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:
• 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 (2018). 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.
• Hartman, Byron H.; Böscke, Robert; Ellwanger, Daniel C.; Keymeulen, Sawa; Scheibinger, Mirko and Heller, Stefan. Fbxo2VHC mouse and embryonic stem cell reporter lines delineate in vitro-generated inner ear sensory epithelia and enable otic lineage selection and Cre-recombination. Dev Biol, 443; 64-77 (2018). Link to the paper in Dev Biol.
In this paper, we describe a set of tools for generating multicistronic reporter lines that consist of fluorescent proteins, hygromycin selection, and Cre-based lineage labeling. We showcase one version of this toolset with a knock-in mouse model for the Fbxo2 gene, a specific and highly expressed otic lineage marker that Byron discovered and originally described a while back. The knock-in mouse model validated the already published gene expression pattern for Fbxo2 and moreover, it revealed additional details. Interestingly, Byron found that inner ear organoids, generated from Fbxo2VHC mouse embryonic stem cells (ESCs) showed exceptionally strong Venus-fluorescence labeling of sensory epithelia cells and their progenitors. This reporter mouse and the ESCs from this mouse model are therefore quite useful tools for a number of follow up experiments such as enrichment of stem cell-based progenitors and more in-depth characterization of the transcriptomic phenotype of otic progenitor cells.
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