Education & Training
- Postdoctoral Fellow, Neuroscience, Johns Hopkins University and The Scripps Research Institute, 2021
- Ph.D., Neuroscience, University of California, Davis, 2013
- B.S., Biology, Brigham Young University, Idaho, 2008
Research Interest Summary
Proteostasis in the Auditory System
Proteostasis involves the proper synthesis, assembly, trafficking and localization of proteins within the auditory system. Many unique and highly specialized proteins with exquisitely precise subcellular localizations are critical for each step of sound processing. Many forms of hearing loss involve improper assembly, trafficking, and/or regulation of key auditory proteins.
We want to know how critical auditory proteins are assembled, trafficked and properly localized, and how these processes are affected in hearing loss.
We employ a multifaceted experimental toolkit that includes mouse genetics, biochemistry, fluorescent and electron microscopy and cell and tissue culture to investigate our research questions.
Genetics of Hearing Loss and Deafness
Hearing loss is the most common sensory deficit. There are over 100 different gene mutations that lead to hearing loss and deafness. Many of these are in genes with undetermined functions.
What are the functions of each of these deafness-linked genes in auditory processing, and how do mutations affect their function?
We make mouse mutants of deafness-associated genes using CRISPR/CAS9 and then study the structure and function of the auditory system under normal and mutant conditions. This strategy has led to the discovery of a wealth of information about normal auditory function and has the potential to uncover novel therapeutic targets for hearing loss.
Development of New Therapies for Hearing Loss
Hearing loss is the most common sensory deficit, affecting both the young and old. Cochlear implants and hearing aids have provided improvements for many people, but they do not perfectly replicate normal hearing, and have a wide range of outcomes. Unfortunately they are not useful for a significant number of patients for a variety of reasons. Thus there is a significant need for novel therapeutic options for the numerous people affected by hearing loss.
How can we effectively deliver useful therapies to hair cells in the inner ear? Can we develop relevant biological, pharmaceutical or genetically-based therapies that can restore normal function of the auditory system rather than by artificially replacing or augmenting function (as with cochlear implants or hearing aids)?
X Liang*, X Qiu*, G Dionne*, Christopher L. Cunningham, ML Pucak, G Peng, Y Kim, A Lauer, L Shapiro, U Müller. 2021. Cib2 and Cib3 are auxiliary subunits of the mechanotransduction channel of hair cells. Neuron. Jun 4. DOI: 10.1016/j.neuron.2021.05.007. *These authors contributed equally to this work.
Christopher L. Cunningham*, X Qiu*, Z Wu, B Zhao, G Peng, Y Kim, A Lauer, U Müller. 2020. TMIE defines pore and gating properties of the mechanotransduction channel of mammalian cochlear hair cells. Neuron. Apr 16. doi: 10.1016/j.neuron.2020.03.033. *These authors contributed equally to this work.
Christopher L. Cunningham*, Ulrich Müller*. 2019. Molecular structure of the hair cell mechanoelectrical transduction complex. CSHL Perspectives in Medicine. 2019 May 1;9(5). pii: a033167. doi: 10.1101/cshperspect.a033167. *Co-corresponding authors.
Christopher L. Cunningham, Z Wu, A Jafari, B Zhao, K Schrode, S Harkins-Perry, A Lauer, U Müller. 2017. The Murine Catecholamine Methyltransferase mTOMT is Essential for Mechanotransduction by Cochlear Hair Cells. eLife. May 15; 6. doi: 10.7554/eLife.24318.
Z Wu, N Grillet, B Zhao, Christopher Cunningham, S Harkins-Perry, B Coste, S Ranade, N Zebarjadi, M Beurg, R Fettiplace, A Patapoutian, U Müller. 2016. Mechanosensory hair cells express two molecularly distinct mechanotransduction channels. Nature Neuroscience. Nov 28. doi:10.1038/nn.4449.
C Gil-Sanz, A Espinosa, SP Fregoso, KK Bluske, Christopher L. Cunningham, I Martinez-Garay, SJ Franco, U Müller. 2015. Lineage tracing using Cux2-Cre and Cux2Cre-ERT2 mice. Neuron. 86(4):1091-9.
Christopher L. Cunningham, V Martinez-Cerdeno, SC Noctor. 2013. Microglia regulate the number of precursor cells in the developing cerebral cortex. Journal of Neuroscience. Mar 6;33(10):4216-33. doi: 10.1523/JNEUROSCI.3441-12.2013.