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Research
UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
EMILY BUSS, PHD
CHIEF, DIVISION OF AUDITORY RESEARCH PROFESSOR
PAUL B. MANIS, PHD
CHIEF, DIVISION OF RESEARCH TRAINING AND EDUCATION PROFESSOR
MARGARET T. DILLON, AUD, PHD
DIRECTOR OF CLINICAL RESEARCH ASSOCIATE PROFESSOR
JOHN H. GROSE, PHD
PROFESSOR
DOUGLAS C. FITZPATRICK, PHD
ASSOCIATE PROFESSOR
LISA PARK, AUD
ASSISTANT PROFESSOR
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UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
RESEARCH
KENDALL A. HUTSON, PHD
ASSISTANT PROFESSOR
MEREDITH ANDERSON ROOTH, AUD
ASSISTANT PROFESSOR
MICHAEL KASTEN, PHD
ASSISTANT PROFESSOR
NATALIA ISAEVA, PHD
ASSISTANT PROFESSOR
MARGARET RICHTER, AUD
RESEARCH INSTRUCTOR
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FACULTY PUBLISHED PEER-REVIEWED PAPERS
RESEARCH
UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
The mission of the Department of Otolaryngology/Head & Neck Surgery (OHNS) is to improve the health of North Carolinians and others whom we serve. One of the objectives to fulfilling this mission is to carry out basic science, clinical, and health services research that advances the field of OHNS. Notable research accomplishments by clinical divisions within OHNS are included in those division reports. Below is an overview of the focus and accomplishments of the laboratories within OHNS that are directed by full-time research faculty.
RESEARCH HIGHLIGHTS
o Margaret Dillon successfully defended her PhD dissertation research on Place-based Mapping
With Electric-Acoustic Stimulation o John Grose received a new R01 to study Binaural Processing and Spatial Hearing: Effects of
Age and Hearing Loss o Participated in and continued to conduct 7 clinical trials assessing new indications for cochlear implantation in children and adults o Renewal of $700k industry grant (Over $3M since inception) o Added a new research audiologist, Dr. Gretta Richter, to our team o Trained 10 audiology students in cochlear implant clinical research o Drs. Park and Dillon chaired multi-institutional guidelines papers for the American Cochlear
Implant Alliance on single-sided deafness
THE HEAD AND NECK ONCOLOGY LAB
The Head and Neck Oncology Lab is guided by Wendell Yarbrough, MD, MMHC, FACS, and Natalia Isaeva, PhD. Research projects in the laboratory are funded by NIH NIDCR and focus on understanding the role of human papillomavirus (HPV) in the development, maintenance, and progression of head and neck squamous cell carcinoma (HNSCC). The discoveries are leveraged to identify and test novel therapeutic strategies that exploit susceptibilities of HPV-associated HNSCC, as well as to find prognostic molecular biomarkers that could be used to personalize treatment.
One big project, led by a postdoc Hina Rehmani, explores demethylation therapy as a potential treatment in HPV+ HNSCC using 5-azacytidine, an FDA approved agent that is utilized clinically to treat myelodysplastic syndromes and refractory cases of acute myelogenous leukemia. The results from this study resulted in 4 publications and were presented by Hina at national and international conferences.
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UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
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Another program in the laboratory examines an etiologically distinct subset of HPV+ HNSCC characterized by inactivating mutations or loss of TRAF3 or CYLD leading to constitutively active NF-kB. The first outcomes of this study, directed Travis Shrank, MD/PhD, and the graduate student Aditi Kothari, were presented at AACR meetings and in 2 publications. Dr. Schrank also received NIH NIDCR K08 award to investigate mechanisms NRF2, a crucial regulator of the cellular oxidative stress response, pathway activation head and neck cancer.
COCHLEAR IMPLANT CLINICAL RESEARCH LAB
Margaret ‘Meg’ Dillon, AuD, PhD directs the Cochlear Implant Clinical Research Lab, with research audiologists Lisa Park, AuD, Margaret ‘Gretta’ Richter, AuD, and Meredith Rooth, AuD. by
of
in
Their current research focuses on outcomes of cochlear implantation in children and adults with residual hearing and unilateral hearing loss, procedures for individualizing and optimizing mapping procedures, and effects of age at implantation on outcomes. The team also includes Michelle Bocanegra (Clinical Research Coordinator), Shannon Culbertson (Research Extern), and 5 graduate Research Assistants: Stephanie Panoncillo, Connor Zimmerman, Darla McDonald, Julie Doherty, and Jacqueline Eberhard. Many of the studies are collaborations with team members from the Divisions of Auditory Research, Neurotology/Otology & Lateral Skull Base Surgery, Pediatric Otolaryngology, Children’s Cochlear Implant Center, and audiologists from UNC Health who specialize in the treatment and management of adult cochlear implant patients.
