Hearing Loss and Tinnitus Research

• Vice Chair of Clinical and Translational Research
• Chief, Division of Otology/Neurotology
• Professor, Division Chief of Otology & Neurotology
• Director of Faculty Innovation, Office of Innovation and Entrepreneurship
• Director, SPARK Global

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

Our research has been focused on the synaptic physiology and synaptic plasticity of auditory brain circuits and neurons. We have discovered novel synaptic mechanisms in the auditory brainstem, thalamus and cortex, as well as their effects in normal and pathological processing in animal models of hearing loss, tinnitus and hyperacusis. Importantly, we are pursuing drug discovery/development and gene therapy for tinnitus, hyperacusis, and congenital hearing loss.

• Professor of Otology/Neurotology, Director of Global Otolaryngology

Currently using innovative human brain imaging (functional-Near Infrared Spectroscopy; fNIRS) to investigate cross modal plasticity in human auditory cortex pre- and post-cochlear device implant following single-sided deafness. Also using fNIRS to objectify human brain responses (neural correlates) in subjective and somatosensory tinnitus.

•  Assistant Professor, Department of Otolaryngology and the Pittsburgh Hearing Research Center

The Cunningham Lab is interested in understanding the sensory and neural biology of the vertebrate auditory system, and in developing biological therapies for hearing loss. Many unique and highly specialized proteins with exquisitely precise subcellular localizations are critical for each step of sound processing. Hearing loss is the most common sensory deficit, and multiple forms of hearing loss involve aberrant assembly, trafficking, and/or regulation of key auditory proteins. We utilize mouse models of human deafness for our experiments. The similarities between the rodent and human auditory systems allow for a panoply of experimental manipulations that aim to uncover basic biological mechanisms and translational insights relevant for human health. The lab utilizes cutting-edge techniques including the generation and analysis of novel genetic mouse models combined with biochemistry, molecular biology, histology, viral vectors and high-resolution fluorescent microscopic imaging. Ultimately, we hope to utilize our findings toward the development of new therapies for hearing loss and deafness. To this end, we are very interested in developing gene therapy strategies that can treat hearing loss. Dr. Cunningham, along with Drs. Tzounopoulos and Zevallos from the Department of Otolaryngology-HNS, have recently co-founded a startup company called Echogenesis Therapeutics, focused on developing AAV-based gene therapies for individuals with genetic forms of hearing loss.

• Assistant Professor, Departments of Otolaryngology, Neurobiology, and Bioengineering

• Assistant Professor, Department of Otolaryngology

The McGovern Lab investigates the potential of the mammalian inner ear to regenerate following the loss of sensory cells that detect and transduce sound from the environment to the brain. These highly specialized cells are critical for our perception of the auditory world, but, unlike birds and fish, the mammalian inner ear has a very limited capacity to regenerate these cells and only early in development. The mature organ does not have any known capacity to naturally regenerate lost cells, and therefore our lab deploys transcription factors in order to reprogram lost sensory cells from their neighbors that remain in the ear.

We use genetically modified mouse lines that modify the transcriptome of cochlear cells specifically in mature non-sensory cells of the ear and investigate these through high resolution fluorescence histology and molecular genetic mechanisms. We are interested in understanding the circumstances necessary to reprogram non-hair cells into functional hair cells so that we can begin to design gene therapies for hearing restoration.

• Assistant Professor, Department of Otolaryngology-Head & Neck Surgery 

The primary challenge for systemic delivery to the inner ear is achieving a therapeutic dose across the blood-labyrinth barrier without causing systemic side effects. Local administration routes, such as intratympanic and intracochlear methods, present alternatives that bypass blood-labyrinth barrier issues encountered with systemic administration. However, these local methods come with drawbacks, including temporary or permanent hearing loss or low efficiency.

Our lab addresses the significant challenges inherent in developing effective inner ear substance delivery systems. One key hurdle involves not knowing the exact drug formulation for which the delivery system is being designed, affecting drug bioavailability and biodistribution. Another obstacle lies in translating promising findings from preclinical studies, conducted on animal models, into applicable solutions for human patients. Some of the current research projects to address these challenges are listed below:

1. Developing ex-vivo and in-vivo models of drug delivery in large animals such as pigs similar to humans.
2. Developing extracellular vesicles as efficacious and safe carriers to deliver therapy-related substances to the inner ear.
3. Identifying novel sensory receptors and channels of round window membrane that sense chemicals, investigating how receptors and channels regulate drug passage to the inner ear, and harnessing receptors and channels to improve inner ear drug delivery.
4. In vivo and ex-vivo 3D high-resolution imaging for inner ear visualization, metabolomics, inflammation, and drug biodistribution.
5. Evaluate promising regeneration therapy effects delivered safely in a clinically relevant animal model like pigs.
6. Nanomaterials and smart materials to improve drug delivery to the inner ear.

• Assistant Professor, Department of Communication Science and Disorders

The primary interest of the Parthasarathy Lab for Translational Auditory Neuroscience is in understanding how the peripheral auditory system and the central auditory pathway interact in various forms of hearing loss. The research program integrates study of human clinical populations and animal models, using non-invasive, EEG-like evoked potentials as the translational bridge. The overall goal is to inform diagnosis and track the benefits of interventional therapies in clinical populations with hearing loss by utilizing insights obtained from animal models with similar forms of pathology.

• Assistant Professor, Departments of Otolaryngology and Neurobiology

• Research Professor, Department of Otolaryngology-Head & Neck Surgery 

Dr. Xia has dedicated her career to hearing research, focusing on cochlear physiology and mechanics in various animal models, including mice, gerbils, and chickens. She has developed a transgenic mouse model, investigated gene regulation in the cochlea, and contributed to advancements in gene therapy for inner ear disorders.

Since 2017, Dr. Xia has collaborated with Dr. Peter Santa Maria as a co-investigator on an R01 grant, as well as on several SPARK programs, leading a group of researchers studying cochlear immunity mechanisms. Together, they investigate cochlear immune responses to sensorineural hearing loss caused by chronic suppurative otitis media, noise-induced hearing loss, and autoimmune or immune-mediated inner ear diseases. Dr. Xia is also an expert in topical drug delivery, drug kinetics, and drug ototoxicity screening.

• Research Assistant Professor, Department of Otolaryngology-Head & Neck Surgery

Vincent Yuan's translational research focuses on the mechanisms and treatment of chronic suppurative otitis media (CSOM) and Meniere's disease (MD), particularly from an immunological perspective, investigating both innate and adaptive immune responses. His studies examine how immune cells, such as macrophages and dendritic cells, are activated to produce proinflammatory mediators like TNFα and IL-1β. These cells not only drive inflammation but also influence the differentiation of T helper (Th) cell subsets, further escalating the immune response.

Additionally, Yuan's research explores the destructive effects, cell-cell crosstalk, and key signaling pathways activated by macrophages. A significant focus of his work is the role of the NLRP (NOD-like receptor protein) family in these processes. He investigates how NLRP proteins regulate inflammatory pathways that exacerbate chronic ear infections and inner ear disorders like MD. By exploring the interactions between innate and adaptive immune cells, Yuan aims to uncover critical mechanisms underlying unresolved inflammation in CSOM and MD, with the goal of identifying novel therapeutic targets.