Brandon Cox <email@example.com>
Research Interest and Specialties
Research in the Cox lab is focused on hearing loss. Approximately 36 million Americans suffer from hearing loss, making it one of the most common disabilities in the United States (www.nidcd.nih.gov). Exposure to loud noise or certain types of drugs causes damage to specialized cells in the cochlea of the inner ear (called hair cells), which results in hearing loss. Treatments for hearing loss, such as hearing aids and cochlear implants, provide some benefit but do not restore normal hearing.
In birds, fish, amphibians, and other non-mammals, hair cells can regenerate after damage and restore hearing function. The Cox lab and others discovered that hair cell regeneration also occurs in the ears of newborn mice (Cox et al., 2014). However, when hair cells are killed at one week of age, no evidence of regeneration was detected.
The Cox lab is investigating the cell source, mechanism, and genes involved in the hair cell regeneration process that occurs in the newborn mouse ear. We are also interested the developmental changes that take place during the first weeks after birth which prevent regeneration from occurring in juvenile and adult mice. Other projects in the lab are focused on mechanisms that regulate hair cell survival during postnatal maturation, aging, regeneration, and in stressed hair cells after noise exposure. We also collaborate with Dr. Jenny Stone at the University of Washington to study the vestibular system, which regulates the sense of balance. Projects in this collaboration include hair cell turnover, hair cell regeneration, and the pathways that govern the specialization of vestibular hair cells as type I or type II.
We use mouse genetics (CreER/loxP and tetracycline inducible systems) to manipulate gene expression in specific cell types and at specific ages, as well as fate-mapping to trace the origin of regenerated hair cells. Immunostaining with confocal microscopy, as well as real time qPCR and other molecular techniques, are routinely used in the Cox lab.
Education & training
Duncan JS and Cox BC (2020) Anatomy & Development of the Inner Ear. In The Senses: A Comprehensive Reference, 2nd edition. B. Fritzsch, editor, Cambridge, Massachusetts: Elsevier Inc. Chapter 2.16
Beebe NL, Sowick CS, Kristaponyte I, Galazyuk AV, Vetter DE, Cox BC, Schofield BR (2020) Generation of a ChATCre mouse line without the early onset hearing loss typical of the C57BL/6J strain. Hearing Res 388:107896. DOI: 10.1016/j.heares.2020.107896
Hicks KL, Wisner SR, Cox BC, and Stone JS (2020) Atoh1 is required in supporting cells for regeneration of vestibular hair cells in adult mice. Hearing Res 385:107838. DOI: 10.1016/j.heares.2019.107838
Naples JG, Ruckenstein MJ, Singh J, Cox BC, and Li D (2020) Intratympanic Diltiazem-Chitosan Hydrogel as a Novel Otoprotectant against Cisplatin-Induced Ototoxicity in a Mouse Model. Otol Neurotol 41(1):115-122. DOI: 10.1097/MAO.0000000000002417
Warchol ME, Massoodnia R, Pujol R, Cox BC, and Stone JS (2019) Development of hair cell phenotype and calyx nerve terminals in the neonatal mouse utricle. J Comp Neurol 527(11): 1913-1928. DOI: 10.1002/cne.24658
Walters BJ and Cox BC (2019) Approaches for the study of epigenetic modifications in the inner ear and related tissues. Hearing Res 376:69-85. DOI: 10.1016/j.heares.2019.01.007
McGovern MM, Randle MR, Cuppini CL, Graves KA, and Cox BC (2019) Multiple supporting cell subtypes are capable of spontaneous hair cell regeneration in the neonatal mouse cochlea. Development 146(4):pii DOI: 10.1242/dev.171009
Stone JS, Wisner SR, Bucks SA, Mellado Lagarde MM, and Cox BC (2018) Characterization of adult vestibular organs in 11 CreER mouse lines. J Assoc Res Otolaryngol 19(4):381-399. DOI: 10.1007/s10162-018-0676-6
