Teresa Nicolson, Ph.D.

nicolson@ohsu.edu

Associate Professor, Oregon Hearing Research Center

Investigator, Howard Hughes Medical Institute

Primary Affiliation

SOM-Otolaryngology & Head & Neck Surgery Department

Program Affiliation

Neuroscience Graduate Program

Program in Molecular & Cellular Biosciences

Background

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 with a joint appointment in the Vollum Institute. In 2005, she was promoted to associate professor and became a Howard Hughes Investigator.

Summary of Current Research

The Nicolson lab studies the molecular basis of hearing and balance in zebrafish. In the inner ear or lateral line of the fish, sensory hair cells transduce mechanical energy into electrical signals. Depolarization leads to graded release of neurotransmitter at the basal end of hair cells. The lab is focused on identifying genes required for function of the transduction apparatus in the hair bundle and neurotransmission at the specialized ribbon synapses.

Past large-scale screens of over 7000 genomes have yielded two dozen genes that are specific to auditory/vestibular function in zebrafish larvae. Several of the genes including myosin VIIa, cadherin 23, and protocadherin 15a are important for hair-bundle integrity and function. Cadherin 23 and Protocadherin 15 are particularly interesting as weak alleles leave zebrafish hair bundles intact, yet receptor potentials are affected. Collective evidence presented by the Nicolson lab and other labs suggests that these novel cadherins form the extracellular filaments that mechanically gate transduction channels in hair cells.

Ongoing efforts of the Nicolson lab are largely directed at cloning the genes identified from the forward genetic screens and understanding the function of the proteins. In addition, new ways of analyzing the collection of auditory/vestibular mutants are being developed such as measuring the vestibulo-ocular reflex, and recording currents in post-synaptic neurons to assess synaptic transmission. Efforts are also directed at creating transgenic lines driving hair-cell specific expression of tagged proteins or calcium indicators for live imaging experiments.

By exploring the mutant phenotypes at the behavioral, cellular and electrophysiological level, we aim to gain a better understanding of the basic molecular mechanisms involved in transduction and transmission in hair cells, and to apply our findings to understanding the pathology of congenital deafness in humans.

Selected Publications

Trapani, J.G., Obholzer, N., Mo, W., Brockerhoff, S.E., and Nicolson, T. (2009) Synaptojanin1 is required for temporal fidelity of synaptic transmission in hair cells. PLoS Genet. 5:e1000480.

Obholzer, N., Wolfson, S., Trapani, J.G., Mo, W., Nechiporuk, A., Busch-Nentwich, E., Seiler, C., Sidi, S., Söllner, C., Duncan, R.N., Boehland, A., and Nicolson, T. (2008) Vesicular glutamate transporter 3 is required for synaptic transmission in zebrafish hair cells. J. Neurosci. 28:2110-2118.

Seiler, C., Finger-Baier, K.C., Rinner, O., Makhankov, Y.V., Schwarz, H., Neuhauss, S.C., and Nicolson, T. (2005) Duplicated genes with split functions: independent roles of protocadherin 15 orthologues in zebrafish hearing and vision. Development 132:615-623.