About the Researcher

Litao Tao, PhD, is an assistant professor in the Department of Biomedical Sciences within the School of Medicine at Creighton University. He received his PhD and post-doctoral training in University of Southern California under the supervision of the late Dr. Neil Segil. The team led by Dr. Tao is focusing on functional genomics of the inner ear, hoping to reveal the epigenetic mechanisms governing cell fate specification and to identify key regulatory elements for hair cell preservation and regeneration.

About the Research

High-throughput and quantitative measurement of hair cell distal enhancers

The sound detection function of sensory hair cells depends on strict regulation of gene expression, which is largely controlled by promoters – DNA sequences immediately upstream of genes. Also within our genome are regions called enhancers, which interact with promoters to regulate gene expression. Approximately half of hereditary deafness patients do not have mutations within gene bodies or promoters, so we suspect these cases are due to mutations in enhancers. However, enhancers are difficult to identify because they are far away from their target genes. This, coupled with the challenges of working with delicate hair cells, has left us with little understanding of the role enhancers play in gene regulation to ensure the proper function of hair cells, impeding accurate diagnosis of many hereditary hearing loss patients. Our research implements a new strategy to overcome these obstacles to identify enhancers regulating hair cell genes.

About the Researchers

Keiko Hirose is a pediatric otolaryngologist and physician-scientist with expertise in caring for children with hearing loss and chronic ear disease. Her research program explores innate immunity of the inner ear and infectious conditions that affect hearing such as pneumococcal meningitis and congenital CMV. The Hirose lab has demonstrated how inflammation affects normal cochlear physiology and the blood perilymph barrier. This project on cholesteatoma provides a new opportunity to study resident macrophages and inflammation in the middle ear and to understand their contribution to cholesteatoma recurrence and outcome.

Daniel Romano is a postdoctoral scholar and otolaryngology resident at Washington University, supported by the NIDCD R25 grant. He graduated from Purdue University with a degree in Biomedical Engineering and Indiana University where he received his MD. The concept for this project on pediatric cholesteatoma originated on his rotation at St. Louis Children’s Hospital while discussing recurrence rates and destructive potential of cholesteatomas and our limited tools to cure this disease.  Dr. Romano brings expertise in scRNA-seq and bioinformatics in addition to creativity and novel perspectives on transforming the care of patients with cholesteatomas.

About the Research

Revealing molecular and cellular drivers of cholesteatoma pathogenesis and recurrence in children using single-cell RNA sequencing

Cholesteatomas are cystic masses that are associated with chronic ear infections and cause damage to structures needed for hearing. Children are prone to developing cholesteatomas and often require repeated operations to control disease.  We will perform experiments to improve our understanding of the causes of cholesteatoma and how to stop their growth.  We will use a technique called single-cell RNA sequencing to explore which genes are expressed in individual dispersed cholesteatoma cells from surgical specimens. Spatial transcriptomics will be used to study gene expression of cholesteatoma in tissue sections, to demonstrate where the cells are located that express abnormal genes within the cholesteatomas. Using these two techniques, we hope to achieve a better understanding of what steps lead to cholesteatoma and what we can do to stop their growth and eliminate them more effectively.

About the Researcher

Joaquin Cury, PhD, is a postdoctoral researcher in the Department of Otolaryngology at Northwestern University in Chicago, Illinois. He completed his bachelor’s degree in bioengineering in Argentina; and his Master’s degree in management and development of biomedical technologies in Madrid, Spain. Dr. Cury received his PhD in engineering sciences and technology at Université libre de Bruxelles, Belgium. Dr. Cury’s research is centered on the exploration and application of emerging optical technologies in the field of next-generation implantable medical devices. Currently, he is working in the design and development of infrared laser-based cochlear implants.

Claus-Peter Richter, MD PhD, is a Professor in the Department of Otolaryngology at Northwestern University in Chicago, Illinois. He is Vice Chair of Research and holds joint appointments in the Departments of Biomedical Engineering; and Communication Sciences and Disorders. He is a Fellow of the Hugh Knowles Center for Clinical and Basic Science in Hearing and Its Disorders. His research interests relate to the improvement of cochlear implants, the micromechanics of the mammalian cochlea, and the maturation of the mammalian inner ear. Recently, the research efforts of his laboratory are focused on developing cochlear implants that use optical radiation to stimulate auditory neurons.

Xiaodong Tan, PhD, is an Assistant Professor in the Department of Otolaryngology at Northwestern University in Chicago, Illinois. Dr. Tan earned his PhD degree at Creighton University and received his postdoctoral training at University of Wisconsin-Madison and Northwestern University. Dr. Tan’s studies contributed to the structural and functional evolution of prestin and the application of infrared neural stimulation in the cochlear implants. Currently, his research interest is hearing protection against cisplatin ototoxicity, as well as against other insults including drug, noise, and age.

About the Research

Design, Development, and Implementation of an Optical System to Preserve Residual Hearing and Evaluate Cochlear Health in Patients Receiving a Cochlear Implant

Globally, hearing loss affects over 1.5 billion people, with around 30 million severely-to-profoundly deaf individuals being candidates for cochlear implants (CIs). Recognized as one of the most successful neural prosthetics, CIs nevertheless pose surgical risks, including the potential for inner ear damage which results in residual hearing loss in at least 32% of implantations, thereby diminishing the overall benefits of CIs.

While progress has been made in designing smaller, more flexible CI electrodes and improving monitoring methods for insertion, current techniques predominantly detect cochlear damage only after it has occurred, often operating ‘blindly’ during crucial insertion stages of the electrode. Recent advancements in nano camera technology offer a promising solution. Miniaturized cameras have the potential to provide real-time visualization of the cochlea conduit during the electrode insertion, revolutionizing the procedure.