The Cochlear Implant Clinical Research Lab is funded by the National Institute on Deafness and other Communication Disorders (NIDCD) and an industry grant from MED-EL Corporation.
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UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
Of the 21 peer-reviewed manuscripts this year, 12 were first authored by a trainee (Neurotology Fellow, UNC ENT Resident Physician, Doctorate of Audiology graduate student, or UNC medical student). Also, four trainees received awards for their research: o Shannon Culbertson: James & Susan Jerger Excellence in Student Research Award at the
American Academy of Audiology o Victoria Sweeney: James & Susan Jerger Excellence in Student Research Award at the
American Academy of Audiology o Erin Lopez, MD: First Place Triological Poster Award – Otology & Neurotology o Heidi Martini-Stoica, MD, PhD: Resident Presentation Award at the North Carolina/South
Carolina Societies of Otolaryngology – Head & Neck Surgery 2022 Assembly
Other noteworthy accomplishments from the Cochlear Implant Clinical Research Lab this year include the publication of two papers on guidelines for the clinical assessment and management for children and adults with single-sided deafness. Drs. Dillon and Park were invited by the American Cochlear Implant Alliance to lead task forces specific to adult and pediatric patients with single-sided deafness, respectively. These manuscripts were published this year by Ear & Hearing. Drs. Park and Dillon also disseminated this information as part of an AudiologyOnline continuing education series, and Dr. Dillon was a featured guest on the ENT in a Nutshell podcast on single-sided deafness.
HEARING RESEARCH LABS
The Psychophysics & Electrophysiology Auditory Research Laboratory (PEARL) is directed by John Grose, PhD. PEARL launched a new project funded by the NIH NIDCD in the past year that is focused on the hearing difficulties experienced by older listeners, both with and without hearing loss, in everyday settings where multiple sound sources are present at the same time. The purpose of this project is to obtain a comprehensive characterization of the spatial hearing abilities of adults across a wide age range, with a particular emphasis on differentiating effects of age and hearing loss. The findings will be directly relevant to the public health challenge of addressing the communication difficulties experienced by the burgeoning older population.
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As part of this new initiative, the PEARL team welcomed Monica Folkerts, PhD as a post-doctoral fellow. She joins the lab from Vanderbilt University where she completed her doctorate on spatial weighting cues under the direction of Chris Stecker, PhD. Another project in PEARL that is now reaching completion is a feasibility study on simultaneous measurement of the electricallyevoked compound action potential and Wave V of the auditory brainstem response in cochlear implant users. This project, headed up by neurotologist Matthew Dedmon, MD, was largely undertaken by PhD student Stacey Kane, AuD and AuD student Jenna Van Bosch.
The Speech Perception and Auditory Research at Carolina (SPARC) lab, directed by Emily Buss, PhD has been focusing on two main research themes this year. This first is a series of studies of auditory function in children with Auditory Neuropathy Synchrony Disorder (ANSD). This work is directed by Stacey Kane, AuD, and funded by an F32 grant from NIH NIDCD. ANSD is commonly characterized by disruption in the synchronous transmission of acoustic signals within the auditory system, resulting in deficits primarily in the temporal domain. The goal of this project is to better understand the functional consequences of ANSD for the ability to discriminate simple features of sound, for speech perception, and for development of spoken language. Results of these experiments will comprise Dr. Kane’s PhD dissertation. The second series of experiments in SPARC this year has focused on the measurement and functional utility of audibility above 8 kHz, referred to as the extended high frequency (EHF) range. This research is funded by a subaward of a grant from NIH NIDCD to Brian Monson, PhD at the University of Illinois. This research evaluates optimal procedures for testing EHF sensitivity in children and adults and employs computational modelling to explain the marked threshold differences that can be observed at these frequencies. Preliminary data were presented by Stacey Kane and AuD student Kathryn Sobon at the 2022 meeting of the American Auditory Society.
In addition to the personnel listed above, the hearing research labs run smoothly with help from AuD students Kaitlyn Thompson, Olivia Zimmerman, Selena Marcum, Chloe Gratzek, and Caroline Paroby.
