Prof. Avraham Karen

Affiliation:Sackler School of Medicine
Sackler Medicine building
room 1003
Tel:  (972)-3-6406642
Fax: (972)-3-6409360
Personal Website:

Postal Address:Sackler School of Medicine
Tel Aviv University
Tel Aviv 69978

Research Interest

Our primary interest is the genetic basis of hereditary hearing loss or deafness. Our group is working towards the identification, characterization and regulation of genes associated with hereditary hearing loss. For gene discovery, we focus on the Israeli Jewish and Palestinian Arab populations in the Middle East. Our studies have encompassed the prevalence of connexin 26 mutations in these populations, the most common form of deafness, to the identification of mutations in over 30 genes, since this is a genetically heterogeneous disease. We are employing deep sequencing, also known as massively parallel sequencing, to identify mutations using the latest genomic technology. Our work has provided the link between gene discovery and clinical diagnosis in genetic clinics in medical centers throughout Israel. In addition, we have studied the auditory and vestibular systems of a dozen mouse mutants, focusing on mutation identification, morphological and functional analysis of the organ of Corti and its cells, and behavioral analysis of hearing and balance disorders. This has allowed us to define the pathways leading to deafness in mouse models for human deafness. Most recently, we have demonstrated that microRNAs are essential for development and function of inner ear hair cells in vertebrates through microRNA expression, mouse mutants and target identification

Selected Publications

  • Peer-reviewed manuscripts
    1. Epstein, C.J., Avraham, K.B., Lovett, M., Smith, S., Elroy-Stein, O., Rotman, G., Bry, C. and Groner, Y. (1987) Transgenic mice with increased Cu/Zn-superoxide dismutase activity: Animal model of dosage effects in Down syndrome. Proc. Natl. Acad. Sci. USA 84: 8044-8048.
    2. Avraham, K.B., Schickler, M., Sapoznikov, D., Yarom, R. and Groner, Y. (1988) Down's syndrome: Abnormal neuromuscular junction in tongue of transgenic mice with elevated levels of human Cu/Zn-superoxide dismutase. Cell 54: 823-829.
    3. Yarom, R., Sapoznikov, D., Havivi, Y., Avraham, K.B., Schickler, M. and Groner, Y. (1988) Premature aging changes in neuromuscular junctions of transgenic mice with an extra human CuZnSOD gene: A model for tongue pathology in Down's syndrome. J. Neurol. Sci. 88: 41-53.
    4. Schickler, M., Knobler, H., Avraham, K.B., Elroy-Stein, O. and Groner, Y. (1989) Diminished serotonin uptake in platelets of transgenic mice with increased Cu/Zn-superoxide dismutase activity. EMBO J. 8: 1385-1392.
    5. Avraham, K.B., Sugarman, H., Rotshenker, S. and Groner, Y. (1991) Down’s syndrome: Morphological remodelling and increased complexity in the neuromuscular junction of transgenic CuZn-superoxide dismutase mice. J. Neurocyt. 20: 208-215.
    6. White, C.W., Avraham, K.B., Shanley, P. and Groner, Y. (1991) Transgenic mice with expression of elevated levels of copper-zinc superoxide dismutase in the lungs are resistant to pulmonary oxygen toxicity. J. Clin. Invest. 87: 2162-2168.
    7. Avraham, K.B., Prezioso, V.R., Chen, W.S., Lai, E., Sladek, F.M., Zhong, W., Darnell, J.E., Jr., Jenkins, N.A. and Copeland, N.G. (1991) Murine chromosomal location of four hepatocyte-enriched transcription factors: HNF-3a, HNF-3b, HNF-3g, and HNF-4. Genomics 13: 264-268.
    8. Shanley, P.F., White, C.W., Avraham, K.B., Groner, Y. and Burke, T.J. (1992) Use of transgenic animals to study disease models: Hyperoxic lung injury and ischemic acute renal failure in "high SOD" mice. Renal Fail. 14: 391-394.
    9. Avraham, K.B., Cho, B.C., Gilbert, D., Fujii, H., Okamoto, K., Shimazaki, T., Ito, T., Shoji, H., Wakamatsu, Y., Kondoh, H., Takahashi, N., Muramatsu, M., Hamada, H., Copeland, N.G. and Jenkins, N.A. (1993) Murine chromosomal location of four class III POU transcription factors. Genomics 18: 131-133.
