Physiology

GREGORY I. FROLENKOV, Ph.D. Associate Professor Ph.D. Moscow Institute of Physics and Technology & Cardiology Research Center, 1988 Office: MS-615 Medical Center 0298 Tel: (859) 323-8729 Lab: MS-617, Tel: 323-8730 E-mail: gregory.frolenkov@uky.edu

Cellular and molecular mechanisms of hearing

Most cases of severe hearing loss and deafness are associated with damage to the inner ear hair cells. These mechanosensory cells are crucial for our senses of hearing and balance. In addition to mechanoreception, some hair cells can contract and elongate when their intracellular potential is changed. This unique type of cellular motility amplifies sound-induced vibrations in the inner ear and determines the extraordinary sensitivity of mammalian hearing. Our laboratory studies both mechanosensation and active motility in hair cells. We use mouse models with targeted gene deletion (knockout) or deafness-related mutations to determine the function of specific proteins. The function is assessed at the whole animal, cellular, and molecular levels. Patch-clamp, calcium imaging, live cell confocal microscopy, scanning electron microscopy, and audiology techniques are widely used. We also develop emerging nanotechniques to visualize individual proteins at the surface of a living cell and to probe their function. Prospective post-doctoral fellows and graduate students are expected to learn cell physiology and cell biology techniques at the cutting edge level and collaborate with the number of laboratories, including groups at NIDCD/NIH, Harvard University, Imperial College (United Kingdom), Cambridge University (United Kingdom), University of Michigan, and Northwestern University.

Lab personnel

• Stephanie Edelmann, MS, Pr. Scientist II, seedelm@uky.edu
• Artur Indzhykulian, MD, PhD, Post-Doctoral Fellow, ain222@uky.edu
• Anastasiia Nelina, MD, Temp. Technician, ane227@uky.edu
• Ghanshyam Sinha, PhD, Post-Doctoral Fellow, ghanshyam.sinha@uky.edu
• Ruben Stepanyan, PhD, Research Associate, rstep2@uky.edu
• Alejandra Catalina Velez-Ortega, MS, Graduate Student, catavelezo@uky.edu

Recent publications:

Kitajiri S, Sakamoto T, Belyantseva IA, Goodyear RJ, Stepanyan 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. (2010) Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing. Cell 141: 786-798 (featured on the cover).

Stepanyan R, Frolenkov GI. (2009) Fast adaptation and Ca2+-sensitivity of the mechanotransducer require myosin-XVa in inner but not outer cochlear hair cells. J. Neurosci. 29: 4023-4034.

Novak P, Li C, Shevchuk AI, Stepanyan R, Caldwell M, Hughes S, Smart TG, Gorelik J, Ostanin VP, Lab MJ, Moss GWJ, Frolenkov GI (co-corresponding author), Klenerman D, Korchev YE. (2009) Hopping probe ion conductance microscopy allows nanoscale imaging of live complex cellular structures. Nat. Methods 6: 279-281 (featured on the cover)

Stepanyan R, Belyantseva IA, Griffith AJ, Friedman TB, Frolenkov GI. (2006) Auditory mechanotransduction in the absence of functional myosin-XVa. J. Physiol. (London) 576.3: 801-808.

Frolenkov GI. (2006) Regulation of electromotility in the cochlear outer hair cell. J. Physiol. (London) 576.1: 43-48 (featured on the cover).

Belyantseva IA, Boger ET, Naz S, Frolenkov GI, Ahmed ZM, Sellers J, Griffith AJ, Friedman TB. (2005) Programmed elongation of inner ear hair cell stereocilia requires interaction of myosin XVa and whirlin. Nat. Cell Biol. 7: 148-156 (featured on the cover).

Frolenkov GI, Belyantseva IA, Friedman TB, Griffith AJ. (2004) Genetic insights into the morphogenesis of inner ear hair cells. Nat. Rev. Genet. 5: 489-498 (featured on the cover).

Research Funding

R01 DC008861; NIDCD/NIH
R01 DC009434; NIDCD/NIH
G40; The Royal National Institute for Deaf People (United Kingdom)
Deafness Research Foundation
National Organization for Hearing Research Foundation
Kentucky Science and Engineering Foundation

Other Publications