Jung-Bum Shin

Shin, Jung-Bum

Primary Appointment

Associate Professor, Neuroscience


  • BS, Biochemistry, University of Tubingen
  • PhD, Neuroscience, Free University of Berlin
  • Postdoc, Hearing Research, Oregon Health Sciences University

Contact Information

Nueroscience Dept., MR4 -Room # 5144
409 Lane Road
Charlottesville, VA 22908
Telephone: 434-924-1289
Fax: 434-982-4380

Research Disciplines

Biochemistry, Biotechnology, Cell and Developmental Biology, Molecular Biology, Neuroscience

Research Interests

Auditory Neurobiology

Research Description

Repair of the stereocilia actin core (project leader: Elizabeth Wagner)
Hair bundles are complex structures that have to be maintained throughout the life of the organism, because mature mammalian hair cells cannot be regenerated. Therefore, there are likely many mechanisms in place to repair the damage that builds up over time from the constant mechanical stress to which hair cells are exposed. My research primarily focuses on the repair of the F-actin-based stereocilia cores, which can be damaged by loud noise. The damaged sites appear as gaps in phalloidin staining of F-actin. Other groups have shown that monomeric actin and F-actin associated factors are enriched at these sites, suggesting that they are being repaired by localized F-actin remodeling. Supporting this hypothesis, I have shown that the number of phalloidin-negative gaps decrease to levels no longer significant from baseline within one week of exposure to damaging noise. Additionally, by labeling newly synthesized actin following noise exposure, I have shown the incorporation of discrete patches of F-actin along the length of the stereocilia core, which we propose to be sites of repaired damage.
I also am interested in determining the mechanism by which stereocilia F-actin is repaired. We have several pieces of evidence suggesting that a protein known as XIRP2 is involved in the process. First, XIRP2 immunostaining is enriched at phalloidin-negative gaps in stereocilia. Second, Xirp2-null mice develop large numbers of phalloidin-negative gaps in the absence of noise overstimulation, suggesting they are building up over time in the absence of efficient repair. And finally, XIRP2 seems to be required for the repair of gaps, because, unlike in wild type mice, the number of gaps following noise exposure does not decrease back to baseline levels following loud noise exposure in Xirp2-null mice.
Currently I am working to determine the mechanism by which XIRP2 is involved the repair of gaps. Preliminary evidence suggests that monomeric g-actin is less efficiently recruited to damaged sites in the absence of XIRP2. I also plan to determine whether other F-actin associated factors are less enriched in gaps in Xirp2-null mice and whether XIRP2 directly interacts with any of these factors.

Myosin-VIIA (Myo7a) in tip link tension (project leader: Sihan Li)
Mutations in myosin-VIIa (MYO7A) cause Usher syndrome type 1, characterized by combined deafness and blindness. MYO7A is proposed to function as a motor that tensions the hair cell mechanotransduction (MET) complex, but conclusive evidence is lacking. We made the surprising discovery that multiple MYO7A isoforms are expressed in the mouse cochlea. In mice with a specific deletion of the canonical isoform (Myo7a-ΔC mouse), MYO7A is severely diminished in inner hair cells (IHCs), while expression in outer hair cells is affected tonotopically. IHCs of Myo7a-ΔC mice undergo normal development, but exhibit reduced resting open probability and slowed onset of MET currents, consistent with MYO7A’s proposed role in tensioning the tip link. Mature IHCs of Myo7a-ΔC mice degenerate over time, giving rise to progressive hearing loss. Taken together, our study reveals an unexpected isoform diversity of MYO7A expression in the cochlea and highlights MYO7A’s essential role in tensioning the hair cell MET complex.
In continuing studies, we are investigating the presence and functional relevance of other isoforms of MYO7A in hair cells. We are also interested in identifying the cis- and trans-factor that regulate the cell-type specific expression of the various MYO7A isoforms.

Cuticular plate in hair cell function (project leader: Tingting Du)
A more recent interest concerns molecules (e.g. LMO7) that are indispensable for the integrity of the cuticular plate, which provides the mechanical foundation for the hair bundle.

Repair of the hair cell mechanotransduction complex:
A long-standing interest of the lab has been the repair of the tip link and mechanotransduction (MET) complex. Our most recent work has established that myosin-VIIa is the tip link motor that provides tension to the MET complex and is essential for the sensitivity of hearing. Our next step is to study the mechanisms that mediate the repair of the tip link and MET complex, which can be damaged by external stresses such as age and noise.

Selected Publications