    10. White, C.W., Nguyen, D. H., Suzuki, K., Taniguchi, N., Rusakow, L.S., Avraham, K.B. and Groner, Y. (1993) Expression of manganese superoxide dismutase is not altered in transgenic mice with elevated level of copper-zinc superoxide dismutase. Free Rad. Biol. Med. 15: 629-636.
    11. Okazaki, T., Yoshida, B.N., Avraham, K.B., Wang, H., Wuenschell, C.W., Jenkins, N.A., Copeland, N.G., Anderson, D.J. and Mori, N. (1993) Molecular diversity of the SCG10/stathmin gene family in the mouse. Genomics 18: 360-373.
    12. Avraham, K.B., Givol, D., Avivi, A., Yayon, A., Copeland, N.G. and Jenkins, N.A. (1994) Mapping of murine fibroblast growth factor receptors refines regions of homology between mouse and human chromosomes. Genomics 21: 656-658.
    13. Avraham, K.B., Fletcher, C., Overdier, D.G., Clevidence, D.E., Lai, E., Costa, R.H., Jenkins, N.A. and Copeland, N.G. (1995) Murine chromosomal location of eight members of the hepatocyte nuclear factor 3/fork head winged helix family of transcription factors. Genomics 25: 388-393.
    14. Avraham, K.B., Levanon, D., Negreanu, V., Bernstein, Y., Groner, Y., Copeland, N.G. and Jenkins, N.A. (1995) Mapping of the murine homolog of the human runt domain gene, AML2, to the distal region of mouse chromosome 4. Genomics 25: 603-605.
    15. Chen, H., Thalmann, I., Adams, J. C., Avraham, K.B., Copeland, N.G., Jenkins, N.A., Beier, D.R., Corey, D.P., Thalmann, R. and Duyk, G.M. (1995) cDNA cloning, tissue distribution, and chromosomal localization of Ocp2, a gene encoding a putative transcription-associated factor predominantly expressed in the auditory organs. Genomics 27: 389-398.
    16. Santoro, T., Maguire, J., McBride, O.W., Avraham, K.B., Copeland, N.G., Jenkins, N.A. and Kelly, K. (1995) Chromosomal organization and transcriptional regulation of human GEM and localization of the human and mouse GEM loci encoding an inducilble ras-like protein. Genomics 30: 558-564.
    17. Avraham, K.B., Hasson, T., Steel, K.P., Kingsley, D.M., Russell, L.B., Mooseker, M.S., Copeland, N.G. and Jenkins, N.A. (1995) The mouse Snell’s waltzer deafness gene encodes an unconventional myosin required for the structural integrity of inner ear hair cells. Nature Genet. 11: 369-375.
    18. Pecker, I., Avraham, K.B., Gilbert, D.J., Savitsky, K., Rotman, G., Harnik, R., Fukao, T., Schrock, E., Hirotsune, S., Tagle, D.A., Collins, F.S., Wynshaw-Boris, A., Ried, T., Copeland, N.G., Jenkins, N.A., Shiloh, Y. and Ziv, Y. (1996) Identification and chromosomal localization of Atm, the mouse homolog of the ataxia-telangiectasia gene. Genomics 35: 39-45.
    19. Berger, R., Theodor, L., Shoham, J., Gokkel, E., Brok-Simoni, F., Avraham, K.B., Copeland, N.G., Jenkins, N.A., Rechavi, G. and Simon, A.J. (1996) The molecular characterization and localization of the mouse Thymopoietin (Tmpo)/lamina-associated polypeptide 2 (LAP2) gene and its alternatively spliced products. Genome Res. 6: 361-370. 
    20. Hasson, T., Skowron, J.F., Gilbert, D.J., Avraham, K.B., Perry, W.L., Bement, W.M., Anderson, B.L., Sherr, E.H., Chen, Z.-Y., Greene, L.A., Ward, D.C., Corey, D.P., Mooseker, M.S., Copeland, N.G. and Jenkins, N.A. (1996) Mapping of unconventional myosins in mouse and man. Genomics 36: 431-439.
    21. Self, T.J., Avraham, K.B. and Steel, K.P. (1997) A scanning electron microscope study of the development of the mouse mutant Snell's waltzer. Brit. J. Audiol. 31: 82.
    22. Avraham, K.B., Hasson, T., Sobe, T., Balsara, B.,Testa, J.R., Skvorak, A.B.,Morton, C.C., Copeland, N.G. and Jenkins, N.A. (1997) Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice. Hum. Molec. Genet. 6: 1225-1231.
