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 depicts the embryonic mouse inner ear stained with an antibody to a protein that is specifically expressed in the otic lineage. Postdoctoral fellow Byron Hartman is working on this ongoing project and provided this spectacular image.
We are actively looking to hire a postdoctoral fellow or research associate with substantial experience in computational biology as well as knowledge of computer graphics and strategies for analysis of high dimensional data. The new team member needs to be exceptionally creative and motivated to apply his/her computational training toward solving biologically relevant questions.
Similarly, we are looking for a postdoctoral fellow to join our group in mid 2015 or later. The successful candidate should have a strong interest in solving open questions how fate decisions in the developing and regenerating inner ear are being orchestrated. We expect strong work ethics, creativity, and ability to independently learn and implement new technologies. A background in bioinformatics or interest in computational analysis methods of single cell transcriptome data is a requirement.
If you are interested in joining our group, please send a single introductory paragraph and your CV to Stefan Heller at firstname.lastname@example.org
• Durruthy-Durruthy, R., Gottlieb, A., Hartman, B.H., Waldhaus, J., Laske, R.D., Altman, R. & Heller, S. Reconstruction of the Mouse Otocyst and Early Neuroblast Lineage at Single Cell Resolution. Cell (2014). http://http://www.cell.com/cell/abstract/S0092-8674(14)00411-5
We started this project about 1½ years ago and as outlined in the blog post of Apr 24, this paper marks a new focus and direction of research in our laboratory. This focus builds on single cell analysis technology to address important questions in development and regeneration. The history of this manuscript is short (thank god!): The manuscript went directly to Cell in early Dec 2013 and we received the reviews in early Feb 2014. Generally, one would not be happy when it takes 8 weeks to review a manuscript, but there were the holidays and we knew that we had submitted a very long manuscript with plenty of supplementary information, so it was understandable that it took a while. We were happy when we received the reviews: the editor and reviewers really liked the story and we had only to address a few minor critiques plus the task of shorting the text by about 25% so that it fits with the space requirements of the journal. We would like to thank the anonymous reviewers for being excited and supportive of this work. For the laboratory, this paper is surely something special.
• Ronaghi, M., Nasr, M., Ealy, M., Durruthy-Durruthy, R., Waldhaus, J., Diaz, G.H., Joubert, L.M., Oshima, K. & Heller, S. Inner Ear Hair Cell-Like Cells from Human Embryonic Stem Cells. Stem cells and development (2014). http://www.ncbi.nlm.nih.gov/pubmed/24512547
In this first publication of 2014, we show that it is generally possible to guide human embryonic stem cells toward the inner ear lineage and to generate otic progenitor cells that can differentiate into hair cell-like cells. We also uncovered many limitations of the technology that need to be addressed in future research. Overall, this paper is the product of many years of hard research; quite a difficult project, when compared to other fields such as generation of neurons or muscle cells. History of the paper and review process: We started with submitting the manuscript to PNAS and Stem Cells. Both journals did not review the manuscript, perhaps because we were very clear that the technology has certain limitations. Rewriting parts of the Abstract and Discussion as well as pointing out to the editor of Stem Cells & Development that this paper is the first one to describe the generation of human inner ear sensory hair cells from embryonic stem cells helped. Two reviewers were very positive and the manuscript was accepted after minor revisions.
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