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Research and Clinical Trials
The experts in the Department of Otolaryngology-Head and Neck Surgery have dedicated themselves to advancing their field through thoughtful and groundbreaking research. Each of our eight research groups works diligently to constantly learn more about their topic and educated the medical community about their findings.
The following clinical trials are currently being offered by the Department of Otolaryngology-Head and Neck Surgery.
Has hearing research gone batty?
Hearing researcher Amanda Lauer – whose work is supported through the David M. Rubenstein Hearing Center – explains how she uses electron microscopy to examine synaptic and nanoscale structures. She collaborates with the Comparative Neural Systems and Behavior Laboratory, aka the Bat Lab, run by Krieger's Cynthia Moss, because bats are hearing specialists, using echolocation to survive.
The Agrawal Lab is focused on the medical and surgical treatment of otologic and neurotologic conditions. Research is focused on the vestibular system (the inner ear balance system), and how the function of the vestibular system changes with aging. Particular focus is given to study how age-related changes in vestibular function influence mobility disability and fall risk in older individuals.
Atul Bedi Lab
The Atul Bedi Lab in the Head and Neck cancer research program provides fundamental insights into the molecular determinants and mechanisms by which tumor cells evade death signals entrained by the immune system and anticancer agents. Their recent studies show that tumor-induced immune tolerance limits the in vivo anti-tumor efficacy of tumor-targeted antibodies and that the tumor cell-autonomous expression of transforming growth factor-b (TGF-b) is a key molecular determinant of the de novo or acquired resistance of cancers to EGFR-targeted antibody. Their laboratory has developed novel bi-functional antibody-based strategies to simultaneously counteract immune tolerance in the tumor microenvironment and to enhance the anti-tumor efficacy of targeted antibody therapies for the treatment of cancer.
The overall goal of the Auditory Brainstem Library is to understand how abnormal auditory input from the ear affects the brainstem, and how the brain in turn affects activity in the ear through efferent feedback loops. Our emphasis is on understanding the effects of different forms of acquired hearing loss (genetic, conductive, noise-induced, age-related, traumatic brain injury-related) and environmental noise. We are particularly interested in plastic changes in the brain that compensate for some aspects of altered auditory input, and how those changes relate to central auditory processing deficits, tinnitus, and hyperacusis. Understanding these changes will help refine therapeutic strategies and identify new targets for treatment. We collaborate with other labs in the Depts. of Otolaryngology, Neuroscience, Neuropathology, the Wilmer Eye Institute, and the Applied Physics Laboratory at Johns Hopkins, in addition to labs outside the university to increase the impact and clinical relevance of our research.
The Cochlear Neurotransmission Group studies the generation and propagation of neural signals in the inner ear. Our laboratories use biophysical, electrophysiological, molecular biological and histological methods to determine fundamental molecular mechanisms by which neurotransmitters are released from primary sensory cells ('hair cells') to excite second order neurons carrying information to the brain. We apply these same techniques to study inhibitory feedback produced by brain neurons that project to and regulate the sensitivity of the cochlea.
Daria Gaykalova Lab
The Daria Gakalova Lab defines the functional role of epigenetics in transcriptional regulation of head and neck squamous cell carcinoma (HNSCC) progression. To evaluate the whole-genome distribution of various histone marks, her team is using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-Seq) for primary tissues, a method recently developed by her lab. The research group of Daria Gaykalova was the first to demonstrate the cancer-specific distribution of H3K4me3 and H3K27ac marks and their role in cancer-related gene expression in HNSCC. The research showed that an aberrant chromatin alteration is a central event in carcinogenesis and that the therapeutic control of chromatin structure can prevent the primary of secondary cancerization. Further preliminary data suggest that the differential enrichment of these disease-specific histone marks and DNA methylation correlate with alternative splicing events (ASE) formation. For this project, Dr. Gaykalova and her team employed a novel bioinformatical tool for the detection of cancer-specific ASEs. Through thorough functional validation of the individual ASEs, the lab demonstrated that each of them has a unique mechanism of malignant transformation of the cells. Due to high disease specificity, ASEs represent the perfect biomarkers of the neoantigens and have direct application to clinical practice.
