Our laboratory works on inner ear development and regeneration, as well as on the biology of sensory hair cells, the mechanosensitive cells of the inner ear. We are located at Stanford University in the School of Medicine and affiliated with the Otolaryngology department. We are proudly affiliated with the Stanford Initiative to Cure Hearing Loss and we thank all supporters of this endeavor.
We are interested how the inner ear develops from an early anlage called the otic placode. Our goal is to describe the otic lineage from an early placodal progenitor until it splits up in multiple cell types making up the sensory epithelia, innervating ganglia, and accessory structures.
In parallel, we apply knowledge we gained from guiding embryonic and induced pluripotent stem cells along the otic lineage to find ways for treatment of hearing loss. This involves identification of mechanisms of sensory hair cell regeneration in animals such as chickens that recover naturally from hearing loss, screening for potential regenerative targets that can be activated with drugs, and exploring reprograming as well as cell transplantation strategies.
The image shown above is an artistic view of E15 utricle hair bundles overlaid with CellTrails-inspired art. SEM credit goes to Rachel Dumont and Peter Barr-Gillespie (OHSU and the Vollum Institute). CellTrails maps and artistic rendering was done by Daniel Ellwanger.
We are currently looking for a Stanford Undergraduate Student who wants to join us for a 1-2 year ongoing part-time research project. We are asking for a 6-10 hours per week commitment and offer the opportunity to do full time research during the summer months (2020, 2021). We expect strong work ethics, a certain level of independence, and strong interest in laboratory science.
If you are interested in joining our group, please send a single introductory paragraph and your CV to Dr. Marie Kubota and Dr. Stefan Heller: kubomari[at]stanford.edu and hellers[at]stanford.edu
Who are we?
Current Laboratory Members:
• Zhu, Ying; Scheibinger, Mirko; Ellwanger, Daniel C.; Krey, Jocelyn F.; Choi, Dongseok; Kelly, Ryan T.; Heller, Stefan and Barr-Gillepie, Peter G. Single-cell proteomics reveals changes in expression during hair-cell development. eLIFE, 8:e50777 (2019) Link to the paper.
This continuation of our collaboration with the Barr-Gillespie laboratory is – to our knowledge – the first single cell proteomics study that uses bioinformatics trajectory analysis. This work was made possible by a major technological advance contributed by Ryan Kelly’s laboratory at Pacific Northwest National Laboratory that allows all the steps for a proteomic workup of a single cell to be done in very small containers, so-called nanoPOTS. This collaborative effort led to the identification of TMSB4X an actin monomer sequestering protein that dynamically changes expression precisely when hair bundle formation in developing hair cells is being triggered. This, in turn, results in an increase of available G-actin for bundle assembly. The maturing hair cell is able to perform such a logistic feat without massively changing expression of actin. One could imagine an “unpacking” of already available parts that then become available for assembly of larger structures.
• Janesick, Amanda S. and Heller, Stefan. Stem Cells and the Bird Cochlea – Where is Everybody? Cold Spring Harbor Perspectives in Medicine, doi: 10.1101/cshperspect.a033183 (2019); 9 (4). Link to the paper.
In this perspective, we describe different mechanisms of hair cell regeneration in the avian cochlea and argue that there is no doubt that cochlear hair cell regeneration in birds is driven by stem cells. With all this evidence for stem cells, the question remains: Where are they? This short essay pretty much outlines the need for a thorough analysis of hair cell regeneration in the bird inner ear.
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