Heller Laboratory
Stanford University

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About our Research

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 affiliated with the following graduate and fellowship programs: Biology, Developmental Biology, Genetics, Molecular & Cellular Physiology, Neurosciences, Bioengineering, and Stem Cell Biology & Regenerative Medicine. If you are interested in rotating with us, please stop by the lab/office any time!

 

Joining our Lab

We are looking for a bioinformatics postdoctoral fellow.  The successful candidate has a PhD in bioinformatics or computational biology.  Strong interest in single cell trajectory analysis, 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 hellers@stanford.edu

 

If you are interested in joining the lab, please find details and additional information here.

 

What we do?

We are focusing on three main questions.

More about us

How about Some Fun Facts about our laboratory?

7
Backpacking trips to the Utah desert
18
years since we began in Boston in 2000
19
Countries represented in the last 16 years in the lab
100%
of group members came back from lab desert hiking trips

Plenty of open questions in inner ear biology: how hearing really happens? Can we cure hearing loss?

Who are we?

Heller Laboratory

April 2018

Current Laboratory Members:

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Stefan Heller

PI
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Amanda Janesick

Post-Doctoral Researcher
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Ben Woodruff

CIRM Bridges Intern Student
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Byron Hartman

Research Associate
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Daniel Ellwanger

Post-Doctoral Researcher
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Giovanni Diaz

Graduate Student
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Jiwon Chang

Visiting Assistant Professor
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Marie Kubota

Post-Doctoral Researcher
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Mirko Scheibinger

Post-Doctoral Researcher
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Nesrine Benkafadar

Post-Doctoral Researcher
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Sabine Mann

Laboratory Manager
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Tom Pritsky

Undergraduate Student
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Alumni

Previous Labmembers

How about Some Fun Facts?

261
Sunny days annually, on average in Palo Alto
79%
Success rate of our group for student and fellowship grant applications (26 of 33, since we started counting
3
Research presentations done per lab member on average every year
>100
important open questions in inner ear biology

Our laboratory is located in the Edwards Building  —  We will move in early 2020 to the new Biomedical Innovations Building

Work hard , Play hard

2017 Finally to the Golden Cathedral plus more

2016 Cedar Mesa – Grand Gulch and some more canyons

2015 Coyote Buttes North – The Wave and Glamping

2014 Coyote Gulch and more

2013 Memorial Day Weekend Lab trip

Buckskin Gulch 2012 – The Trailer

Buckskin Gulch 2011 – Mud, mud, and … mud

 

Publications

Here are some recent highlights

• Ellwanger, Daniel C., Scheibinger, Mirko ., Dumont, Rachel A., Barr-Gillespie, Peter G., and Heller, Stefan. Transcriptional Dynamics of Hair-Bundle Morphogenesis Revealed with CellTrails. Cell Reports, 23(10). doi: 10.1016/j.celrep.2018.05.002 (2018). Link to the paper in Cell Reports.

The software implementation of CellTrails is a whole different piece of substantial work and is available via this link.

This paper began with a discussion between Peter and Stefan at the ARO meeting in 2014 where we wondered whether it would be feasible to determine when individual genes become actively expressed during bundle growth and maturation.  Mirko and Rachel were drawn in to identify the best time point during development when hair cells at all stages of development were present in the developing chicken utricle. Mirko profiled >1,000 cells.  Daniel took on the complex challenge of finding an unsupervised computational method to order the single cells along a trajectory that reflects hair bundle maturation and undertook a “tour-de-force” of developing a set of algorithms and their practical realization (CellTrails). The unbiased method consists of innovations and implementations that can be used for a variety of analysis steps including dimensionality reduction, clustering of single cells, determining the number of distinct clusters, as well as the computation and analysis of branching cellular trajectories, including the inference of gene expression dynamics. Moreover, CellTrails has an elegant visualization tool that is scalable and therefore compatible with datasets that contain large cell numbers. Flexible trajectory extraction and alignment of trajectories allowed us to compare the expression dynamics of the development of spatially distinct hair cell types with different hair bundle shapes. Ultimately, our study shows that it is indeed feasible to order developing vestibular hair cells based on the sequential expression of hair bundle genes alone.  Peter’s lab had a impressive toolbox of antibodies to hair bundle proteins that were essential for Mirko’s validation analyses using high resolution microscopy. We utilized the length of the hair bundle as a biological ruler to relate gene expression dynamics with hair bundle length. Our analysis revealed that control of local Ca2+ is important for hair bundle growth and moreover, it identified distinct subtypes of vestibular hair cells, which indicates that the number of hair cell subtypes in the utricle is larger than previously thought.

 

 

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Older publications

A list of all lab publications can be accessed via this link.

 

Are you ready?

Get in Touch

Lab hike 2012

Software Implementations

• CellTrails (via this link)

• Heller lab simple guide to single cell analysis (coming soon)

The Heller Lab Blog

May 21

My goal for this year is to provide more frequent updates. Congratulations to Amanda for being selected as recipient of an A.P.…

April 2018

Another year went by.  Here are some highlights. Postdoc Mirko Scheibinger got the February cover of JARO with his paper describing the…

May 2017

A sign of life!  The silence was an indication that we have been busy.  I just wanted to post here that a longer…

June 2016

  2016 has been fairly good to us thus far.  Our new NIH grant received a competitive score, which is most important…

 

Contact Us

300 Pasteur Drive, Edwards R123, Stanford University, Stanford, CA 94315, United States

+650 721 1032
hellers@stanford.edu