    23. Vahava, O., Morell, R., Lynch, E.D., Weiss, S., Kagan, M.E., Ahituv, N., Morrow, J.E., Lee, M.K., Skvorak, A.B., Morton, C.C., Blumenfeld, A., Frydman, M., Friedman, T.B., King, M.-C. and Avraham, K.B. (1998) Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans. Science 279: 1950-1954.
    24. Varfolomeev, E.E., Schuchmann, M., Luria, V., Chiannilkulchai, N., Beckmann, J.S., Mett, I.L., Rebrikov, D., Brodianski, V.M., Kemper, O.C., Kollet, O., Lapidot, T.S., Soffer, D., Sobe, T., Avraham, K.B., Goncharov, T., Holtmann, H., Lonai, P. and Wallach, D. (1998) Targeted disruption of the mouse caspase-8 gene ablates cell-death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9: 267-276.
    25. Sobe, T., Erlich, P., Berry, A., Korostichevsky, M., Vreugde, S., Shohat, M., Avraham, K.B. and Bonné-Tamir, B. (1999) High frequency of the deafness-associated 167delT mutation in the connexin 26 (GJB2) gene in Israeli Ashkenazim. Am. J. Med. Genet. 86: 499-500.
    26. Self, T., Sobe, T., Copeland, N.G., Jenkins, N.A., Avraham, K.B. and Steel, K.P. (1999) Role of myosin VI in the differentiation of cochlear hair cells. Dev. Biol. 214: 331-341.
    27. Kiernan, A.E., Zalzman, M., Fuchs, H., Hrabe de Angelis, M., Balling, R., Steel, K.P. and Avraham K.B. (1999) Tailchaser (Tlc): a new mouse mutation affecting hair cell survival and hair bundle morphogenesis. J. Neurocytol. 28: 969-985.
    28. Sobe, T., Vreugde, S., Shahin, H., Davis, N., Berlin, M., Kanaan, M., Yaron, Y., Orr-Urtreger, A., Frydman, M., Shohat, M. and Avraham, K.B. (2000) The prevalence and expression of inherited connexin 26 mutations associated with nonsyndromic hearing loss in the Israeli population. Hum. Genet. 106: 50-57.
    29. Frydman, M.*, Vreugde, S.*, Nageris, B.I., Weiss, S., Vahava, O. and Avraham, K.B. (2000) Clinical characterization of genetic hearing loss caused by a mutation in the POU4F3 transcription factor. Arch. Otolaryn. Head Neck Surg. 126: 633-637.
    30. Hrabe de Angelis, M., Flaswinkel, H, Fuchs, H., Rathkolb, B., Soewarto, D., Marschall, S., Heffner, S., Pargent, W., Wuensch, K., Jung, M., Reis, A., Richter, T., Alessandrini, F., Jakob, T., Fuchs, E., Kolb, H., Kremmer, E., Schaeble, K., Rollinski, B., Roscher, A., Peters, C., Meitinger, T., Strom, T., Steckler, T., Holsboer, F., Klopstock, T., Gekeler, F., Schindewolf, C., Jung, T., Avraham, K.B., Behrendt, H., Ring, J., Zimmer, A., Schughart, K., Pfeffer, K., Wolf, E. and Balling, R. (2000) Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nature Genet. 25: 444-447.
    31. Ahituv, N., Sobe, T., Robertson, N.G., Morton, C.C., Taggart, R.T. and Avraham, K.B. (2000) Genomic structure of the human unconventional myosin VI gene. Gene 261: 269-275.
    32. Kiernan, A.E.*, Ahituv, N.*, Fuchs, H., Balling, R., Avraham, K.B., Steel, K.P. and Hrabé de Angelis, M. (2001) The Notch ligand Jagged1 is required for inner ear sensory development. Proc. Natl. Acad. Sci. USA. 98: 3873-3878.
    33. López-Bigas, N., Olivé, M., Rabionet, R., Ben-David, O., Martínez-Matos, J.A., Olga Bravo, O., Banchs, I., Volpini, V., Gasparini, P., Avraham, K.B., Ferrer, I., Lourdes Arbonés, M. and Estivill, X. (2001) Connexin 31 (GJB3) amino acid deletion in peripheral neuropathy. Hum. Molec. Genet. 10: 947-952.
