Zheng, Jing, PhD
Otolaryngology; Hugh Knowles Center Fellow
Searle 12-490 Chicago
|Areas of Research||
Cell Biology, Hearing Sciences, Molecular Neuroscience
|NU Scholar Profile|
|Recent Publications on PubMed|
The goal of my lab is to identify and investigate molecules that play important roles in mammalian hearing, thus to enrich our understanding of cochlear physiology, and to further develop a better strategy to prevent hearing loss.
Molecular basis of cochlear amplification. OHCs undergo rapid somatic length changes when the voltage across their membrane is altered. This unique somatic electromotility provides the local mechanical amplification of the cochlear response to sound. Without OHCs, hearing threshold is elevated by 40-50 dB and frequency resolution deteriorates. Prestin is the motor protein of OHCs and it is required for cochlear amplification (Zheng et al., Nature, 2000). Coincidently, prestin is only expressed in OHCs, which are also the most vulnerable cells in the organ of Corti. In the past, studying OHC amplification mechanisms and preventing OHC loss were considered as two separate research fields. However, our recent data indicate a close connection between prestin’s function and the vulnerability of OHCs to a variety of ototoxic exposures. To understand this link, we focus on investigating the molecular mechanism of motor protein prestin using various cellular, biochemical and molecular biological methods including high throughput small molecule compound library screening procedures. We also investigate prestin-associated proteins (VAPA, oncomodulin, and CFTR) as well as cell death pathways associated with OHCs.
Protein network of hair cells. Connections between OHC cilia and tectorial membrane (TM) are required for delivering OHC mechanical feedback and thereby amplification. However, little is known about the molecular basis of OHC-TM connections. We recently identified a new secreted protein called CEACAM16 from mammalian cochleae (Zheng e al. PNAS, 2011). CEACAM16 proteins localize to the tips of the tallest stereocilia of OHCs and the tectorial membrane (TM). This specific localization suggests a role in maintaining the integrity of the TM, as well as in the connection between the OHC stereocilia and TM. We discover that ceacam16 is a -tectorin-interacting protein that concentrates at the point of attachment of the TM to the stereocilia, and when mutated, results in an autosomal dominant non-syndromic deafness at the DFNA4 locus. We are in the process of investigating CEACAM16‘s function in CEACAM16 knockout mouse model and expanding our knowledge of the molecular basis for building and maintaining OHC-TM connections.