzounopoulos*
*Corresponding authors

A Genetically Encoded Far-Red Fluorescent Indicator for Imaging Synaptically-Released Zn2+
Science Advances    March 1, 2023
Tianchen Wu, Manoj Kumar, Jing Zhang, Zhengyu Zhao, Mikhail Drobizhev, Mason McCollum, Charles T. Anderson, Ying Wang, Antje Almeida, Xiaodon, Tian, Yiyu Zhang, Thanos Tzounopoulos*, Hui-wang Ai*
These authors contributed to this work equally
*Corresponding authors

A role for KCNQ channels on cell-type-specific plasticity in mouse auditory cortex after peripheral damage
Journal of Neuroscience    March 29, 2023
Amanda Henton, Yanjun Zhao, and Thanos Tzounopoulos

Neuromodulatory Mechanisms Underlying Contrast Gain Control in Mouse Auditory Cortex
Journal of Neuroscience    Jun 3, 2022
Patrick Cody, Thanos Tzounopoulos

Development of an Automated Screen for Kv7.2 Potassium Channels and Discovery of a New Agonist Chemotype
Bioorg Med Chem Lett    Jun 4, 2022
Ciria C. Hernandez, Rahilla A. Tarfa, Jose Miguel I Limcaoco, Ruiting Liu, Pravat Mondal, Clare Hill, R. Keith Duncan, Thanos Tzounopoulos, Corey R.J. Stephenson, Matthew J. O'Meara, Peter Wipf

ZnT1 is a Neuronal Zn2+/Ca2+ Exchanger
Cell Calcium     Nov 23, 2021
Noa Gottesman, Hila Asraf, Milos Bogdanovic, Israel Sekler, Thanos Tzounopoulos, Elias Aizenman, Michal Hershfinkel

What's the Buzz? The Neuroscience and the Treatment of Tinnitus
Physiological Reviews     Oct 1, 2021
Amanda Henton, Thanos Tzounopoulos

Transient Delivery of KCNQ2/3-Specific Channel Activator One Week after Noise Trauma Mitigates Noise-Induced Tinnitus
J Assoc Res Otolaryngol     Apr 22, 2021
Laura Marinos, Stylianos Kouvaros, Brandon Bizup, Bryce Hambach, Peter Wipf, Thanos Tzounopoulos

The Function and Regulation of Zinc in the Brain
Neuroscience     Jun 3, 2021
Rebecca F. Krall, Tzounopoulos Thanos, Aizenman Elias

Synaptic Zinc Inhibition of NMDA Receptors Depends on the Association of GluN2A with the Zinc Transporter ZnT1
Science Advances     Jun 3, 2020
Rebecca F. Krall, Aubin Moutal, Matthew B. Phillips, Hila Asraf, Jon W. Johnson, Rajesh Khanna, Michal Hershfinkel, Elias Aizenman, Thanos Tzounopoulos

Mechanisms Underlying Long-Term Synaptic Zinc Plasticity at Mouse Dorsal Cochlear Nucleus Glutamatergic Synapses
Journal of Neuroscience    May 20, 2020
Nathan W. Vogler, Vincent M. Betti, Jacob M. Goldberg, Thanos Tzounopoulos

Synaptic Zinc Enhances Inhibition Mediated by Somatostatin, but not Parvalbumin, Cells in Mouse Auditory Cortex
Cereb Cortex    Jun 1 2020
Stylianos Kouvaros, Manoj Kumar, Thanos Tzounopoulos

Towards a Mechanistic-Driven Precision Medicine Approach for Tinnitus
J Assoc Res Otolaryngol     Apr 20, 2019
Thanos Tzounopoulos, Carey Balaban, Lori Zitelli, Catherine Palmer

Fine Control of Sound Frequency Tuning and Frequency Discrimination Acuity by Synaptic Zinc Signaling in Mouse Auditory Cortex
Journal of Neuroscience     Jan 30, 2019
Manoj Kumar, Shanshan Xiong, Thanos Tzounopoulos, Charles T. Anderson

Photoactivatable Sensors for Detecting Mobile Zinc
J Am Chem Soc     Feb 14, 2018
Jacob M. Goldberg, Fang Wang, Chanan D. Sessler, Nathan W. Vogler, Daniel Y. Zhang, William H. Loucks, Thanos Tzounopoulos, Stephen J. Lippard

Cell-specific Gain Modulation by Synaptically Released Zinc in Cortical Circuits of Audition
Elife     Sep 9, 2017
Charles T. Anderson*, Manoj Kumar*, Shanshan Xiong, Thanos Tzounopoulos
*Equal contribution

Context-Dependent Modulation of Excitatory Synaptic Strength by Synaptically Released Zinc
eNeuro     Mar 3, 2017
Bopanna I. Kalappa, Thanos Tzounopoulos