    34. Melchionda, S.*, Ahituv, N.*, Bisceglia, L., Sobe, T., Glaser, F., Rabionet, R., Arbones, M.L., Notarangelo, A., Di Iorio, E., Carella, M., Zelante, L., Estivill, X. Avraham, K.B. and Gasparini, P. (2001) MYO6, the human homologue of the gene responsible for deafness in Snell’s waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss. Am. J.Hum. Genet. 69: 635-640.
    35. Shahin, H., Walsh, T., Sobe, T., Lynch, E., King, M.-C., Avraham, K.B. and Kanaan, M. (2002) Genetics of congenital deafness in the Palestinian population: Multiple connexin 26 alleles with shared origins in the Middle East. Hum. Genet. 110 :284–289.
    36. Vreugde, S.*, Erven, A.*, C.J., Marcotti, W., Fuchs, H., Kurima, K., Wilcox, E.R., Friedman, T.B., Griffith, A.J., Balling, R., Hrabé de Angelis, M., Avraham, K.B. and Steel, K.P. (2002) Beethoven, a mouse model for dominant, progressive hearing loss DFNA36. Nature Genet. 30: 257-258.
    37. Zwaenepoel, I., Mustapha, M., Leibovici, M., Verpy, E., Goodyear, R., Liu, X. Z., Nouaille, S., Nance, W.E., Kanaan, M., Avraham, K.B., Tekaia, F., Loiselet, J., Lathrop M.,Richardson, G. and Petit, C. (2002) Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22. Proc. Natl. Acad. Sci. USA 99: 6240-6245.
    38. Gottfried, I., Landau, M., Glaser, F., Di, W.-L., Ophir, J., Mevorah, B., Ben-Tal, N., Kelsell, D.P. and Avraham, K.B. (2002) A mutation in GJB3 is associated with recessive erythrokeratodermia variabilis (EKV) and leads to defective trafficking of the connexin 31 protein. Hum. Molec. Genet. 11: 1311-1316.
    39. Walsh, T., Walsh, V., Vreudge, S., Hertzano, R., Shahin, H., Haika, S., Lee, M.K., Kanaan, M., King, M.-C. and Avraham, K.B. (2002) From flies' eyes to our ears: Mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30. Proc. Natl. Acad. Sci. USA. 99: 7518-7523.
    40. Adato, A., Vreugde, S., Joensuu, T., Avidan, N., Hamalainen, R., Belenkiy, O., Olender, T., Bonne-Tamir, B., Ben-Asher, E., Espinos, C., Millán, J.M., Lehesjoki, A.-E., Flannery, J.G., Avraham, K.B., Pietrokovski, S., Sankila, E.-M., Beckmann, J.S. and Lancet, D. (2002) USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses. Eur. J. Hum. Genet. 10: 339-350.
    41. Ben-Yosef, T., Ness, S.L., Madeo, A.C., Bar-Lev, A., Wolfman, J.H., Ahmed, Z.M., Desnik, R.J., Willner, J.P., Avraham, K.B., Ostrer, H., Oddoux, C., Griffith, A.J. and Friedman, T.B. (2003) A mutation of PCDH15 among Ashkenazi Jews with the Type 1 Usher syndrome. N. Engl. J. Med. 348: 1664-1670.
    42. RamShankar, M., Girirajan, S., Dagan, O., Ravi Shankar, H.M., Jalvi, R., Rangasayee, R., Avraham, K.B., Anand, A. (2003) Contribution of connexin 26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India. J. Med. Genet. 40: e68.
    43. Donaudy, F., Ferrara, A., Esposito, L., Hertzano, R., Ben-David, O., Bell, R.E., Melchionda, S., Zelante, L., Avraham, K.B., Gasparini, P. (2003) Multiple mutations of MYO1A, a cochlear expressed gene, in sensorineural hearing loss. Am. J.Hum. Genet. 72: 1571-1577.
    44. Ness, S.L., Ben-Yosef, T., Bar-Lev, A., Madeo, A.C., Brewer, C.C., Avraham,K.B., Kornreich, R., Desnick, R.J., Willner, J.P., Friedman, T.B. and Griffith, A.J. (2003) Genetic homogeneity and phenotypic variability among Ashkenazi Jews with Usher syndrome type III. J. Med. Genet. 40: 767-772.
