Research Area Affiliations
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.
Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c. Pan B, Askew C, Galvin A, Heman-Ackah S, Asai Y, Indzhykulian AA, Jodelka FM, Hastings ML, Lentz JJ, Vandenberghe LH, Holt JR, Géléoc GS. Nat Biotechnol. 2017 Mar;35(3):264–272.
Rescue of hearing by gene delivery to inner-ear hair cells using exosome-associated AAV. György B, Sage C, Indzhykulian AA, Scheffer DI, Brisson AR, Tan S, Wu X, Volak A, Mu D, Tamvakologos PI, Li Y, Fitzpatrick Z, Ericsson M, Breakefield XO, Corey DP, Maguire CA. Mol Ther. 2017 Feb 1;25(2):379–391.
Primary cilia are not calcium-responsive mechanosensors. Delling M*, Indzhykulian AA*, Liu X, Li Y, Xie T, Corey DP, Clapham DE. Nature. 2016 Mar 31;531(7596):656–60.
The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. Fang Q, Indzhykulian AA, Mustapha M, Riordan GP, Dolan DF, Friedman TB, Belyantseva IA, Frolenkov GI, Camper SA, Bird JE. Elife. 2015 Aug 24;4.
Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells. Indzhykulian AA, Stepanyan R, Nelina A, Spinelli KJ, Ahmed ZM, Belyantseva IA, Friedman TB, Gillespie PG, Frolenkov GI. PLoS Biol, Jun, 11(6).
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