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 for a bioinformatics postdoctoral fellow to join our group in 2017 or earlier. The successful candidate has a PhD in bioinformatics or computational biology. Strong interest and creative ability in data presentation, computer animation, and enthusiasm for bioart/biocreativity is a requirement. We expect strong work ethics, vision, and ability to independently learn and implement new technologies.
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
Please contact me at least one year in advance of your desired start date. Postdocs who have been doing well in my group bring exceptional motivation, clear communication skills, creativity, focus, and independence. I encourage every single postdoc to apply for independent fellowships. Stanford has strict rules on minimizing lengthy postdoctoral stints and discourages applications of candidates who already have more than 2 years experience.
We currently welcome graduate students. If you are already at Stanford and interested in rotating with us, please email me. If you are interested in the Stanford graduate programs, please read about the requirements at the Stanford Biosciences website. We are affiliated with all home programs. Please list me as a potential advisor when applying and please send me an email to introduce yourself.
Please contact me at least one year in advance of your desired start date. Our research topics, historically, have been complex and require at least 2 years of dedicated focus. Postdocs on these short stints who have been doing well in the past were especially motivated, creative, and highly independent. You are expected to successfully apply for an independent full fellowship before you start in the lab. We rarely have funds to supplement fellowships.
We occasionally accept high school students for summer internships and encourage interested students to consult the Science Outreach programs website. We only accept students who successfully applied to one of the official Stanford programs such as SIMR. If you are interested in such an internship, please contact Dr. Heller in early January. Please note that most of the Stanford programs favor local high schools.
Who are we?
• Ealy, M., Ellwanger, D.C., Kosaric, N., Stapper A.P. & Heller, S. Single-cell analysis delineates a trajectory toward the human early otic lineage. Proceedings of the National Academy of Sciences of the United States of America, 113, 8508-8513 (2016). http://www.pnas.org/content/early/2016/07/08/1605537113
Congratulations to Megan, Daniel, Andres, and Nina. This manuscript is the product of 3 years of hard work by Megan. The initial idea was to control the culture conditions of human pluripotent stem cells in a way that minimizes “random” signals among cells. We hypothesized that monolayer cultures in defined conditions would allow us to guide the stem cells in a somewhat synchronous manner with the ultimate goal of generating early inner ear precursor cells. We found that this idea, in theory, works well for the early stages of generating the type of tissue that eventually gives rise to the early stages of the inner ear. What we also realized is, however, that the complex 3-dimensional development of the inner ear as it occurs in the embryo might require a corresponding 3-dimensional environment in the culture dish. Our story depicts the existing limitations and difficulties for guiding human pluripotent stem cells towards the inner ear lineage. I believe that this could contribute to the development of novel strategies for generating human inner ear cells in vitro. It also illustrates that it is a very difficult problem to control the development of a complex cell lineage and highlights the need for novel solutions for this problem. I am thankful to the editor and the reviewers that they accepted our interpretation of the results and allowed us to publish this “open ended” outcome of a research project in the PNAS. Innovative data analysis and the idea to compare otic cell phenotypes between human and mouse most certainly helped us to make the manuscript appealing to a more general audience.
• DeJonge, R.E., Liu, X.P., Deig, C.R., Heller, S., Koehler, K.R., and Hashino, E. Modulation of Wnt signaling enhances inner ear organoid development in 3D culture. PLoS One, 11: e0162508 (2016). http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162508
Generation of sensory hair cells from mouse embryonic and induced pluripotent stem cells is a tricky endeavor. The cells want to become lots of other things and keeping them on track has been a challenge for many researchers. In this research led by Karl Koehler and Eri Hashino at Indiana University, and conducted by Rachel DeJonge and other members of the Koehler and Hashino labs, it is shown that addition of a small chemical compound (a Wnt signaling agonist) at a specific time point of the cell guidance protocol substantially improves the yield of inner ear cells. Our laboratory has made similar observations and we contributed tools (a cell line) and some intellectual input to the story. Eri and Karl have really shown in recent years that it is possible to reliably generate inner ear cells, including functional hair cells, from embryonic stem cells. I am happy that our lab was inspiring for this by laying the groundwork specifically with our papers published in 2003 and 2010.
• Cao, J.M., Cheng, X.N., Li, S.Q., Heller, S., Xu Z.G., She, D.L. Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity. Scientific Reports, 6: 36739 (2016). http://www.nature.com/articles/srep36768
Almost 10 years ago, Heller lab postdoc Zhigang Xu, one of the senior authors of this paper and now leading his own lab at the School of Life Sciences at Shandong University, started to search for protein complexes in hair cell stereocilia. For this, he extensively screened inner ear yeast 2-hybrid libraries and he identified several interesting genes and potentially interacting proteins that might play a role in hair cell function. Myosin18A was one of the proteins that interested him. We never thought that this initial project and the protein interaction partners that he identified during his postdoc at Stanford would lead him to muscle development in zebrafish. Congratulations to Zhigang and his collaborators to this very meticulously done research.
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