    45. Karolyi, I.J., Probst, F.J., Beyer, L., Odeh, H., Dootz, G., Cha, K.B., Martin, D.M., Avraham, K.B., Kohrman, D., Dolan, D.F., Raphael, Y. and Camper, S.A. (2003) Myo15 gene function is independent of Myo6, Myo7a, and pirouette genes in cochlear stereocilia. Hum. Molec. Genet. 12: 2797-2805.
    46. del Castillo, I., Moreno-Pelayo, M.A., del Castillo, F.J., Brownstein, Z., Marlin, S., Adina, Q., Cockburn, D.J., Pandya, A., Siemering, K.R., Chamberlin, G.P., Ballana, E., Wuyts, W., Maciel-Guerra, A.T., Álvarez, A., Villamar, M., Shohat, M., Abeliovich, D., Dahl, H.-H.M., Estivill, X., Gasparini, P., Hutchin, T., Nance, W.E., Sartorato, E.L., Smith, R.J.H., Van Camp, G., Avraham, K.B., Petit, C. and Moreno, F. (2003) Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing impaired subjects: a multicentric study. Am. J. Hum. Genet. 73:1452-1458.
    47. Weiss, S., Gottfried, I., Mayrose, I., Khare, S.L., Xiang, M., Dawson, S.J. and Avraham, K.B. (2003) The DFNA15 deafness mutation affects POU4F3 protein stability, localization and transcriptional activity. Mol. Cell. Biol. 23: 7957-7964.
    48. Brownstein, Z., Ben-Yosef, T., Dagan, O., Frydman, M., Abeliovich, D., Sagi, M., Abraham, F.A., Taitelbaum-Swead, R., Shohat, M., Hildesheimer, M., Friedman, T.B. and Avraham, K.B. (2004) The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosa. Pediatr. Res. 55: 995-1000.
    49. Seiler, C.*, Ben-David, O.*, Sidi, S., Hendrich, O., Rusch, A., Burnside, B., Avraham, K.B. and Nicolson, T. (2004) Myosin VI is required for structural integrity of the apical surface of sensory hair cells in zebrafish. Dev. Biol. 272: 328-338.
    50. Ahituv, N.*, Erven, A.*, Fuchs, H., Guy, K., Ashery-Padan, R., Williams, T., Hrabé de Angelis, M., Avraham, K.B. and Steel, K.P. (2004) An ENU-induced mutation in AP-2a leads to middle ear and ocular defects in Doarad mice. Mamm. Genome 15: 424-432.
    51. Hertzano, R., Montcouquiol, M., Rashi-Elkeles, S., Elkon, R., Yücel, R., Frankel, W.N., Rechavi, G., Möröy, T., Friedman, T.B., Kelley, M.W. and Avraham, K.B. (2004) Transcription profiling of inner ears from Pou4f3ddl/ddl identifies Gfi1 as a target of the Pou4f3 deafness gene. Hum. Molec. Genet. 13: 2143-2153.
    52. Rhodes, C.R.*, Hertzano, R.*, Fuchs, H., Bell, R.E., Hrabé de Angelis, M., Steel, K.P. and Avraham, K.B. (2004) A Myo7a mutation co-segregates with stereocilia defects and low frequency hearing impairment. Mamm. Genome 15: 686-697.
    53. Clough, R.L., Sud, R., Davis-Silberman, N., Hertzano, R., Avraham, K.B., Holley, M. and Dawson, S.J. (2004) Brn-3c (POU4F3) regulates BDNF and NT-3 promoter activity. Biochem. Biophys. Res. Commun. 324: 372-381.
    54. del Castillo, F.J., Rodrıguez-Ballesteros, M., lvarez, M., Hutchin, T., Leonardi, E., de Oliveira, C.A., Azaiez, H., Brownstein, Z., Avenarius, M.R., Marlin, S., Pandya, A., Shahin, H., Siemering, K.R., Weil, D., Wuyts, W., Aguirre, L.A., Martın, Moreno-Pelayo, M.A., Villamar, M., Avraham, K.B., Dahl, H.-H.M., Kanaan, M., Nance, W.E.,, Petit, C., Smith, R.J.H., Van Camp, G., Sartorato, E.L., Murgia, A., Moreno, F. and del Castillo, I. (2005) A novel deletion involving the connexin-30 gene, del(GJB6-D13S1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. J. Med. Genet. 42: 588–594.
