Hearing Research ProgramApproximately 30 million Americans suffer from varying degrees of hearing loss. Hearing loss affects individuals of all ages and is one of the most common conditions affecting older adults. Individuals with profound hearing loss are considered deaf. In the majority of cases hearing loss is due to abnormal development or injury to sensory cells harbored in the hearing organ within the inner ear called cochlea. Highly complex in function, cochlea is nevertheless highly ordered in morphology. Rows of sensory ‘hair' cells are studded in an orderly fashion within the spiral ‘staircase' of the cochlear duct. The hallmark of the sensory cell is a tuft of hair-like projections on the apical surface of the cell, hence the name ‘hair cell'. These hair cells are exquisite sensors with great adaptability that enable the subject to respond to a whisper, enjoy a concert or hear a child talk in a crowd. Genetic predisposition, age, noise, ototoxic drug or a combination of these factors can affect hair cells resulting in hearing loss. The hearing loss is permanent in many cases because affected hair cells degenerate and are not replaced.
Learn moreMolecular OtologyRole of Protocadherins in hearing and deafness
The first project focuses on the mouse mutation Ames waltzer (av). The mouse av is a recessive mutation, which causes deafness and vestibular dysfunction associated with degeneration of the inner ear neuroepithelia. The gene that harbors the av mutation was identified as a protocadherin, Pcdh15. Subsequent work showed that mutation in the human homologue of the mouse Pcdh15 causes Usher syndrome type 1F, establishing the av mouse as a model for deafness in USH1F. Using the mouse model, we are trying to uncover the role of Pcdh15 in the normal development of hearing function.
Learn moreNoise-Induced Hearing LossThe National Institutes of Occupational Safety and Health (NIOSH) and the NIH recognize noise-induced hearing loss as a significant problem. A quick survey of the literature shows that there is lot of information on the physiological and anatomical changes in mice, rats and guinea pigs, following noise exposure. However, the molecular mechanism underlying noise-induced hearing loss (NIHL) remains to be fully understood. Our aim is to identify pathways associated with NIHL using specific inbred strains of the laboratory mouse. We are using an approach that would target cells within functional domains of the cochlea. Global expression profiling of cells of the organ of Corti and spiral ganglion following noise exposure will be used to identify pathways induced or influenced by NIHL.
Learn moreHair Cell Biology & RegenerationThe hair cell is an exceptionally sensitive and alacritous mechanoreceptor that is essential not only for hearing but also for balance and for the detection of water movement by aquatic vertebrates . This receptor represents mechanical stimuli as electrical responses that are relayed to the brain . Physiologically, hair cells are very well understood and much is known about how they function in hearing. However, to understand the molecular basis of hearing, the genes expressed in the hair cell must be identified and their role in hearing evaluated. Researchers in the Department of Otolaryngology at Case Western Reserve University have developed a functional genomics approach involving the zebrafish ( Danio rerio ) model system that utilizes DNA oligonucleotide microarrays and reverse genetics. This research is focused on three aspects of the hair cell: hair-bundle morphogenesis and operation, hair-cell innervation, and ribbon synapse formation and function. These studies additionally integrate imaging, physiological, transgenic, and behavioral approaches to study the hair cell.
Learn moreOtitis MediaMiddle ear infection or otitis media (OM) accounts for more than 30 million clinical visits annually with a cost of 5 billion dollars/per year in the U.S. The hearing loss associated with OM can cause developmental problems, including delayed language skills. The widespread use of oral antibiotics to treat OM has resulted in a dramatic increase in antibiotic-resistance of the bacterial strains that cause OM , as well as other potentially fatal diseases including pneumonia, meningitis and septicemia. The molecular mechanisms by which bacteria cause overactive host responses are still unclear. Vaccine development still remains a great challenge. There is an urgent need for developing novel therapeutic strategies against OM. However, genetic and genomic technologies hold tremendous promise for the development of new strategies that could dramatically impact this major health problem.
