About My Research
Dr. Artur Indzhykulian’s research focuses on hair cells, which are the sensory cells of the inner ear. Hair cells detect sub-nanometer vibrations, induced by sounds or acceleration forces, with a bundle of precisely organized ‘hairs,’ called stereocilia. Often inherited deafness or vestibular impairment is caused by malfunction of a protein, important for bundle’s function, resulting in abnormalities of bundle morphology and/or function.
The Indzhykulian Lab studies the role of proteins that form and maintain stereocilia to better understand their place in bundle’s integrity and maintenance. Several such proteins, critical for stereocilia function, form the hair cell mechanotransduction complex, which converts sound to an electrical signal our brain can understand. Malfunction of many of these proteins causes Usher syndrome, a devastating disease that affects both hearing and vision.
His laboratory uses state-of-the-art electrophysiology, optical microscopy, and electron microscopy techniques to better understand the function of the individual proteins within the complex and to develop new gene therapy methods to treat Usher syndrome in both the ear and eye.
- PKHD1L1 is required for stereocilia bundle maintenance, durable hearing function and resilience to noise exposure. bioRxiv. 2024 Mar 27.
- PKHD1L1, a gene involved in the stereocilia coat, causes autosomal recessive nonsyndromic hearing loss. Hum Genet. 2024 Mar 09.
- PKHD1L1, A Gene Involved in the Stereocilia Coat, Causes Autosomal Recessive Nonsyndromic Hearing Loss. medRxiv. 2023 Dec 19.
- Large-scale annotated dataset for cochlear hair cell detection and classification. bioRxiv. 2023 Sep 01.
- Rescue of hearing by adenine base editing in a humanized mouse model of Usher syndrome type 1F. Mol Ther. 2023 08 02; 31(8):2439-2453.
- SKOOTS: Skeleton oriented object segmentation for mitochondria. bioRxiv. 2023 May 08.
- Mini-PCDH15 gene therapy rescues hearing in a mouse model of Usher syndrome type 1F. Nat Commun. 2023 04 26; 14(1):2400.
- Reprogramming by drug-like molecules leads to regeneration of cochlear hair cell-like cells in adult mice. Proc Natl Acad Sci U S A. 2023 04 25; 120(17):e2215253120.
- The hair cell analysis toolbox is a precise and fully automated pipeline for whole cochlea hair cell quantification. PLoS Biol. 2023 03; 21(3):e3002041.
- Electron Microscopy Techniques for Investigating Structure and Composition of Hair-Cell Stereociliary Bundles. Front Cell Dev Biol. 2021; 9:744248.
- Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish. Elife. 2021 10 19; 10.
- Norrie disease protein is essential for cochlear hair cell maturation. Proc Natl Acad Sci U S A. 2021 09 28; 118(39).
- Serial scanning electron microscopy of anti-PKHD1L1 immuno-gold labeled mouse hair cell stereocilia bundles. Sci Data. 2020 06 17; 7(1):182.
- Renewed proliferation in adult mouse cochlea and regeneration of hair cells. Nat Commun. 2019 12 04; 10(1):5530.
- PKHD1L1 is a coat protein of hair-cell stereocilia and is required for normal hearing. Nat Commun. 2019 08 23; 10(1):3801.
- Gene Transfer with AAV9-PHP.B Rescues Hearing in a Mouse Model of Usher Syndrome 3A and Transduces Hair Cells in a Non-human Primate. Mol Ther Methods Clin Dev. 2019 Jun 14; 13:1-13.
- Mechanotransduction current is essential for stability of the transducing stereocilia in mammalian auditory hair cells. Elife. 2017 03 28; 6.
- Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. Nat Biotechnol. 2017 03; 35(3):264-272.
- Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV. Mol Ther. 2017 02 01; 25(2):379-391.
- Tryptophan-rich basic protein (WRB) mediates insertion of the tail-anchored protein otoferlin and is required for hair cell exocytosis and hearing. EMBO J. 2016 12 01; 35(23):2536-2552.
- Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice. PLoS One. 2016; 11(5):e0155577.
- Primary cilia are not calcium-responsive mechanosensors. Nature. 2016 Mar 31; 531(7596):656-60.
- In the Right Place at the Right Time: Is TMC1/2 the Transduction Channel for Hearing? Cell Rep. 2015 Sep 08; 12(10):1531-2.
- The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. Elife. 2015 Aug 24; 4.
- XIRP2, an actin-binding protein essential for inner ear hair-cell stereocilia. Cell Rep. 2015 Mar 24; 10(11):1811-8.
- Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells. PLoS Biol. 2013; 11(6):e1001583.
- Alterations of the CIB2 calcium- and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nat Genet. 2012 Nov; 44(11):1265-71.
- TRPA1-mediated accumulation of aminoglycosides in mouse cochlear outer hair cells. J Assoc Res Otolaryngol. 2011 Dec; 12(6):729-40.
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