Cell-Specific Cholinergic Modulation of Excitability of Layer 5B Principal Neurons in Mouse Auditory Cortex
Journal of Neuroscience     Aug 10, 2016
Ankur Joshi, Bopanna I. Kalappa, Charles T. Anderson, Thanos Tzounopoulos

Synthesis and Evaluation of Potent KCNQ2/3-specific Channel Activators
Mol Pharmacol     Mar 22, 2016
Manoj Kumar, Reed N, Liu R, Elias Aizenman, Peter Wipf, Thanos Tzounopoulos

Noise-Induced Plasticity of KCNQ2/3 and HCN Channels Underlies Vulnerability and Resilience to Tinnitus
Elife     Aug 27, 2015
Shuang Li, Bopanna I. Kalappa, Thanos Tzounopoulos

Potent KCNQ2/3-specific Channel Activator Suppresses in vivo Epileptic Activity and Prevents the Development of Tinnitus
Journal of Neuroscience     Jun 10, 2015
Bopanna I. Kalappa, Heun Soh, Kevin Duignan, Takeru Furuya, Scott Edwards, Anastassios V.Tzingounis, Thanos Tzounopoulos

Modulation of Extrasynaptic NMDA Receptors by Synaptic and Tonic Zinc
Proc Natl Acad Sci USA (PNAS)     May 6, 2015
Charles T. Anderson, Robert J. Radford, Melissa L. Zatsrow, Daniel Y. Zhang, Ulf-Peter Apfel, Stephen J. Lippard, Thanos Tzounopoulos

Tonic Non-Vesicular Zinc Inhibits Spontaneous Neuronal Firing in Dorsal Cochlear Nucleus Principal Neurons by Enhancing Tonic Glycinergic Inhibition
Neurobiology of Disorder     Mar 18, 2015
Tamara Perez-Rosello, Charles T. Anderson, Cindy Ling, Thanos Tzounopoulos

Cell-specific, Activity-dependent Fractionation of Layer 2/3→5B Excitatory Signaling in Mouse Auditory Cortex
Journal of Neuroscience     Feb 18, 2015
Ankur Joshi, Jason Middleton, Charles T. Anderson, Katharine Borges, Benjamin Suter, Gordon M. G. Shepherd, Thanos Tzounopoulos


News and Views Articles on Our Work

UPMC Physician Resources (2022): Discovering a Drug Therapy for Tinnitus
University of Pittsburgh Pittwire (2021): A Pitt Scientist is Striving to Quiet the Ringing in Veterans’ Ears
UPMC/University of Pittsburgh (2021): RL-81 Could Be Promising Drug Candidate for Noise-Induced Tinnitus
Biochemistry (2018): New Tools Uncover New Functions for Mobile Zinc in the Brain
Elife (2017): A New Role for Zinc in the Brain
NSF (2017): NSF-BSF-supported Study Turns Up the Volume on the Mysteries of Sound
University of Pittsburgh (2016): Sound Investment: Pitt, Allergan to Collaborate on Tinnitus Research
UPMC/University of Pittsburgh (2016): Pitt Team Redesigns Epilepsy Drug to Increase Potency and Specificity, Reduce Side Effects
Molecular Pharmacology Highlights (2016): MOL Highlight: Synthesis and Evaluation of Potent KCNQ2/3-Specific Channel Activators
Expert Opin Ther Targets (2015): Potassium channels as promising new targets for pharmacologic treatment of tinnitus: Can internet-based "crowd sensing" initiated by patients speed up the transition from bench to bedside?
UPMC/University of Pittsburgh (2015): Pitt Team Identifies Cause of Resilience to Tinnitus, Drugs That Can Reduce Chance of Developing the Debilitating Condition
Pittsburgh Post-Gazette (2015): University of Pittsburgh finds zinc to be important in brain signaling
Science and Technology Daily (2015): New Drug to Quiet Brain, Relieving Epilepsy and Tinnitus
SciFluor (2015): Novel KCNQ2/3 activator
The Eye and Ear Foundation of Pittsburgh (2015): Stop The Ringing
The Science Business eXchange(2013): Potassium channel Kv7.2 (KCNQ2); KCNQ3
The Hearing Journal (2013): Noise-Induced Tinnitus Linked to Lower Potassium Channel Activity
Εθνικός Κήρυξ (2013): Θα σώσει εκατομμύρια η έρευνα του Θάνου Τζουνόπουλου
NIH/NIDCD (2013): Grantee news, Pitt team finds biologic mechanism that causes noise-induced tinnitus and drug that can prevent it.
Journal of Neuroscience (2013): This Week in The Journal
Department of Defense (2013): Mechanisms Underlying Noise-Induced Tinnitus
Wall Street Journal (2011): Finding the Pathways to a Cause of Tinnitus
Voice of America (2011): Research Shows Tinnitus May Affect Brain Responses
National Public Radio (2011): Study Finds Cause for Tinnitus
Science Daily (2011): Tinnitus Caused by Too Little Inhibition of Brain Auditory Circuits