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Section on Human Genetics

Thomas B. Friedman, Ph.D., Chief

Research Statement

The goal of our laboratory is to identify and characterize the molecular machines and pathways necessary for the development and maintenance of the inner ear. For the past 20 years, we have contributed to the understanding of the exquisite anatomical and physiological complexity of the inner ear by identifying many of the defective genes causing deafness (“deafness genes”) in humans and by studying their biological functions in animal models. We continue to ascertain large families segregating deafness in order to identify novel deafness chromosomal loci and genes.

The five interrelated research goals of the Section on Human Genetics are:

Loci and genes for nonsyndromic deafness and Usher syndrome View larger image Loci and genes for nonsyndromic deafness and Usher syndrome.
View larger image

  1. Ascertain large families segregating deafness.
  2. Map genes for inherited forms of human syndromic and nonsyndromic deafness.
  3. Identify mutant genes associated with deafness using whole exome and genome sequencing.
  4. Engineer animal models that mimic human deafness to access pathophysiology.
  5. Reveal the pathophysiology and wild type functions of “deafness genes.”

Improved understanding of the mutated genes will provide important information on hearing and brain processing. The identification of the relevant genes will also permit early and more accurate diagnosis for certain forms of hereditary hearingand communication impairments.

Additional research information about the identification and location of the genes for nonsyndromic and syndromic hereditary hearing loss can be found on the Hereditary Hearing Loss website.

Restoration of the elongation and staircase organization of abnormally short hair cell stereocilia bundles in myosin XVa mutant mice (shaker 2) and whirlin mutant mice after gene gun mediated transfection of wild-type GFP-myosin XVa and GFP-whirlin, respectively (Belyantseva et al., 2005).

Restoration of the elongation and staircase organization of abnormally short hair cell stereocilia bundles in myosin XVa mutant mice (shaker 2) and whirlin mutant mice after gene gun mediated transfection of wild-type GFP-myosin XVa and GFP-whirlin, respectively (Belyantseva, et al., 2005).

Mouse inner hair cells labeled with antiserum against Myosin 15 (green), a molecular motor that is essential for the development and maintance of actin-based stereocilia (magenta).

(L-R, back row): Alec Callahan, Barb Zwiesler, Atteeq Rehman, Tom Friedman, Joe Duda, Jonathan Bird, Melanie Barzik.
(L-R, front row): Daniel Sutton, Rabia Faridi, Jesse Werth, Inna Belyantseva, Alexis Oguh, Liz Wilson, Elizabeth Thomason, Arik Shams.
Not pictured: Ayesha Imtiaz and Pat Riordan.

Training in the Section on Human Genetics

We are interested in hearing from motivated postdoctoral candidates with experience in genetics, protein biochemistry, molecular biology, cell biology, or related disciplines; a strong publication record; good communication skills; and enthusiasm for basic research.

Applicants should submit their curriculum vitae, a brief statement of research interests, and the names and contact information of three references.

Graduate student applicants may apply to the Graduate Partnership Program that sponsors doctoral students at the NIH through partnerships with various universities including University of Maryland, Johns Hopkins, Georgetown University, Oxford University (UK) and Cambridge University (UK).

Lab Personnel

Selected Publications

Katsuno T, Belyantseva I, Cartagena-Rivera AX, Ohta K, Crump SM, Petralia RS, Ono K, Tona R, Imtiaz A, Rehman A, Kiyonari H, Kaneko M, Wang Y-X, Abe T, Ikeya M, Fenollar-Ferrer C, Riordan GP, Wilson EA, Fitzgerald TS, Segawa K, Omori K, Ito J, Frolenkov GI, Friedman TB, Kitajiri S-I. TRIOBP-5 sculpts stereocilia rootlets and stiffens supporting cells enabling hearing. JCI Insight. 2019 June 20.

Inside the inner ear of a mouse, arc-shaped hair cell bundles emerge from the surface of the membrane. Hair cells transform incoming sound vibrations into signals that can be picked up by the auditory nerve and translated in the brain as sound.

Cover of JCI Insight, 20 June 2019. Source: Inna Belyantseva, M.D, Ph.D., NIDCD

Fang Q, Indzhykulian AA, Mustapha M, Riordan GP, Dolan DF, Friedman TB, Belyantseva IA, Frolenkov GI, Camper SA, Bird JE. The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing. eLIFE. 2015 Aug 24;4.

