Research Summary
The Doetzlhofer Lab seeks to identify and characterize the gene regulatory networks that govern auditory sensory development and regeneration. The inner ear auditory sensory epithelium is critical for our ability to detect sound. Damage or loss to its mechano-sensory hair cells is permanent, leading to hearing deficits and deafness. However, in non-mammalian vertebrates, surrounding supporting cells undergo a process of de-differentiation after hair cell loss, and replace lost hair cells by either cell division or direct trans-differentiation.
Current research topics include:
- The role of RNA binding proteins LIN28B and TRIM71 in regulating auditory progenitor behavior and supporting cell plasticity.
- The function of Notch signaling pathway in supporting cell development and hair cell regeneration.
- The role of morphogen gradients in the differentiation and tonotopic specialization of the auditory organ.
Lab
Lab Website: Doetzlhofer Laboratory - Center for Sensory Biology
Selected Publications
View all on PubMed
Chrysostomou E, Zhou L, Darcy YL, Graves KA, Doetzlhofer A, Cox BC. The Notch Ligand Jagged1 Is Required for the Formation, Maintenance, and Survival of Hensen's Cells in the Mouse Cochlea. J Neurosci. 2020 Dec 2;40(49):9401-9413. doi: 10.1523/JNEUROSCI.1192-20.2020. Epub 2020 Oct 30. PMID: 33127852
Li XJ, Doetzlhofer A. LIN28B/let-7 control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling. Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22225-22236. doi: 10.1073/pnas.2000417117. Epub 2020 Aug 21. PMID: 32826333
Prajapati-DiNubila M, Benito-Gonzalez A, Golden EJ, Zhang S, Doetzlhofer A. A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea. Elife. 2019 Jun 12;8:e47613. doi: 10.7554/eLife.47613. PMID: 31187730
Campbell DP, Chrysostomou E, Doetzlhofer A. Canonical Notch signaling plays an instructive role in auditory supporting cell development. Sci Rep. 2016 Jan 20;6:19484. doi: 10.1038/srep19484. PMID: 26786414
Golden EJ, Benito-Gonzalez A, Doetzlhofer A. The RNA-binding protein LIN28B regulates developmental timing in the mammalian cochlea. Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):E3864-73. doi: 10.1073/pnas.1501077112. Epub 2015 Jul 2. PMID: 26139524
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