The labs within the Department of Otolaryngology - Head & Neck Surgery at Northwestern University Feinberg School of Medicine conduct regular research to build on our understanding of our subspecialties and the conditions we treat. Learn more about the work being done in our individual labs via the links below.
Auditory Research Laboratory
Areas of Research
Development of cochlear implants including novel devices based on neural infrared stimulation, use of laser in clinical settings, micromechanics of the cochlea, imaging, medical device development.
The interest of my group is to characterize the function of the normal inner ear, to compare it to the function of a damaged ear, and to develop means and strategies to alleviate hearing impairment. Cutting edge studies include: experiments on cochlear micromechanics, cochlear soft tissue imaging with hard X-rays, research on redesigning cochlear implant devices which use light for neural stimulation, and the development and testing of novel laser sources. In particular, the lab’s recent work on the development of laser based cochlear implants has attracted the interest of many researchers, engineers, and practitioners. Our lab was the first to explore optical radiation as a means of stimulating auditory neurons as an alternative to electrical stimulation, using and studying this novel approach since 2004. In NIH and DoD funded projects, we have determined basic laser parameters that allow us to safely stimulate auditory neurons over several hours. Together with an industrial partner, laser units that are chronically implantable in a cat animal model were developed and tested. Behavioral results from implanted cats demonstrate that the animals receive an auditory input. Our goal is to further the technology towards a human device.
Auditory Molecular & Cell Biology Laboratory
Areas of Research
Cell biology, hearing sciences, molecular neuroscience
The goal of my lab is to identify and investigate molecules that play important roles in mammalian hearing, balance, and olfaction. Our research has been centered on several important proteins and their associated diseases.
Molecular Basis for Ciliopathies
Defective ciliary function results in otitis media, hearing loss, anosmia, rhinitis, sinusitis, and other symptoms that are collectively referred to as ciliopathies. We have identified CAMSAP3 as one of the components required for ciliogenesis. We are investigating the functions of CAMSAP3 in both motile ciliated cells and non-motile sensory cells, which include olfactory sensory neurons. As cilia defects have significant implications for human health, a more thorough understanding of CAMSAP3’s contribution to the proper assembly and function of cilia will help to develop better treatments for various diseases.
Molecular Basis of Cochlear Amplification
Outer hair cells (OHCs) undergo rapid somatic length changes when the voltage across their membrane is altered. This unique somatic electromotility provides the local mechanical amplification of the cochlear response to sound. Without OHCs, the hearing threshold is elevated by 40-50 dB and frequency resolution deteriorates. Prestin is the motor protein of OHCs and it is required for cochlear amplification (Zheng et al., Nature, 2000). Coincidently, prestin is only expressed in OHCs, which are also the most vulnerable cells in the organ of Corti. We are investigating the connection between prestin’s function and the vulnerability of OHCs to a variety of ototoxic exposures including noise exposure. These studies will not only expand knowledge of prestin as the OHC-based cochlear amplifier at the molecular level, but also produce a deeper understanding of mechanisms associated with outer hair cells loss and synaptopathy.
Cochlear Drug Discovery Laboratory
Areas of Research
Drug Discovery for Hearing Loss; Noise Induced Hearing Loss; Nerve Fiber Regeneration; Mechanisms of Neurite Growth
The Whitlon Lab is actively engaged in research aimed at developing drugs for hearing loss by examining cochlear nerve fiber regeneration in culture models, by examining promising drugs in animal models of noise induced hearing loss, and by elevating promising drugs to clinical trial.
Our group studies ways to prevent or repair hearing loss, which is a significant medical problem. According to the National Institute for Deafness and Other Communicative Disorders (NIDCD), approximately 17% of American adults report some degree of hearing loss. In the group that are 75 years of age and older, more than 45% have a hearing loss. However, at present, there are no drugs that are FDA approved to treat this problem. As hearing loss can interfere with communication, socialization, work efficiency, and other aspects of health, it is critical that interventions be developed to prevent or repair hearing loss.
