A deeper understanding of hearing loss and vestibular deficits is invaluable for treating deafness and imbalance

Research

Research Goals

The goals of the Nicolson lab are to understand the molecular basis of the senses of hearing and balance.

The majority of genes that we have identified in behavioral screens for auditory/vestibular deficits are implicated in human hearing loss.

Picture: Right panel, scanning electron micrograph of a sensory hair cell in a zebrafish larva. Left panel, schematic of a sensory hair cell and supporting cells.

Hair cell genes
MECHANOTRANSDUCTION:
cdh23, ush1c, pcdh15a, myo7aa, myo6b, lhfpl5a, tmie, ap1p1, tomt

SYNAPTIC TRANSMISSION:
cav1.3a, vglut3, synj1, rbc3a, nsf
nav1.6a

TRANSDUCTION: cdh23, ush1c, pcdh15a, myo7aa, myo6b, lhfpl5a, tmie, ap1p1, tomt
TRANSMISSION: cav1.3a, vglut3, synj1, rbc3a, nsf
nav1.6a

Research Goals

The goals of the Nicolson lab are to understand the molecular basis of the senses of hearing and balance.

The majority of genes that we have identified in behavioral screens for auditory/vestibular deficits are implicated in human hearing loss.

Annotated photographs of Sensory hair cells of the inner ear and lateral line organ in larvae (k, kinocilium; hb, hair bundle; hc, hair cell body; sc, supporting cell; 5 dpf, 5 days postfertilization)

Research Methods

We use zebrafish to explore the basic biology of the auditory/vestibular system in vertebrates and to provide animal models of human hearing loss.

Our methods include:

  • forward and reverse genetics
  • live-cell imaging of whole animals, and
  • cellular and behavioral analyses
Micrograph of Using transgenic fish to image dopaminergic efferents (green) innervating a neuromast (hair cells in magenta).
Chart of a Rotation of the fish excites the utricle of the inner ear leading to reflexive eye movements

Picture on the left: Sensory hair cells of the inner ear and lateral line organ in larvae (k, kinocilium; hb, hair bundle; hc, hair cell body; sc, supporting cell; 5 dpf, 5 days postfertilization)

Pictures above: 1.Using transgenic fish to image dopaminergic efferents (green) innervating a neuromast (hair cells in magenta); 2. Rotation of the fish excites the utricle of the inner ear leading to reflexive eye movements

Videos on the left: Upper video, spontaneous swimming bouts in mutant larvae. Note the circling behavior of the myo7a mutants. Mutations in myo7a cause deafness and impaired balance in fish, mice and humans. Lower video, quantification of the vestibulospinal reflex in larvae using ZebraZoom software.

Annotated photographs of Sensory hair cells of the inner ear and lateral line organ in larvae (k, kinocilium; hb, hair bundle; hc, hair cell body; sc, supporting cell; 5 dpf, 5 days postfertilization)

Research Methods

We use zebrafish to explore the basic biology of the auditory/vestibular system in vertebrates and to provide animal models of human hearing loss.

Our methods include:

  • forward and reverse genetics
  • imaging of whole animals, and
  • cellular and behavioral analyses
Micrograph of Using transgenic fish to image dopaminergic efferents (green) innervating a neuromast (hair cells in magenta).
Chart of a Rotation of the fish excites the utricle of the inner ear leading to reflexive eye movements

Pictures above: 1. Sensory hair cells of the inner ear and lateral line organ in larvae (k, kinocilium; hb, hair bundle; hc, hair cell body; sc, supporting cell; 5 dpf, 5 days postfertilization); 2. Using transgenic fish to image dopaminergic efferents (green) innervating a neuromast (hair cells in magenta); 3. Rotation of the fish excites the utricle of the inner ear leading to reflexive eye movements

Videos on the left: Upper video, spontaneous swimming bouts in mutant larvae. Note the circling behavior of the myo7a mutants. Mutations in myo7a cause deafness and impaired balance in fish, mice and humans. Lower video, quantification of the vestibulospinal reflex in larvae using ZebraZoom software.

