Current Research
In a modernized society, where it is becoming difficult to escape loud noises, exposure to loud noises is the leading cause of hyperacusis and tinnitus, the highly debilitating hearing disorders characterized by hyperexcitability of the brain cells. Hyperacusis, which is diagnosed as painful sensitivity to everyday sounds, affects 10-15% of people. Tinnitus, which is diagnosed as the perception of phantom sounds, affects about 15-20% of people. Despite the high prevalence and debilitating consequences of hyperacusis and tinnitus, treatment options are limited to hearing prosthetics with no pharmacotherapeutic options. To aid in the development of prevention and treatment options for noise-induced hyperexcitability hearing disorders, it is imperative to decipher the molecular and cellular signaling mechanisms underlying the hyperexcitability of brain cells after loud-noise exposure.
In my research program, to mechanistically develop and test the pharmacotherapy for noise-induced hyperexcitability disorders, we are identifying the signaling mechanisms underlying the brain cells' hyperexcitability after loud-noise exposure at molecular-, cellular-, and behavioral levels. To achieve our research goals, we employ in vivo acute and longitudinal two-photon Ca2+ imaging of distinct neuronal brain cell-types in awake mice, operant behavior, chemogenetics, optogenetics, inducible conditional knockout mice, and pharmacological approaches.
If you are interested in joining our research team, please contact me at Mak328@Pitt.edu.
Selected Recent Publications
Cortical Zinc Signaling Is Necessary for Changes in Mouse Pupil Diameter That Are Evoked by Background Sounds with Different Contrasts
Journal of Neuroscience March, 2024
Patrick Cody, Manoj Kumar, Thanos Tzounopoulos
Cell-type-specific plasticity of inhibitory interneurons in the rehabilitation of auditory cortex after peripheral damage
Nature Communications July, 2023
Manoj Kumar*, Gregory Handy, Stylianos Kouvaros, Yanjun Zhao, Lovisa Ljungqvist Brinson, Eric Wei, Brandon Bizup, Brent Doiron, and Thanos Tzounopoulos*
*Corresponding Authors
A CRE/DRE dual recombinase transgenic mouse reveals synaptic zinc-mediated thalamocortical neuromodulation
Science Advances June, 2023
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, 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
Synaptic Zinc Enhances Inhibition Mediated by Somatostatin, but not Parvalbumin, Cells in Mouse Auditory Cortex
Cerebral Cortex Jun 1, 2020
Stylianos Kouvaros, Manoj Kumar, and Thanos Tzounopoulos
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, and Thanos Tzounopoulos and Charles T. Anderson
Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition
eLife Sep 9, 2017
Charles T Anderson*, Manoj Kumar*, Shanshan Xiong and Thanos Tzounopoulos
*equal contribution
A Single Amino Acid Residue at Transmembrane Domain 4 of the α Subunit Influences Carisoprodol Direct Gating Efficacy at GABAA Receptors
Journal of Pharmacology and Experimental Therapeutics Jun 22, 2017
Manoj Kumar, Manish Kumar, John M Freund, Glenn H Dillon
Synthesis and Evaluation of Potent KCNQ2/3-specific Channel Activators
Molecular Pharmacology Jun 8, 2016
Manoj Kumar, Nicholas Reed, Ruiting Liu, Elias Aizenman, Peter Wipf, Thanos Tzounopoulos
Assessment of subunit-dependent direct gating and allosteric modulatory effects of carisoprodol at GABA receptors
Neuropharmacology Apr 18, 2015
Manoj Kumar, Lorie A González, Glenn H Dillon
Funding
HEARING HEALTH FOUNDATION
KCNQ2/3 potassium channel activator mitigate noise-trauma-induced hypersensitivity to sounds in mice
10/1/2024 – 9/30/2025
Role (PI)
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
Cortical neuromodulatory mechanisms underlying adaptation and plasticity
09/1/2023 – 8/31/2028
Role (Co-I)
HEARING HEALTH FOUNDATION
Signaling Mechanisms of Auditory Cortex Plasticity After Noise-Induced Hearing Loss
10/1/2021 – 9/30/2023
Role (PI)
EYE AND EAR FOUNDATION OF PITTSBURGH
Albert C. Muse Endowed Research Award
04/1/2022 - 03/31/2023
Role (PI)
NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
Fluorescent Indicators for Imaging Synaptic Zinc in Cortical Sound Processing
10/1/2022 – 9/30/2026
Role (Co-I)