Cover of eLIFE: A Tale of Two Isoforms

Cover of eLIFE

Bird JE, Takagi Y, Billington N, Strub MP, Sellers JR, Friedman TB. Chaperone-enhanced purification of unconventional myosin 15, a molecular motor specialized for stereocilia protein trafficking. Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12390-5.

Rehman AU, Santos-Cortez RL, Morell RJ, Drummond MC, Ito T, Lee K, Khan AA, Basra MA, Wasif N, Ayub M, Ali RA, Raza SI, University of Washington Center for Mendelian Genomics, Nickerson DA, Shendure J, Bamshad M, Riazuddin S, Billington N, Khan SN, Friedman PL, Griffith AJ, Ahmad W, Riazuddin S, Leal SM, Friedman TB. (2014) Mutations in TBC1D24, a gene associated with epilepsy, also cause nonsyndromic deafness DFNB86. Am J Hum Genet 2014 Jan 2;94(1):144-52. doi: 10.1016/j.ajhg.2013.12.004.

Graphic representation of TBC1D24 structure (left) and its encoded protein (right). DFNB86-associated mutations are shown above the diagram, and epilepsy-associated mutations are shown below.

Riazuddin S, Belyantseva, IA, Giese APJ., Kwanghyuk L, Indzhyukulian AA, Nandamuri SP, Yousaf R, Sinha GP, Lee S, Terrell D, Hegde RS, Ali RA, Anwar S, Andre-Elizondo PB, Sirmaci A, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Ahmad W, Khan S, Akram J, Tekin M, Riazuddin Sh, Cook T, Buschbeck EK, Frolenkov G, Leal SM, Friedman TB, Ahmed ZM. (2012) Alterations of the CIB2 calcium-and integrin-binding protein cause Usher syndrome type 1J and nonsyndromic deafness DFNB4. Nature Genetics Volume 44: pages 1265-1271.

Rehman AU, Morell, RJ, Khan SY, Belyantseva IA, Boger ET, Shahzad M, Ahmed ZA, Riazuddin S, Khan SN, Friedman TB (2010) Targeted capture and next-generation sequencing identifies C9orf75, encoding TAPERIN, as the mutated gene in nonsyndromic deafness DFNB79. The American Journal of Human Genetics 86: 378-388.

Localization of TAPERIN at the base
(taper) of hair cell stereocilia in the mouse
inner ear. The American Journal of
Human Genetics

Borck G, Rehman AU, Lee K, Pogoda, H-M, Kakar N, von Ameln S, Grillet N, Hildebrand MS, Ahmed ZM, Nürnberg G, Ansar M, Basit S, Javed Q,. Morell RJ, Nasreen NA, Shearer AE, Ahmad A, Kahrizi K, Shaikh RS, RA A, Khan SN, Goebel I, Meyer NC, Kimberling WJ, Webster JA, Stephan D, Schiller M, Bahlo M, Najmabadi H, Gillespie PG, Nürnberg P, Wollnik B, Riazuddin S, Smith RJH, Ahmad W, Müller U, Hammerschmidt M, Friedman TB, Riazuddin S, Leal SM, Ahmad J, Kubisch C (2011) Loss-of-Function Mutations of ILDR1 Cause Autosomal-Recessive Hearing Impairment DFNB42. The American Journal of Human Genetics 88: 1-11.

Kitajiri S, Sakamoto T, Belyantseva IA, Goodyear RJ, Stepanyan R, Fujiwara I, Bird JE, Riazuddin S, Ahmed ZM, Hinshaw JE, Sellers J, Bartles JR, Hammer JA, Richardson GP, Griffith AJ, Frolenkov GI, Friedman TB. Actin-Bundling Protein TRIOBP Forms Resilient Rootlets of Hair Cell Stereocilia Essential for Hearing. Cell, Volume 141, Issue 5, 786-798, 28 May 2010.

Cover of Cell

Cover of Cell May 2010

Belyantseva IA, Boger ET, Naz S, Frolenkov GI, Sellers JR, Ahmed ZM, Griffith AJ, Friedman TB. Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia. Nature Cell Biology 7(2):148–56, 2005.

Nature Cell Biology cover image

Cover of Nature Cell Biology 2005

Belyantseva IA, Boger ET, Friedman TB. Myosin XVa localizes to the tips of inner ear sensory cell stereocilia and is essential for staircase formation of the hair bundle. Proceedings of the National Academy of Sciences of the USA 100:13958–63, 2003.

Last Updated Date

June 24, 2019