Micrograph of Hair bundles of stereocilia (Actin-RFP in red) and individual kinocilia (Tubulin-YFP in yellow) in the inner ear of a live, undissected double transgenic larva 

Mechanotransduction in hair cells

We are interested in how hair cells transduce mechanical stimuli into electrical signals. To date, we have identified more than nine genes that are specifically required for mechanotransduction, including components of the transduction machinery. Our goal is to understand the precise role of these components in this fascinating process.

Micrograph of a Cluster of lateral line hair cells labeled with anti-Tubulin (teal) and anti-Vglut3 (yellow) antibodies

Synaptic transmission in hair cells

Hair cells communicate to neurons using ribbon synapses. How this communication is achieved at the molecular level and how these synapses develop are some fundamental questions that we are addressing using a wide range of methods.

Micrograph of Axonal projections in a 5 day-old larva labeled with anti-Tubulin antibodies (magenta; DAPI labeling of cell bodies shown in blue).

Beyond the first synapse

We have begun to characterize a rarer class of mutants that have defects that are downstream of hair cells and appear to affect more central processing of auditory and vestibular stimuli.

Stay tuned! 

Meet Our Team

Teresa Nicolson, PI, Headshot

Teresa Nicolson

After receiving her B.S. in Biochemistry at Western Washington University, Teresa Nicolson received her Ph.D. in Biological Chemistry in 1995 from the University of California, Los Angeles. She then trained as a post-doctoral fellow at the Max Planck Institute for Developmental Biology in Tuebingen, Germany. In 1999, Teresa became an independent Group Leader at the same institute. In 2003, she was appointed as an assistant professor to the Oregon Hearing Research Center (OHRC) at OHSU with a joint appointment in the Vollum Institute. She was promoted to associate professor in 2005 and professor in 2014. Teresa was an HHMI Investigator from 2005 to 2013. In 2019 she then joined the Research Division of Otolaryngology – Head & Neck Surgery as a professor at Stanford University.

Stanford Profile
Anna Shipman Headshot

Anna Shipman

Postdoctoral Fellow

Anna received her Ph.D. in Molecular Biology and Biochemistry at the University of Missouri-Kansas City. Anna’s thesis focused on regulation of cell growth and proliferation in Drosophila. Anna is currently studying central auditory/vestibular deficits in the raumschiff mutant.

Eliot Smith Headshot

Eliot Smith

Postdoctoral Fellow

Eliot studied biochemical aspects of enzyme function for his Ph.D. in Biochemistry and Cellular/Molecular Biology at theUniversity of Tennessee. Eliot also worked as a postdoctoral fellow on the function of Ndr kinases in the zebrafish retina before joining the lab. Eliot is currently characterizing the role of the Tmc1/2 proteins in inner ear hair cells.

Matthew Esqueda Headshot

Matthew Esqueda

Research Technician

Matthew earned a B.S. in Biology at the University of Oregon. As an undergraduate Matthew worked with zebrafish in the Washbourne lab at the Institute of Neuroscience.

Yan Gao Headshot

Yan Gao

Postdoctoral Fellow

Yan received her Ph.D. in Biology at Nanjing University. Yan characterized Krueppel-mediated embryonic patterning in Xenopus. Yan is currently studying central auditory/vestibular deficits in the starliner mutant.