Research in the Glowatzki Lab focuses on the auditory system, with a particular focus on synaptic transmission in the inner ear.
Our lab is using dendritic patch clamp recordings to examine mechanisms of synaptic transmission at this first, critical synapse in the auditory pathway. With this technique, we can diagnose the molecular mechanisms of transmitter release at uniquely high resolution (this is the sole input to each afferent neuron), and relate them directly to the rich knowledge base of auditory signaling by single afferent neurons.
We study pre- and post-synaptic mechanisms that determine auditory nerve fiber properties. This approach will help to study general principles of synaptic transmission and specifically to identify the molecular substrates for inherited auditory neuropathies and other cochlear dysfunctions.
Head and Neck Cancer Clinical Trials and Tissue Bank
The Johns Hopkins Head and Neck Cancer Tissue Bank enrolls patients and collects research specimens from Head and Neck Tumor patients, both cancerous and benign, with particular focus on Head and Neck Squamous Cell Cancer patients. It provides specimens to researchers both within the institution and outside.
Laboratory of Vestibular NeuroAdaptation
The Laboratory of Vestibular NeuroAdaptation investigates mechanisms of gaze stability in people with loss of vestibular sensation. A bulk of our research investigates motor learning in the vestibulo-ocular reflex (VOR) using different types of error signals. In addition, we investigate the synergistic relationship between the vestibular and saccadic oculomotor systems as trainable strategies for gaze stability. We are particularly interested in developing novel technologies to assess and deliver improved rehabilitation outcomes. We are validating a hand-held computer tablet for assessment of sensorimotor function and participating in a clinical trial comparing traditional vestibular rehabilitation against a device developed in our laboratory that can unilaterally or bilaterally strengthen the VOR.
Members of the lab include physical therapists, physicians, engineers, statisticians and post-doctoral fellows. The laboratory is supported by generous grant funding from NASA, the NIH, the DOD and grateful patients
The Lin Research Group addresses research questions that lie at the interface of hearing loss, gerontology, and public health. Using a range of methodologies and multidisciplinary collaboration, research broadly focuses on investigating three basic questions pertaining to hearing loss and public health: 1) what are the consequences of hearing loss for older adults?; 2) what is the impact of treating hearing loss on potentially mitigating these outcomes?; and 3) how can hearing loss be addressed from the societal perspective given that nearly 2/3 of all older adults have a clinically-significant hearing impairment?
Dr. Fridman's research group invents and develops bioelectronics for Neuroengineering and Medical Instrumentation applications. We develop innovative medical technology and we also conduct the necessary biological studies to understand how the technology could be effective and safe for people.
Our lab is currently focused on developing the "Safe Direct Current Stimulation" technology, or SDCS. Unlike the currently available commercial neural prosthetic devices, such as cochlear implants, pacemakers, or Parkinson's deep brain stimulators that can only excite neurons, SDCS can excite, inhibit, and even sensitize them to input. This new technology opens a door to a wide range of applications that we are currently exploring along with device development: e.g. peripheral nerve stimulation for suppressing neuropathic pain, vestibular nerve stimulation to correct balance disorders, vagal nerve stimulation to suppress an asthma attack, and a host of other neuroprosthetic applications.
Medical Instrumentation MouthLab is a "tricorder" device that we invented here in the Machine Biointerface Lab. The device currently obtains all vital signs within 60s: Pulse rate, breathing rate, temperature, blood pressure, blood oxygen saturation, electrocardiogram, and FEV1 (lung function) measurement. Because the device is in the mouth, it has access to saliva and to breath and we are focused now on expanding its capability to obtaining measures of dehydration and biomarkers that could be indicative of a wide range of internal disorders ranging from stress to kidney failure and even lung cancer.
Our research is directed toward how the brain controls the movements of the eyes (including eye movements induced by head motion) using studies in normal human beings, patients and experimental animals. The focus is on mechanisms underlying adaptive ocular motor control. More specifically, what are mechanisms by which the brain learns to cope with the changes associated with normal development and aging as well as the damage associated with disease and trauma? How does the brain keep its eye movement reflexes properly calibrated? Our research strategy is to make accurate, quantitative measures of eye movements in response to precisely controlled stimuli and then use the analytical techniques of the control systems engineer to interpret the findings.