In a novel cell culture system using newborn mouse cochlear neurons, we found that some members of the statin class of drugs stimulate regeneration of damaged cochlear nerve fibers. We elevated one member of that family, fluvastatin, to evaluation in a guinea pig model of noise induced hearing loss and found that it also protects against hearing loss as well as protects the sensory cells, the hair cells, from degeneration. We have found a similar result in mice, and also showed that the drug protects the synapses between the hair cells and the cochlear neurons. We continue to examine compound libraries for their effects on regeneration of nerve fibers in vitro, and hearing loss in vivo, and are delving into the mechanisms by which they work. These studies have set the stage for a clinical trial of statins and hearing loss to begin in 2021.
Pediatric Airway Research Laboratory
Areas of Research
My research focuses primarily on conditions that lead to airway obstruction in children as well as the feeding and swallowing disorders that can accompany these conditions and their treatments. I also am interested in pediatric obstructive sleep apnea and its causes, diagnosis and treatments.
I perform primarily clinical research that focuses on conditions that lead to airway obstruction in children as well as the feeding and swallowing disorders that can accompany these conditions and their treatments. I am also collaborating with the division of Sleep Medicine at CMH on several retrospective and prospective sleep apnea studies. My translational research interests include studying the role of salivary amylase and pepsin found in the bronchial secretions in children with and without tracheotomy. I am working with the Departments of Otolaryngology and Allergy and Immunology at Feinberg looking at inflammatory mediators in children with chronic sinusitis and nasal polyposis as part of a larger adult study funded by an NIH grant.
Northwestern University Sinus & Allergy Center
Areas of Research
Immunopathogenesis of chronic sinusitis, biomarkers for determining outcome in chronic sinusitis, evidence-based medicine, clinical outcomes, clinical trials.
I am a clinician-scientist whose research interests are to understand the molecular and immunopathologic changes found in chronic rhinosinusitis (CRS) and their impact on clinical outcomes. The ultimate long term goal of my work is to find novel means to treat patients with this disease. CRS is a chronic and debilitating inflammatory condition of the nose and paranasal sinuses that affects millions of adults. Since there is little known about the pathobiology of this common disease, my research, in conjunction with the Northwestern University Sinus and Allergy Center, takes a multi-pronged approach.
Understanding B-cell and antibody responses in CRS
In the subtype of CRS associated with nasal polyp formation (CRSwNP), there is extensive activation of B-cells and their consequent antibody responses. This is driven by molecular factors including the over-expression of related chemokines and cytokines such as BAFF (Kato et al., JACI 2008). Evidence for dysregulation of their antibody responses can be found in the production of locally and in some instances systemically elevated levels of self-reactive autoantibodies (Tan et al, JACI 2011; Jeffe et al, Laryngoscope 2013; van Roey et al, JACI 2017; Min et al, JACI 2017). Our NIH funded research focuses on understanding the specificities of these autoantibodies, the clinical implications of self-reactive antibodies in the nose, airway and circulation and studying their potential to serve as biomarkers for more aggressive, treatment resistant varieties of CRS.
Understanding the molecular mechanisms of Type 2 inflammation
CRS is among the most common causes of reversible smell loss in patients but yet about half the patients do not reliably regain their sense of smell following treatment. The mechanism by which this smell loss occurs is yet unknown but appears to be a combination of conductive effects and direct damage to the olfactory region. We have found that Type 2 inflammation characterized by eosinophils, and the cytokines IL-5 and IL-13 are the strongest predictors of smell loss in patients with CRS (Thompson et al, IFAR 2016; Lavin et al, Laryngoscope 2017; Min et al, JACI 2017). Our NIH funded laboratory focuses on understanding the mechanisms by which Type 2 inflammation causes epithelial and olfactory neuroepithelial damage and pharmacologic strategies to reverse these changes.