    55. Shahin, H., Walsh, T., Sobe, T., Abu Sa'ed, J., Abu Rayan, A., Lynch, E.D., Lee, M.K., Avraham, K.B., King, M.-C. and Kanaan, M. (2005) Mutations in a novel isoform of TRIOBP that encodes a filamentous-actin binding protein are responsible for DFNB28 recessive nonsyndromic hearing loss. Am. J. Hum. Genet. 78: 144-152.
    56. Snoeckx, R.L., Huygen, P.L.M., Feldmann, D., Marlin, S., Denoyelle, F., Waligora, J, Mueller-Malesinska, M., Pollak, A., Ploski, R., Murgia, A., Orzan, E., Castorina, P., Ambrosetti, U., Nowakowska-Szyrwinska, E., Bal, J., Wiszniewski, W., Janecke, A.R., Nekahm-Heis, D., Seeman, P., Olga Bendova, O., Kenna, M.A., Frangulov, A., Rehm, H.L., Tekin, M., Incesulu, A., Dahl, H.-H.M., du Sart, D., Jenkins, L., Lucas, D., Bitner-Glindzicz, M., Avraham, K.B., Brownstein, Z., del Castillo, I., Moreno, F., Blin, N., Pfister, M., Sziklai, I., Toth, T., Kelley, P.M., Cohn, E.S., Van Maldergem, L., Hilbert, P., Roux, A.-F., Mondain, M., Hoefsloot, L.H., Cremers, C.W.R.J., Löppönen, T., Löppönen, H., Parving, A., Gronskov, K., Schrijver, I., Roberson, J., Gualandi, F., Martini, A., Lina-Granade, G., Pallares-Ruiz, N., Correia, C., Fialho, G., Cryns, K., Hilgert, N., Van de Heyning, P., Nishimura, C.J., Smith, R.J.H. and Van Camp, G. (2005) GJB2 mutations and degree of hearing loss: a multi-center study. Am. J. Hum. Genet. 77: 945-957.
    57. Fiolka, K., Hertzano, R., Vassen, L., Zeng, H., Hermesh, O., Avraham, K.B., Dührsen, U. and Möröy, T. (2006) Gfi1 and Gfi1b act equivalently in hematopoiesis but have distinct, nonoverlapping functions in inner ear development. EMBO Rep. 7: 326-333.
    58. Taitelbaum-Swead, R., Brownstein, Z., Muchnik, C., Megirov, L., Kishon-Rabin, L., Kronenberg, J., Hildesheimer, M. and Avraham, K.B. (2006) Connexin-associated deafness and speech perception outcome of cochlear implantation. Arch. Otolaryn. Head Neck Surg. 132: 495-500.
    59. Walsh, T., Abu Rayan, A., Abu Sa’ed, J., Shahin, H., Lee, M.K., Hirschberg, K., Tekin, M., Avraham, K.B., King, M.-C. and Kanaan, M. (2006) Genomic analysis of a heterogeneous mendelian phenotype: multiple novel alleles for inherited hearing loss in the Palestinian population. Hum. Gen. 2: 203-211.
    60. Brownstein, Z., Goldfarb, A., Levi, H., Frydman, M. and Avraham, K.B. (2006) Chromosomal mapping and phenotypic characterization of hereditary otosclerosis linked to the OTSC4 locus. Arch. Otolaryn. Head Neck Surg. 132: 416-424.
    61. Fleishman, S.J.*, Sabag, A.D.*, Ophir, E., Avraham, K.B. and Ben-Tal, N. (2006) The structural context of disease-causing mutations in gap junctions. J. Biol. Chem. 281: 28958-28963.
    62. Hertzano, R., Dror, A.A., Montcouquiol, M., Ahmed, Z., Ellsworth, B., Camper, S., Friedman, T.B., Kelley, M.W. and Avraham, K.B. (2007) Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory, but not in the vestibular system. Eur. J. Neurosci. 25:999-1005.
    63. Brownstein, Z.N., Dror, A.A., Gilony, D., Migirov, L., Hirschberg, K. and Avraham, K.B. (2008) A novel PDS deafness mutation is retained in the endoplasmic reticulum. Arch. Otolaryn. Head Neck Surg. 134:403-407.
    64. Hertzano, R.*, Shalit, E.*, Rzadzinska, A.K.*, Dror, A.A., Song, L., Ron, U., Tan, J.T., Starovolsky Shitrit, A., Fuchs, H., Hasson, T., Ben-Tal, N., Sweeney, H.L., Hrabe de Angelis, M., Steel, K.P. and Avraham, K.B. (2008) A Myo6 mutation destroys coordination between the myosin heads, revealing new functions of myosin VI in the stereocilia of mammalian inner ear hair cells. PLoS Genet. 4:e1000207.
