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: Genes identified by the lab that are required for mechanotransduction and synaptic transmission in zebrafish hair cells
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.
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
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
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
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.
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.
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
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.
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
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
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
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.
Simon Wu
Research Scientist
Simon studied gene regulatory networks required for regulation of epithelial-mesenchymal transitions in zebrafish for his Ph.D. thesis in Developmental & Stem Cell Biology at Duke University. Before joining the lab, Simon worked as a postdoctoral fellow on chemokine signaling during embryogenesis and the development of brain asymmetry in zebrafish. Simon is currently characterizing a potential new member of the mechanotransduction complex in sensory hair cells.
Contact Us
Teresa Nicolson, PI
650-725-3708
Lab Location
300 Pasteur Drive
Edwards R139
Stanford University
Stanford, CA 94305
United States
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Selected publications
Pacentine, I.V. and Nicolson, T. (2019) Subunits of the mechano-electrical transduction channel, Tmc1/2b, require Tmie to localize in zebrafish hair cells. PLoS Genetics6;15(2):e1007635. PMID: 30726219
Erickson, T., Morgan, C., Olt, J., Hardy, K., Busch-Nentwich, E., Maeda, R., Clemens-Grisham, R., Krey, J., Nechiporuk, A., Barr-Gillespie, P., Marcotti, W., and Nicolson, T.(2017) Integration of Tmc1/2 into the mechanotransduction complex is regulated by Transmembrane O-methyltransferase in hair cells. eLife 6:e28474. PMID: 28534737
Maeda R., Pacentine I.V., Erickson T., Nicolson T. (2017) Functional analysis of the transmembrane and cytoplasmic domains of Pcdh15a in zebrafish hair cells. Journal of Neuroscience 37:3231-3245. PMID: 28219986
Maeda, R., Kindt, K. S., Mo, M., Morgan, C. P., Erickson, T., Zhao, H., Clemens-Grisham, R., Barr-Gillespie, P.G., and Nicolson, T. (2014) Tip-link protein protocadherin 15 interacts with transmembrane channel-like proteins TMC1 and TMC2. Proc. Natl. Acad. Sci., 111 (35): 12907-12912. PMID: 25114259
Pictures in the main collage (above) from left to right
Row 1
- Electron micrograph of a cross section of an inner ear hair bundle
- Vital dye labeling of mechanically sensitive hair cells in a transmembrane channel like (tmc) double mutant fish
- Scanning electron micrograph of a cluster of sensory hair cells at the surface of the skin used for detecting water flow
Row 2
- Side view of the transparent inner ear of a live zebrafish larva (otoliths overlaying hair cells of the utricle and saccule are visible)
- Vital dye labeling (magenta) of a rosette of lateral line hair cells (‘neuromasts’) in a GFP transgenic fish