AHRF Funds Six Projects for 2010

For 2010, the American Hearing Research Foundation will be funding six grants. This year, we received the highest number of grant proposals in our history—41 proposals in all. The following grants will begin on January 1, 2010, and will be funded for $20,000 for one year.

Nicole Schmitt, M.D.
University of Washington, Seattle
“Significance of tumor necrosis factor alpha in cisplatin ototoxicity in Vivo”

Douglas Cotanche, Ph.D.
Boston University School of Medicine, Massachusetts
“Cell fate regulation in cochlear development and regeneration”

Anand Mhatre, Ph.D.
New York University, New York
“Biological role of nonmuscle myosin IIA in sensory hair cells”

Saima Riazuddin, Ph.D.
Cincinnati Children’s Hospital Medical Center, Ohio
“Generation and characterization of a mouse model of DFNB26”

Angelika Doetzlhofer, Ph.D.
Johns Hopkins University School of Medicine, Baltimore, Maryland
“Response of supporting cell to hair loss in the mammalian cochlea”

Sharba Bandyopadhyay, Ph.D.
University of Maryland, College Park
“Alterations in neural processing in the auditory cortex with early noise induced hearing loss”

Nicole Schmitt, M.D.

University of Washington, Seattle
“Significance of tumor necrosis factor alpha in cisplatin ototoxicity in Vivo

Cisplatin is a common chemotherapy drug used to treat cancer that often has the side effect of causing hearing loss in the higher frequencies. The hearing loss is due to the loss or damage of outer hair cells in the cochlea. It is thought that the cisplatin causes oxidative stress within the hair cells to cause them to enter apoptosis, or programmed cell death. One of the downstream factors that is triggered by cisplatin is a pro-inflammatory chemical called tumor necrosis factor alpha (TNF-alpha). In test tube studies, it has been shown that TNF-alpha plays an important role in ototoxicity. Schmitt and colleagues will investigate the role of TNF-alpha in animals. They will use mice to determine the location of TNF-alpha generation in the mouse cochlea after administration of cisplatin, and also investigate the level of toxicity caused by cisplatin in mice that do not produce TNF-alpha, and in mice that overproduce TNF-alpha.

Douglas Cotanche, Ph.D.

Boston University School of Medicine, Massachusetts
“Cell fate regulation in cochlear development and regeneration”

Birds can regenerate hair cells in the cochlea once they are lost – an ability that mammals do not possess. When hair cells are lost in birds, following loud noise exposure or administration of ototoxic drugs in the lab, the supporting cells around the hair cells turn into new hair cells. Cotanche and colleagues hope that by studying this process in birds, they will be able to induce the mammalian cochlear cells to undergo a similar regeneration. Specifically, the researchers will study the genetics involved in supporting cell transduction into hair cells in chicks and mice. They hope to gain understanding of the molecular processes involved in hair cell regeneration in order to cause the same regeneration in mammalian cells.

Anand Mhatre, Ph.D.

New York University, New York
“Biological role of nonmuscle myosin IIA in sensory hair cells”

Myosin is a cellular structure normally found in muscles, but it is also found in other cells and often serves as a structural scaffolding for the cell. A gene called MYH9 produces a nonmuscle myosin protein called NMHC-IIA. Mutations in this gene have been linked to hereditary hearing loss. NMHC-IIA has been found in adult mouse sensory hair cells. Mhatre and colleagues want to study how the complete loss of the MYH9 gene would affect hearing in mice, but aniomals without this gene die as embryos. To get around this problem, the researchers will inactivate the MYH9 gene post-natally within the ear. They will be able to test their hypothesis that the loss of NMHC-IIA (after birth) will disrupt the structural and/or functional integrity of sensory hair cells and will result in hearing loss. The results of this study will provide insight into the role of NMHC-IIA in the sensory hair cells and the mechanism of hearing loss caused by its dysfunction.

Saima Riazuddin, Ph.D.

Cincinnati Children’s Hospital Medical Center, Ohio
“Generation and characterization of a mouse model of DFNB26″

More than 100 gene locations have been indentified as contributing to hearing loss in its various forms. However, knowledge on how genes affect hearing remain inadequate. Researchers need to be able to study and develop animal models to study disease causing mutations, and to define the molecular pathways leading to hearing loss to ultimately develop therapeutic approaches to treating deafness. Riazuddin and colleagues have recently mapped a deafness causing gene called DFNB26 in an extended family. They also discovered another gene that that suppresses the deafness-causing gene. The researchers hope to study how these two genes work to cause and prevent deafness among the members of this family by developing mice with these genes. The study will provide valuable models for defining the role of DFNB26 in the inner ear and to develop treatment strategies for this disease.

Angelika Doetzlhofer, Ph.D.

Johns Hopkins University School of Medicine, Baltimore, Maryland
“Response of supporting cell to hair loss in the mammalian cochlea”

Doetzelhofer and colleagues hope to uncover the molecular signals activated in supporting cells after hair cell loss, and what pathways may inhibit hair cell regeneration. In mammals, hair cells only develop during embryonic development, and when hair cells are lost, they are not replaced. However, in birds, when hair cells are lost, supporting cells can transform into new hair cells. Researchers believe that supporting hair cells, even in mammals, have the ability to transform into hair cells, but that signals from adjacent cells and/or dying hair cells block supporting cells from becoming new hair cells. Doetzlhofer and colleagues will investigate these inhibitory pathways and will look at changes in gene expression in supporting cells as hair cells are lost. Understanding the molecular mechanisms that prevent hair cell regeneration in mammals is a crucial first stem in developing successful hair cell replacement therapies.

Sharba Bandyopadhyay, Ph.D.

University of Maryland, College Park
“Alterations in neural processing in the auditory cortex with early noise induced hearing loss”

Bandyopadhyay and colleagues will investigate how areas of inhibitory and excitatory neurons in the auditory cortex change due to early sensorineural hearing loss (SNHL). Understanding changes in these areas after early SNHL will help to uncover mechanisms leading to altered perception of sound. These discoveries will help to design better hearing aid algorithms and cochlear implant stimulation paradigms that take these changes in auditory processing into account.