Stepanyan Lab

Kumar Alagramam, PhD

Ruben Stepanyan, Ph.D.


Assistant Professor
Email: rxs690@case.edu
Phone: 216.844.3690

The goal of Ruben Stepanyan's lab The goal of the lab’s research is to study hair cell mechanosensitivity and calcium homeostasis in normal and pathological conditions.  Mechanosensitivity of hair cells is necessary for our hearing while calcium is an essential modulator of mechano-electrical transduction. 

During excessively loud sounds and noise a substantial amount of calcium ions enter hair cells through mechanotransduction channels.  Therefore it is important for hair cells to be able to buffer and extrude excessive Ca2; compromised calcium balance is a significant factor leading to hair cell death. 

Outer hair cells, one of the two types of auditory hair cell in mammalian cochlea, rely on mobile calcium buffers and plasma membrane calcium pumps to regulate calcium levels.  A particular interest of the lab is establishing the exact mechanism by which sounds and noise lead to calcium overload in basal, high frequency, outer hair cells.  Generally, hearing loss occurs at the higher frequencies first, and it is basal outer hair cells, which are the most vulnerable to a variety of insults, including loud noise and ototoxic drugs.  The following methods will be commonly utilized in the lab – patch-clamp, fluorescent imaging, electron microscopy, and audiology techniques.

 

SELECTED PUBLICATIONS

Indzhykulian AA, Stераnyаn R, Nelina A, Spinelli KJ, Ahmed ZM, Belyantseva IA, Friedman TB, Gillespie PG, Frolenkov GI.  Molecular remodeling of tip links underlies mechanosensory regeneration in auditory hair cells.  PLOS Biology. 2013. 11(6):e1001583.

Szarama KB, Stepanyan R, Petralia RS, Gavara N, Frolenkov GI, Kelley MW, Chadwick RS.  Fibroblast Growth Factor Receptor 3 regulates microtubule formation and cell surface mechanical properties in the developing organ of Corti.  BioArchitecture.  2012. 2(6):214-9.

Stераnyаn R, Indzhykulian AA, Vélez-Ortega AC, Boger ET, Steyger PS, Friedman TB, Frolenkov GI.  TRPA1-mediated accumulation of aminoglycosides in mouse cochlear outer hair cells.  J Assoc Res Otolaryngol.  2011. 12(6):729-40.

Kitajiri S, Sakamoto T, Belyantseva IA, Goodyear RJ, Stераnyаn R, Fujiwara I, Bird JE, Riazuddin S, Riazuddin S, Ahmed ZM, Hinshaw JE, Sellers J, Bartles JR, Hammer JA 3rd, Richardson GP, Griffith AJ, Frolenkov GI, Friedman TB.  Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing.  Cell.  2010.  141(5):786-98.

Belyantseva IA, Perrin BJ, Snnemann K, Zhu M, Stераnyаn R, McGee JA, Frolenkov GI, Walsh E, Friderici KH, Friedman TB, Ervasti JM.  Gamma-actin is required for cytoskeletal maintenance but not development.  Proc Natl Acad Sci U S A.  2009.  106(24):9703-8.

Stераnyаn R, Frolenkov GI.  Fast adaptation and Ca2+-sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells.  Journal of Neuroscience.  2009.  29(13):4023-34.

Novak P, Li C, Shevchuk AI, Stераnyаn R, Caldwell M, Hughes S, Smart TG, Gorelik J, Ostanin VP, Lab MJ, Moss GW, Frolenkov GI, Klenerman D, Korchev YE. Nanoscale live-cell imaging using hopping probe ion conductance microscopy.  Nature Methods.  2009.  6(4):279-81.

Stераnyаn R, Belyantseva IA, Griffith AJ, Friedman TB, Frolenkov GI.  Auditory mechanotransduction in the absence of functional myosin-XVa.  Journal of Physiology (London).  2006.  576(3):801-8.