Workplace Notes From the Field

Notes From the Field and Clinic

Physician-scientists bring multiple perspectives to treating patients and conducting research.

By Ronna Hertzano, M.D., Ph.D.

Training in the gEAR—a tool that provides intuitive visualization, analysis, and sharing of gene expression data—occurred at the last in-person Association for Research in Otolaryngology MidWinter Meeting, in early 2020. I am an otolaryngologist surgeon-scientist. My clinical practice focuses on the diagnosis and treatment of diseases of the ear, with an emphasis on hearing restoration. As such, I see and treat patients of all ages who suffer from hereditary and nonhereditary auditory (hearing) and vestibular (balance) dysfunction. Over 60 percent of my time is dedicated to research, where my goal is to make significant contributions toward the treatment of congenital and acquired auditory and vestibular dysfunction. Toward hearing restoration, I work to unravel the regulatory signaling cascades that lead to the proper development of the ear, specifically sensory hair cells in the inner ear. I lead a collaborative team that develops and applies a variety of approaches for cell type-specific, multi-omic analyses of the ear. We couple the results of these studies with state-ofthe-art informatics analyses to identify key regulators of gene expression in hair cell development, and cell type-specific signaling cascades in acquired hearing loss (e.g., from excess noise or aging).

Several years ago, I realized that the lack of intuitive tools for the noninformatics–trained biologists for visualization and analysis of omics data presents a major barrier to the effective dissemination, sharing, and analysis of expression data by cellular and molecular biologists.

This led to the inception and development of the gEAR (gene Expression for Analysis Resource), a tool that provides intuitive visualization, analysis, and sharing of gene expression data. Hearing Health Foundation (HHF)’s Hearing Restoration Project helped provide seed funding for the platform.

The gEAR portal allows anybody in the scientific community who is studying noise-induced hearing loss seamless access to our dataset without having to download the data and format it. They can also analyze the data using the gEAR.

Two Ways of Thinking

I believe all physician-scientists (also called clinician-researchers) share the dream of helping to advance how we treat human diseases. We also share the path—which includes active listening to patients, creative thinking, lab meeting discussions, forming collaborations, and staying at the forefront of research. Ideally we’ll be able to develop experiments in model organisms followed up by clinical studies among the patient population.

Only 40 to 50 percent of people with congenital hearing loss have an identifiable mutation. At my institution, the University of Maryland School of Medicine, we have a protocol where we are able to draw blood from patients and, for research, have it genetically tested. This research is in collaboration with two of my basic science genetics colleagues. As a result, we can perform exome sequencing on patients with hearing loss, and this will allow us to potentially identify new deafness genes.

I believe that having a research background allows me to listen to patient concerns differently and constantly ask myself mechanistic research questions. Often the issues overlap or coincide, and by looking at things from the physician’s and scientist’s perspectives I’m able to gain context for the variety of ear diseases in my patients. For example, we are studying sex differences in hearing and susceptibility to noise-induced hearing loss. This has made us interested in the estrogen signaling pathway in hearing.

The Latest Findings

Another important aspect of being a physician-scientist is the ability to critically review the literature and follow the most recent findings reported at conferences. This helps me identify opportunities for patients who may benefit from clinical trials.

For example, at a recent Association for Research in Otolaryngology MidWinter Meeting, which is the top research conference for hearing and balance scientists, I saw a presentation by Lisa Cunningham, Ph.D., of the National Institute on Deafness and Other Communication Disorders, about a possible treatment to prevent hearing loss as a side effect in head and neck cancer patients treated with the common chemotherapy drug cisplatin.

Because I was at the meeting, and also a hearing restoration surgeonscientist interested in offering opportunities to our patients, I was able to reach out to the presenter as well as head and neck doctors and oncologists at my institution. We are working on facilitating a collaboration that will hopefully lead to being able to include our patients as part of a prospective clinical study.

The dual approach of being a physician-scientist makes for a very fulfilling experience and leads to advancements in patient care as a field. It allows us to answer patient questions in a thoughtful and educated manner because of a very broad exposure to data, and experiencing firsthand the patient’s concerns brings a human dimension to our research.

A 2009–2010 Emerging Research Grants (ERG) scientist and a member of HHF’s Hearing Restoration Project (HRP), Ronna Hertzano, M.D., Ph.D., is a professor in the department of otorhinolaryngology–head & neck surgery at the University of Maryland School of Medicine. For more about the gEAR, see page 41. Hertzano and HRP scientific director Lisa Goodrich, Ph.D., presented the HRP’s research as part HHF’s Hearing Health Hour webinar series. View captioned recordings at hhf.org/webinar. I believe all physician-scientists (also called clinicianresearchers) share the dream of helping to advance how we treat human diseases. We also share the path—which includes active listening to patients, creative thinking, lab meeting discussions, forming collaborations, and staying at the forefront of research. Ideally we’ll be able to develop experiments in model organisms followed up by clinical studies among the patient population.

A Direct Impact on Quality of Life

The Central Sensory Processes Laboratory at University of Texas at Austin investigates the causes of central auditory deficits.