Contact Us

Teresa Nicolson, PI

Lab Location

300 Pasteur Drive
Edwards R139
Stanford University
Stanford, CA 94305
United States

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Lab Alumni

  • Christian Söllner, Medical Science Liaison, GlaxoKlineSmith, Germany
  • Christoph Seiler, Director Zebrafish Core, Children’s Hospital of Philadelphia
  • Elisabeth Busch-Nentwich, Associate Principal Investigator, University of Cambridge, UK
  • Samuel Sidi, Associate Professor, Mount Sinai Icahn School of Medicine
  • Bettina Schmid, Senior Scientist, Ludwig Maximilian University, Germany
  • Qianyung Liu, Principal Scientist, Astellas Pharma Global Development
  • Nikolaus Obholzer, Associate Director of Bioinformatics, Kronos Bio
  • Joseph Trapani, Associate Professor, University of Amherst
  • Greta Glover, Instrumentation Biologist, Reed College
  • Katie Kindt, ChiefSection on Sensory Cell Development and Function, NIDCD
  • Lavinia Sheets, Assistant Professor, Washington University
  • Weike Mo, Vice President of Science, Genabio Diagnostics
  • Zev Einhorn, Associate Director Hematology Customer and Market Insights, Value Access & Payments, Bristol Myers Squibb
  • Rachel Clemens, Business Development Manager, Axiom Space
  • Cecilia Toro-Philips, Assistant Professor, Sarah Lawrence College
  • Reo Maeda, Group leader, Ricoh Company, Japan
  • Timothy Erickson, Assistant Professor, University of New Brunswick, Canada
  • Itallia Pacentine, National Library of Medicine postdoctoral fellow in Biomedical Informatics, OHSU
Zebrafish Swimming Time Sequence

Selected publications

2020

Gao, Yan, and Teresa Nicolson. “Temporal Vestibular Deficits in Synaptojanin 1 (Synj1) Mutants.” Frontiers in Molecular Neuroscience 13 (2020): 604189. https://doi.org/10.3389/fnmol.2020.604189.

Smith, Eliot T., Itallia Pacentine, Anna Shipman, Matthew Hill, and Teresa Nicolson. “Disruption of Tmc1/2a/2b Genes in Zebrafish Reveals Subunit Requirements in Subtypes of Inner Ear Hair Cells.” The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 40, no. 23 (June 3, 2020): 4457–68. https://doi.org/10.1523/JNEUROSCI.0163-20.2020.

2019

Pacentine, Itallia V., and Teresa Nicolson. “Subunits of the Mechano-Electrical Transduction Channel, Tmc1/2b, Require Tmie to Localize in Zebrafish Sensory Hair Cells.” PLoS Genetics 15, no. 2 (February 2019): e1007635. https://doi.org/10.1371/journal.pgen.1007635.

2017

Erickson, Timothy, Clive P. Morgan, Jennifer Olt, Katherine Hardy, Elisabeth Busch-Nentwich, Reo Maeda, Rachel Clemens, et al. “Integration of Tmc1/2 into the Mechanotransduction Complex in Zebrafish Hair Cells Is Regulated by Transmembrane O-Methyltransferase (Tomt).” ELife 6 (May 23, 2017). https://doi.org/10.7554/eLife.28474.

Maeda, Reo, Itallia V. Pacentine, Timothy Erickson, and Teresa Nicolson. “Functional Analysis of the Transmembrane and Cytoplasmic Domains of Pcdh15a in Zebrafish Hair Cells.” The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 37, no. 12 (March 22, 2017): 3231–45. https://doi.org/10.1523/JNEUROSCI.2216-16.2017.

2014

Maeda, Reo, Katie S. Kindt, Weike Mo, Clive P. Morgan, Timothy Erickson, Hongyu Zhao, Rachel Clemens-Grisham, Peter G. Barr-Gillespie, and Teresa Nicolson. “Tip-Link Protein Protocadherin 15 Interacts with Transmembrane Channel-like Proteins TMC1 and TMC2.” Proceedings of the National Academy of Sciences of the United States of America 111, no. 35 (September 2, 2014): 12907–12. https://doi.org/10.1073/pnas.1402152111.

All Publications on PubMed

Pictures in the main collage (above) from left to right

Row 1

  1. Electron micrograph of a cross section of an inner ear hair bundle
  2. Vital dye labeling of mechanically sensitive hair cells in a transmembrane channel like (tmc) double mutant fish
  3. Scanning electron micrograph of a cluster of sensory hair cells at the surface of the skin used for detecting water flow

Row 2

  1. Molecular analysis reveals two hair cell types in the inner ear resembling Type I and II hair cells (image of  Actin-GFP and FM4-64 in magenta in a tmc double mutant) 
  2. Side view of the transparent inner ear of a live zebrafish larva (otoliths overlaying hair cells of the utricle and saccule are visible)
  3. Vital dye labeling (magenta) of a rosette of lateral line hair cells (‘neuromasts’) in a GFP transgenic fish