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UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
Paul Manis, PhD directs the Cellular Mechanisms of Auditory Neural Information Processing lab. Michael Kasten, PhD and Kendall Hutson, PhD also conduct research in this lab. The team studies the cochlear nucleus and auditory cortex in animals, utilizing a range of electrophysiological and optogenetic stimulation techniques to determine the properties of defined cell types and damage associated with noise or age. Experiments investigate how sensory information about sound is processed in the brain – at a cellular and network level – using experimental approaches and computational models. They study auditory processing in both normal hearing and under conditions of defined hearing loss. Reginald Edwards, a 4th year graduate student in Cell Biology and Physiology, has joined the Manis Lab this year. Reggie is studying the organization of the axon initial segment in dorsal cochlear nucleus cells, and how that organization is modified by noise-induced hearing loss. The axon initial segment is the cell site where action potentials are initiated, and it has been shown to have activity-dependent structural changes which in turn affect the electrical excitability of the neurons. The neurons he is studying in the cochlear nucleus are thought to play a role in the generation of tinnitus through changes in their electrical excitability.
Dr. Ken Hutson shows the power and beauty of Light Sheet imaging with this image of the gerbil spiral ganglion and hair cells. Type I spiral ganglion cells (and their processes) are immunolabeled with TuJ1 (purple), while Type II spiral ganglion cells are immunolabeled with Peripherin (cyan). Spiral ganglion cells carry afferent information from hair cells (yellow) to the brain via the auditory nerve. Type I cells innervate the single row of inner hair cells, Type II cells innervate the three rows of outer hair cells.
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UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
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One notable achievement is the identification of a subset of spiral ganglion cells, thought to be involved in noise-induced and age-related hearing loss, which are specifically labeled in a mouse line that they have been working with for several years. Normal patterns of excitation of these cells have been mapped onto the principal neurons in the auditory brainstem. Current blinded experiments are investigating how these cells, which are thought to be more sensitive to noise-induced hearing loss than other sets of spiral ganglion cells, interact with central auditory neurons following noise-induced hearing loss. The identification of the cells by a combination of fluorescence methods in surface preparations and light-sheet imaging was done initially by lab members Tessa Ropp, PhD, and subsequently refined by Ken Hutson, PhD. Another notable achievement is the use of a combination of serial-blockface electron microscopy and computational modeling to characterize the auditory nerve inputs and patterns of connectivity onto one major cell type, the bushy cell. These patterns affect how the central auditory neurons integrate information from the cochlea and achieve better timing precision than present in the cochlea. Such timing is needed for understanding speech and for identifying the location of sounds around us. This line of work also identified new anatomical structures associated with the central auditory neurons. These studies are at the forefront of “connectomics”, the study of detailed and precise connectivity between neurons in the brain. This work is part of a collaborative project between Drs. Paul Manis (UNC), George Spirou (University of South Florida) and Mark Ellisman (University of California at San Diego).
The Manis Lab is funded by the National Institute on Deafness and other Communication Disorders (NIDCD) and National Institute of Neurological Disorders and Stroke (NINDS).
AUDITORY PHYSIOLOGY LAB
Douglas Fitzpatrick, PhD directs the Auditory Physiology Lab, using both animal and human models in studies to understand the neural basis of auditory processing and associated changes due to hearing loss. Kendall Hutson, PhD works in the Auditory Physiology Lab, contributing expertise in imaging and neuroanatomy including light sheet microscopy of the mammalian cochlea, a method that generates 3D images of spiral ganglion cells, hair cells, and stria vascularis. Currently, the team also includes two undergraduate research assistants, Greta LeitzNajarian and Alex Dunn.
The Auditory Physiology Lab maintains collaborations with many clinicians and researchers in UNC ENT as well as with The Ohio State University, Washington University in St. Louis, and North Carolina State University. These collaborations cover a range of topics, from animal
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UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
anatomy and physiology to factors predicting cochlear implant outcomes in humans, to potential new technologies for improved hearing loss therapies.
CLINICAL RESEARCH
The OHNS Clinical Research Accountability Unit (CRAU) was established this year. The role of the OHNS CRAU is to 1) disseminate information and resources from the UNC School of Medicine, its Clinical Research Support Office (CRSO), and the Offices of the Vice Chancellor of Research (OVCR) to research teams in our department, 2) develop methods to verify the accuracy of administrative data to appropriately understand and account for all studies and personnel involved in human subjects research, and 3) disseminate and promote established best practices and standard operating procedures to bolster efficiency.
CRAU Faculty Director:
o Wendell Yarbrough, MD, MMHC, FACS, Chair of OHNS
CRAU Co-Administrative Directors:
o Emily Buss, PhD, Vice Chair of Research o Meg Dillon, AuD, PhD, Director of Clinical Research Dr. Doug Fitzpatrick’s recent publication shows the different components that contribute to the summating potential.
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UNC Department of Otolaryngology ⁄ Head and Neck Surgery 21-22 Annual Report
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