UVA Neuroscience Graduate Program

Hearing loss is America’s leading disability, affecting millions of people of all ages. To develop preventative and restorative clinical approaches, it is crucial to understand how the hearing process works on the cellular and molecular level. Hearing is mediated by specialized hair cells in the inner ear, and the goal of our lab is to learn more about their function: how do hair cells develop, what proteins are they made of, and what are the molecular mechanisms of their dysfunction that cause hearing loss and balance defects? To this end, we use a variety of techniques to identify and characterize proteins involved in hair cell function.

Our lab combines Proteomics and Genomics to identify proteins and genes that are involved in hearing and deafness. Using this multi-faceted approach, we have already identified several genes that are involved in hearing loss (e.g. FSCN2), and we are currently working on several novel genes with possible roles in hearing and deafness.

Our lab is especially interested in the question of how the hair cell maintains its integrity over the years.  Hair cells are among the cell types that cannot be renewed and therefore require a special maintenance strategy. Our hypothesis is that hair cells maintain their functionality by constantly turning over its proteins, and we use metabolic labeling in combination with peptide mass spectrometry to measure protein turnover in hair cells. We are especially interested in changes that occur during pathological stress situations (mechanical and oxidative stress). 

Another focus of our lab is the dynamic behavior of hair cell proteins, especially components involved in the mechanotransduction process. We want to describe the subcellular movements of proteins that are involved in establishing and executing the mechanotransduction process, using in-vivo imaging. We will generate transgenic Xenopus frogs that express GFP-tagged proteins in hair cells and monitor the movement of these proteins in the living hair cell. We are especially interested in observing the dynamic processes associated with the disruption of the transduction complex caused by cellular stress situations, such as oxidative and mechanical stress.

• Jung-Bum Shin, Chantal M. Longo-Guess, Leona H. Gagnon,Katherine W. Saylor,Rachel A. Dumont,Kateri J. Spinelli,James M. Pagana,Phillip A. Wilmarth,Larry L. David,Peter G. Gillespie,and Kenneth R. Johnson
• Jung-Bum Shin, James Pagana, Peter G. Gillespie. Twist-off purification of hair bundles. Methods Mol Biol. 2009; 493: 241-56.
• Jung-Bum Shin, Femke Streijger, Andy Beynon, Theo Peters, Laura Gadzala, Debra McMillen, Cory Bystrom, Catharina E. Van der Zee, Theo Wallimann, Peter G. Gillespie. Hair bundles are specialized for ATP delivery via creatine kinase. Neuron. 2007; 53(3):371-86.
• Leona H. Gagnon, Chantal M. Longo-Guess, Mark Berryman, Jung-Bum Shin, Katherine W. Saylor, Heping Yu, Peter G. Gillespie, and Kenneth R. Johnson. The chloride intracellular channel protein CLIC5 is expressed at high levels in hair cell stereocilia and is essential for normal inner ear function. J Neurosci. 2006; 26(40):10188-98.
• Jung-Bum Shin, Dany Adams, Martin Paukert, Maria Siba, Samuel Sidi, Michael Levin, Peter G. Gillespie, and Stefan Gründer. Xenopus TRPN1 (NOMPC) localizes to microtubule-based cilia in epithelial cells, including inner ear hair cells. Proc Natl Acad Sci U S A. 2005; 102 (35):12572-7.