Research areas: 1) learning and compensation for vestibular disturbances that occur either within the labyrinth or more centrally within the brain, 2) the mechanisms by which the brain maintains correct alignment of the eyes to prevent diplopia and strabismus, and 3) the role of ocular proprioception in localizing objects in space for accurate eye-hand coordination.
The Systems neurobiology Laboratory is a group of laboratories that all study various aspects of neurobiology. These laboratories include: (1) computational neurobiology Laboratory: The goal of their research is to build bridges between brain levels from the biophysical properties of synapses to the function of neural systems. (2) computational Principles of Natural Sensory Processing: Research in this lab focuses on the computational principles of how the brain processes information. (3) Laboratory for Cognitive neuroscience: This laboratory studies the neural and genetic underpinnings of language and cognition. (4) Sloan-Swartz Center for Theoretical neurobiology: The goal of this laboratory is develop a theoretical infrastructure for modern experimental neurobiology. (5) Organization and development of visual cortex: This laboratory is studying the organization and function of neural circuits in the visual cortex to understand how specific neural components enable visual perception and to elucidate the basic neural mechanisms that underlie cortical function. (6) Neural mechanism of selective visual attention: This laboratory studies the neural mechanisms of selective visual attention at the level of the individual neuron and cortical circuit, and relates these findings to perception and conscious awareness. (7) Neural basis of vision: This laboratory studies how sensory signals in the brain become integrated to form neuronal representation of the objects that people see.
Research in the Vestibular NeuroEngineering Lab (VNEL) focuses on restoring inner ear function through “bionic” electrical stimulation, inner ear gene therapy, and enhancing the central nervous system’s ability to learn ways to use sensory input from a damaged inner ear. VNEL research involves basic and applied neurophysiology, biomedical engineering, clinical investigation and population-based epidemiologic studies. We employ techniques including single-unit electrophysiologic recording; histologic examination; 3-D video-oculography and magnetic scleral search coil measurements of eye movements; microCT; micro MRI; and finite element analysis. Our research subjects include computer models, circuits, animals and humans. For more information about VNEL, click here.
VNEL is currently recruiting subjects for two first-in-human clinical trials:
1) The MVI Multichannel Vestibular Implant Trial involves implantation of a “bionic” inner ear stimulator intended to partially restore sensation of head movement. Without that sensation, the brain’s image- and posture-stabilizing reflexes fail, so affected individuals suffer difficulty with blurry vision, unsteady walking, chronic dizziness, mental fogginess and a high risk of falling. Based on designs developed and tested successfully in animals over the past the past 15 years at VNEL, the system used in this trial is very similar to a cochlear implant (in fact, future versions could include cochlear electrodes for use in patients who also have hearing loss). Instead of a microphone and cochlear electrodes, it uses gyroscopes to sense head movement, and its electrodes are implanted in the vestibular labyrinth. For more information on the MVI trial, click here.
2) The CGF166 Inner Ear Gene Therapy Trial involves inner ear injection of a genetically engineered DNA sequence intended to restore hearing and balance sensation by creating new sensory cells (called “hair cells”). Performed at VNEL with the support of Novartis and through a collaboration with the University of Kansas and Columbia University, this is the world’s first trial of inner ear gene therapy in human subjects. Individuals with severe or profound hearing loss in both ears are invited to participate. For more information on the CGF166 trial, click here.
The mission of the laboratory of vestibular neurophysiology is to advance the understanding of how the body perceives head motion and maintains balance - a complex and vital function of everyday life. Although much is known about the vestibular part of the inner ear, key aspects of how the vestibular receptors perceive, process and report essential information are still mysterious. Increasing our understanding of this process will have tremendous impact on quality of life of patients with vestibular disorders, who often suffer terrible discomfort from dizziness and vertigo.
The laboratory group's basic science research focuses on the vestibulo-ocular reflexes - the reflexes that move the eyes in response to motions of the head. They do this by studying the vestibular sensors and nerve cells that provide input to the reflexes; by studying eye movements in humans and animals with different vestibular disorders, by studying effects of electrical stimulation of vestibular sensors, and by using mathematical models to describe these reflexes. Researchers are particularly interested in abnormalities of the brain's inability to compensate for vestibular disorders.