About the Researcher

Samuel Mathias received his PhD in Experimental Psychology at the University of York, UK, and worked as a postdoc at the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig, Germany, Boston University, and Yale University. He is currently junior faculty at the rank of Instructor at Boston Children’s Hospital and Harvard Medical School. He has published on a variety of topics, ranging from basic auditory perception to the genetic basis of complex traits and diseases. He was recently awarded an R01 from the National Institute on Aging to explore the potential common etiologies of hearing loss and dementia.

About the Research

Early Warning Signs of Age-Related Sensorineural Hearing Loss

Age-related sensorineural hearing loss (ARSHL) is essentially impossible to prevent given current knowledge. It is not clear who will develop ARSHL before its primary symptoms emerge, and as these symptoms are caused by cell death, we are unable to reverse them. Therefore, accurate prediction and estimation of individual risk prior to primary symptom onset could greatly expand prevention and management options for ARSHL.

This study will search for antecedents or “early warning signs” of ARSHL. Fifteen normal-hearing people with at least one parent with ARSHL (the high-risk group) and 15 normal-hearing people without a parent with ARSHL (the low-risk group) will provide blood samples and undergo a battery of audiologic, psychoacoustic, self-report, and electrophysiologic assessments. We will test for group differences in these measures to establish them as early warning signs of ARSHL. We will also test for enrichment of rare genetic variation in deafness genes in high-risk individuals.

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About the Researcher

Dr. Akihiro J. Matsuoka, a double-board-certified neurotologist and otolaryngologist at UC San Diego Health, specializes in treating ear-related neurological disorders including vertigo, tinnitus, and hearing impairment. He is an associate professor at UC San Diego School of Medicine, focusing on balance and vestibular research, and has contributed significantly to the field with over 50 publications. Dr. Matsuoka’s prior roles include director of audiology at Northwestern Medicine and extensive research and clinical training at Indiana University, University of Iowa, and University of California San Diego. He is an esteemed member of several otolaryngology and stem cell research societies.

About the Research

Regenerating the Blood-Labyrinthine Barrier: Harnessing Induced Pluripotent Stem Cells for Ménière’s Disease Treatment

Our team at UC San Diego is pioneering a groundbreaking approach to combat Ménière’s disease, a debilitating inner ear condition. Utilizing the versatility of human induced pluripotent stem cells (hiPSCs), we aim to recreate and study the Blood-Labyrinthine Barrier (BLB) in the lab. This barrier is crucial for inner ear health and is central to the disease’s pathology. By guiding hiPSCs to become Microvascular Endothelial Cells, we can closely simulate the BLB, allowing for an in-depth exploration of its functions and dysfunctions. This research has the potential to shift the current treatment paradigm from merely symptom management to targeting the root cause of the disease. Our innovative approach not only holds promise for transforming Ménière’s disease treatment but also offers insights into other inner ear disorders, potentially leading to significant advancements in the field.

About the Researcher

Pei-Ciao Tang is a research assistant professor in the Department of Otolaryngology-Head and Neck Surgery at the University of Miami Miller School of Medicine. Her research focuses on understanding the molecular mechanisms underlying inner ear diseases, the development of the inner ear, and hair cell regeneration using the human stem cell-based system, with an overarching goal of developing therapeutic strategies for inner ear diseases, namely hearing loss.

About the Research

Development of an ‘organoid-on-a-chip’ platform for the study of dorso-ventral patterning in a stem cell model of the human inner ear

Hearing loss is amongst the most common sensory disorders. To study its causes, as well as develop treatments, it would be beneficial to have a human cell-based model. However, it is difficult to obtain inner ear tissues from humans. Thankfully, human pluripotent stem cells (hPSCs) have demonstrated the potential to serve as an alternative model for the study of human biology. The cochlea, which is responsible for hearing, emerges from the ventral side of the inner ear while the vestibular organs involved in balance sensing develop along the dorsal side. In this project, we will mimic signaling gradients during human development to drive dorso-ventral patterning in hPSC-derived 3D inner ear organoids within a microfluidic chip. The results will provide invaluable information of how best to culture hPSC-derived cochlear organoids, which will serve as a powerful tool for the 1) study of hearing loss and 2) testing of potential therapeutic approaches.

About the Researcher

Dr. Veeranna is an Assistant Professor in Audiology at the School of Speech and Hearing Sciences, University of Southern Mississippi. He received his Ph.D. in Hearing Science from the Health and Rehabilitation Sciences program at Western University, Canada. Dr. Veeranna’s research interest is in understanding auditory processing in individuals with and without listening difficulties (children and adults) using psychoacoustic and electrophysiological measurements.

About the Research

Auditory System Integrity in University Marching Band Students

Students enroll in marching band during high school (~12-13 years of age) years and a significant portion of these students may continue to participate in marching band till they
complete their undergraduate degree (~22-23 years of age). Marching band participants are exposed to hazardous noise levels for a longer duration (~ 10 years) indicating that these students are at risk of noise-induced hearing loss. It is well established in the literature that prolonged exposure to hazardous noise levels can cause permanent damage to the cochlea and auditory nerve synapses. However, currently, there is a scarcity of systematic investigation of auditory system function in students who are enrolled in the marching band. Hence, the goal of this project is to examine auditory system function in students who are enrolled in the university marching band. The auditory system function will be examined using clinical and advanced measures of auditory processing. The findings of this study will help in implementing a hearing conservation program for students enrolled in the marching band.