Learn moreAuditory ProteomicsMouse models have been used extensively to understand the genetic basis of hearing loss in humans. However, a review of the literature shows that few auditory proteomic studies have been undertaken with mouse models. Identifying the genes associated with hearing loss is an important first step. However, since proteins are intimately connected with the physiology (or at the ‘business end') of the organ, identifying the protein associated with hearing loss will be critical in finding a cure for hearing impairment in humans. Proteomics is now considered to be a priority and many in the hearing research field are going to look for that “complementary and critical” information at the protein level in their favorite mouse model. For many of these investigators, the availability of a proteome atlas of the mouse cochlea at various postnatal ages' in common inbred strains would be extremely valuable (save time and resources). There is a great need to generate a comprehensive proteome atlas of the cochlea and the laboratory mouse is an excellent model for mammalian cochlea. The generation of a proteome atlas would simplify the task of analyzing changes in protein expression and modifications as a function of development and disease, which is of great importance to researchers in the auditory field.
Learn moreMicrosensors
Attempt to regenerate hair cells is an important goal in hearing research. Some progress has been made in the recent past that gives us hope that hair cell regeneration is possible. However, it is going to be long time before we can generate a full complement of hair cells to replace damaged/lost hair cells in the inner ear. Prosthetic devices such as Cochlear Implant (CI) restore some degree of hearing function to those who suffer from severe to profound hearing loss. CI is an artificial hearing device, designed to produce useful hearing sensation by electrically stimulating nerves inside the inner ear through electrode array. CI represents a significant improvement compared to the old-fashioned hearing aids in terms of speech recognition but it is far from restoring normal hearing. This project will address the following question: can we create microdevices that would respond to specific frequencies like hair cells? We are trying to design a micro device that will act as a mechanotransducer. We are currently carrying out ‘engineering feasibility' test.
Learn moreMolecular Anatomy of Head & Neck CancerSquamous cell carcinoma of the head and neck (HNSCC) is a major problem and is often associated with poor survival and morbidity rates. Early diagnosis plays a key role in disease progression, treatment response, and ultimately, quality of life and patient survival. Elucidation of the molecular mechanisms leading to head and neck cancer may result in the identification of new biomarkers, such as expression of specific genes or proteins, which would be of diagnostic and prognostic value, and may aid in the clinical management of these patients. The discovery of these biomarkers can also be useful for identification of preneoplastic lesions, which are difficult to distinguish from other lesions. Such knowledge will be of great value in the prevention and prognosis of HNSCC.
Learn morePhotodynamic TherapyPhotodynamic therapy involves the use of a photosensitizing chemical which induces cell destruction when activated by a specific wavelength of light. Selective cellular uptake of these chemicals could be used to treat various epithelial disorders. The objective of this experiment is to evaluate photodynamic therapy using the photosensitizer pthalocyanine on cottontail rabbit papilloma virus induced tumors of rabbit epithelium previously transplanted to severe combined immunodeficient (SCID) mice. This experiment will serve as an animal model for the treatment of recurrent respiratory papillomatosis in humans.
Learn moreTissue EngineeringThe goal of this project is to utilize computer-aided design and injection molding technologies to tissue engineer precisely-shaped cartilage in the shape of butterfly tympanic membrane patches out of chondrocyte-seeded calcium alginate gels. Molds will be designed with the aid of computer programs and built using synthetic materials utilizing fused deposition modeling. Tympanic membrane patches will be fabricated using bovine articular chondrocytes seeded at high density in calcium alginate gels. Molded patches will be cultured in vitro for up to ten weeks, then assessed biochemically, morphologically, and histologically. We will fabricate cartilage-seeded tympanic membrane patches using cell culture techniques. The patches will then be placed into chinchilla tympanic membrane perforations, and the membranes will be examined histologically after harvesting. The work will be sponsored by Gyrus Corporation.
Learn moreCortical Bone SubstitutesThere is a paucity of mechanically strong and reliable cortical bone substitutes. Autogenous bone is optimal but it can be in short supply and its harvest carries with it the risk of donor site morbidity and infection, and increased operative time. A novel material that has been developed here at the Case Department of Biomedical Engineering uses a collagen scaffold for subsequent mineralization with carbonated apatite to form a nanophase composite, which mimics normal bone architecture and has the mechanical properties necessary for load sharing and even load bearing function immediately upon insertion.
Learn moreFocused Laryngeal StimulationProject 1: Dynamic Vocal Fold Adduction for Bilateral Paralysis
Project 2: Human Laryngeal Pacing for Aspiratio
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