By Julia Campbell, Au.D., Ph.D., CCC-A, FAAA

It’s not about the grants or the papers. It’s about learning how to help people and improve their quality of life through the right kinds of scientific questions, leading to scientific breakthroughs.

My favorite thing to tell my students is that the best research questions come from the clinic.

This is where we can have a direct impact on others’ quality of life. For instance, at a recent conference I asked attending clinicians whether they had been seeing an increase in patients with typical hearing but concurrent auditory disorders. Every single person raised their hand to indicate that, indeed, they were testing patients who scored within the “normal” range on typical clinical measures but who still reported significant auditory dysfunction, such as tinnitus (ringing in the ears), misophonia (adverse emotional reactions to certain sounds), and difficulty understanding speech in the presence of background noise.

I have also personally interacted with patients who fall into the previous categories. One such individual was suffering from severe tinnitus but was told by a physician, “There’s nothing we can do.” Not only are the usual diagnostic measures insensitive to the reported auditory dysfunction, but there are few to no effective interventions available for these populations. Seeing the frustration of patients and clinicians alike has motivated our lab, the Central Sensory Processes Laboratory at the University of Texas at Austin, to investigate the underlying causes of central auditory deficits that occur despite the indication of “normal” hearing. Once these causes are better understood, we can progress to effective treatments that target the site of dysfunction, alleviating the symptom.

My father had a repeat cholesteatoma (a cyst in the ear), and a viral infection of the vestibular nerve, so he has a middle ear prosthetic as an ossicle replacement. I provided insights into the science while he shared the personal aspect of what patients go through. Speaking with individuals suffering from tinnitus and/or hearing loss, as well as those with various neurological disorders, reminds one of the importance of research.

It’s not about the grants or the papers. It’s about learning how to help people and improve their quality of life through the right kinds of scientific questions, leading to scientific breakthroughs. By listening to our patients and clinicians, we will be able to better help underserved populations that may otherwise experience something akin to indifference by the medical community.

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A 2016 ERG scientist generously funded by the Les Paul Foundation, Julia Campbell, Au.D., Ph.D, CCC-A, FAAA, is an assistant professor in the department of speech, language, and hearing sciences at the University of Texas at Austin, where she is also the director of the Central Sensory Processes Laboratory.

Role Models for the Research

By Bryan K. Ward, M.D.

I was the first in my family to graduate from a fouryear college and was inspired to enter medicine by our pediatrician. He was a comfort to all of us and a great role model of a family physician, helping my sister who had multiple serious health issues during my childhood. At birth she experienced an intraventricular hemorrhage and from a young age had bilateral sensorineural hearing loss.

Since receiving HHF funding, I have taken a great interest in Ménière’s disease (a hearing and balance disorder) and several projects have emerged from this grant. Some are real discoveries in the pathophysiology of Ménière’s disease, which is exciting. I learned from watching my sister struggle with imbalance and falls that balance is just as important as hearing and often significantly underappreciated.

Being a clinician provides motivation for the research. Every week in my clinic I see patients with Ménière’s disease and other disorders of the inner ear vestibular system that are not well understood. I have also discovered that patients with Ménière’s disease are excited to participate in research. They understand that despite our knowing about this condition for over 150 years, we have few answers for them, and they want to help us find answers.

Bryan K. Ward, M.D. (center) with colleagues Jacob Pogson, Ph.D. (left), and Dale Roberts.

A 2020 ERG scientist, Bryan K. Ward, M.D., is an assistant professor of otolaryngology–head and neck surgery at Johns Hopkins University School of Medicine.

Hearing and the Brain By Samira Anderson, Au.D., Ph.D.

As a clinical audiologist for 26 years, I enjoyed helping people improve the quality of their lives through better hearing with the use of hearing aids. At the same time, I also felt frustrated when my patients continued to have trouble hearing in challenging listening situations, such as in noisy backgrounds, even with hearing aids with advanced technology.

What has been especially puzzling is that two people with identical hearing tests may report quite different listening experiences in the same environments while wearing the same hearing aid technology. These observations led me to question what happens to speech after it has been processed by hearing aids, and whether the brain’s processing of speech is degraded in some individuals, especially as they age.

For these reasons, I left my clinical practice in Minnesota to pursue a Ph.D. at Northwestern University in Illinois. I worked toward my doctorate at Northwestern’s Auditory Neuroscience Laboratory (now called Brainvolts), which is overseen by Nina Kraus, Ph.D. While there, my focus was on examining how the brain processes sound in individuals who have difficulty understanding speech in noise, such as older adults or people who have hearing loss.

This is research that I continue today, examining how hearing loss alters the way our brains respond to speech and how it may affect cognitive functions, such as working memory, and how hearing aid amplification can reverse these changes.

A 2014 ERG scientist generously funded by the General Grand Chapter Royal Arch Masons International, Samira Anderson, Au.D., Ph.D., is an associate professor in the department of hearing and speech sciences at the University of Maryland, where she also oversees the Hearing Brain Lab. She presented her research as part HHF’s Hearing Health Hour webinar series, at hhf.org/webinar.