McGovern MM, Zhou L, Randle MR, and Cox BC (2018) Spontaneous hair cell regeneration is prevented by increased Notch signaling in supporting cells. Front Cell Neurosci 12:120. DOI: 10.3389/fncel.2018.00120
Cai, R, Montgomery SC, Graves KA, Caspary DM, and Cox, BC (2018) The FBN rat model of aging: investigation of ABR waveforms and ribbon synapse changes. Neurobiol Aging 62:53-63. DOI: 10.1016/j.neurobiolaging.2017.09.034
Sottile SY, Ling L, Cox BC, and Caspary DM (2017) Impact of aging on postsynaptic neuronal nicotinic neurotransmission in auditory thalamus. J Physiol 595(15):5375-5385. DOI: 10.1113/JP274467
Bucks SA, Cox BC, Vlosich BA, Manning JP, Nguyen TB and Stone JS (2017) Supporting cells remove and replace sensory receptor hair cells in a balance organ of adult mice. eLife 6:e18128 DOI: 10.7554/eLife.18128
McGovern MM, Brancheck J, Grant AC, Graves KA, and Cox BC. (2017) Quantitative analysis of supporting cell subtype labeling among CreER lines in the neonatal mouse cochlea. J Assoc Res Otolaryngol 18(2): 227-245. DOI: 10.1007/s10162-016-0598-0
Montgomery SC and Cox BC (2016) Whole mount dissection and immunofluorescence of the adult mouse cochlea. J Vis Exp 107:e53561. DOI: 10.3791/53561
Walters BJ*, Liu Z*, Crabtree M*, Coak E, Cox BC, and Zuo J. (2014) Auditory hair cell-specific deletion of p27Kip1 in postnatal mice promotes cell-autonomous generation of new hair cells and normal hearing. J Neurosci, 34:15751-15763. DOI: 10.1523/JNEUROSCI.3200-14.2014
Cox BC, Dearman JA, Brancheck J, Zindy F, Roussel MF, and Zuo J. (2014) Generation of Atoh1-rtTA transgenic mice: a tool for inducible gene expression in hair cells of the inner ear. Sci Rep 4:6885. DOI: 10.1038/srep06885
Cox BC*, Chai R*, Lenoir A, Liu Z, Zhang L, Nguyen D, Chalasani K, Steigelman KA, Fang J, Rubel EW, Cheng AG, and Zuo J. (2014) Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development 141:816-829. DOI: 10.1242/dev.103036
Mellado Lagarde, MM, Cox BC, Fang J, Taylor R, Forge A, and Zuo J. (2013) Selective ablation of pillar and Deiters’ cells severely affects cochlear postnatal development and hearing function in mice. J Neurosci 33:1564-1576. DOI: 10.1523/JNEUROSCI.3088-12.2013
Cox BC, Liu Z, Mellado Lagarde MM, and Zuo J. (2012) Conditional gene expression in the mouse inner ear using Cre-loxP. J Assoc Res Otolaryngol 13:295-322. DOI: 10.1007/s10162-012-0324-5
Liu Z, Walters BJ, Owen T, Brimble MA, Steigelman KA, Zhang L, Mellado Lagarde MM, Valentine MB, Yu Y, Cox BC, and Zuo J. (2012) Regulation of p27Kip1 by Sox2 maintains quiescence of inner pillar cells in the murine auditory sensory epithelium. J Neurosci 32:10530-10540. DOI: 10.1523/JNEUROSCI.0686-12.2012
Burns J*, Cox BC*, Thiede BR, Zuo J, and Corwin JT. (2012) In vivo proliferative regeneration of balance hair cells in newborn mice. J Neurosci 32:6570-6577. DOI: 10.1523/JNEUROSCI.6274-11.2012
Liu Z, Dearman JA, Cox BC, Walters BJ, Zhang L, Ayrault O, Zindy F, Gan L, Roussel M, and Zuo J. (2012) Age-dependent in vivo conversion of mouse cochlear pillar and Dieters’ cells to immature hair cells by Atoh1 ectopic expression. J Neurosci 32: 6600-6610. DOI: 10.1523/JNEUROSCI.0818-12.2012
Yu Y, Weber T, Yamashita Y, Liu Z, Valentine MB, Cox BC, and Zuo J. (2010) In vivo proliferation of postmitotic cochlear supporting cells by acute ablation of the retinoblastoma protein in neonatal mice. J Neurosci 30: 5927-5936. DOI: 10.1523/JNEUROSCI.5989-09.2010
Note * denotes that authors contributed equally
R01 DC014441 -- Mechanisms that regulate hair cell survival NIH/National Institute on Deafness and other Communicative Disorders 6/1/2016 – 5/31/2021
R01 DC013771 with Dr. Stone - Fate acquisition and function of type I and II vestibular hair cells in mammals NIH/National Institute on Deafness and other Communicative Disorders 4/1/2019 - 3/31/2024