    65. Geller, S.F., Guerin, K.I., Visel, M., Pham, A., Lee, E.S., Dror, A.A., Avraham, K.B., Hayashi, T., Ray, C.A., Reh, T.A., Bermingham-McDonogh, O., Triffo, W.J., Bao, S., Isosomppi, J., Västinsalo, H., Sankila, E.M. and Flannery, J.G. (2009) CLRN1 is nonessential in the mouse retina but is required for cochlear hair cell development. PLoS Genet. 5:e1000607.
    66. Avni, R., Elkan, T., Dror, A.A., Shefer, S., Eilam, D., Avraham, K.B. and Mintz, M. (2009) Mice with vestibular deficiency display hyperactivity, disorientation, and signs of anxiety. Behav. Brain Res. 14202: 210-217.
    67. Friedman, L.M., Dror, A.A., Mor, E., Tenne, T., Toren, G., Satoh, T., Biesemeier, D.J., Shomron, N., Fekete, D.M., Hornstein, E. and Avraham, K.B. (2009) MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. Proc. Natl. Acad. Sci. USA, 106: 7915-7920.
    68. Shahin, H., Walsh, T., Rayyan, A.A., Lee, M.K., Higgins, J., Dickel, D., Lewis, K., Thompson, J., Baker, C., Nord, A.S., Stray, S., Gurwitz, D., Avraham, K.B., King, M.C. and Kanaan, M. (2009) Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families. Eur. J. Hum. Genet. 18: 407-413.
    69. Shefer, S., Gordon, C.R., Avraham, K.B. and Mintz, M. (2010) Progressive vestibular mutation leads to elevated anxiety. Brain Res. 1317: 157–164.
    70. Shahin, H., Rahil, M., Abu Rayan, A., Avraham, K.B., King, M.-C., Kanaan, M. and Walsh, T. (2010) Nonsense mutation of the stereociliar membrane protein gene PTPRQ in human hearing loss DFNB84. J. Med. Gen. 47: 643-645.
    71. Wainreb, G., Ashkenazy, H., Bromberg, Y., Starovolsky-Shitrit, A., Haliloglu, T., Ruppin, E., Avraham, K.B., Rost, B. and Ben-Tal, N. (2010) MuD: an interactive web server for the prediction of non-neutral substitutions using protein structural data. Nucleic Acids Res. 38: W523-528.
    72. Walsh, T., Shahin, H., Elkan-Miller, T., Lee, M.K., Thornton, A.M., Roeb, W., Abu Rayyan, A., Loulus, S., Avraham, K.B., King, M.-C. and Kanaan, M. (2010) Whole exome sequencing and homozygosity mapping identify mutation in the cell polarity protein GPSM2 as the cause of non-syndromic hearing loss DFNB82. Am. J. Hum. Genet. 87: 1-5.
    73. Walsh, T., Pierce, S.B., Lenz, D.R., Brownstein, Z., Dagan-Rosenfeld, O., Shahin, H., Roeb, W., McCarthy, S., Nord, A.S., Gordon, C.R., Ben-Neriah, Z., Sebat, J., Kanaan, M., Lee, M.K., Frydman, M., King, M.-C. and Avraham, K.B. (2010) Genomic duplication and over-expression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive non-syndromic hearing loss DFNA51. Am. J. Hum. Genet87: 101-109..
    74. Dror, A.A., Politi, Y., Shahin, H., Lenz, D.R., Dossena, S., Nofziger, C., Fuchs, H., Hrabé de Angelis, M.,Markus, P., Weiner, S. and Avraham, K.B. (2010). Calcium oxalate stone formation in the inner ear as a result of an Slc26a4 mutation. J. Biol. Chem. 285: 21724-21735.
    75. Atar, O. and Avraham, K.B. (2010) Anti-apoptotic factor z-val-ala-asp-fluoromethylketone promotes the survival of cochlear hair cells in a mouse model for human deafness. Neurosci. 168: 851–857.
    76. Lenz, D.R., Dror, A.A., Wekselman, G. Fuchs, H., Hrabé de Angelis, M. and Avraham, K.B. (2010) The inner ear phenotype of Volchok (Vlk): an ENU-induced mouse model for CHARGE syndrome. Audiol. Med. 8: 110-119.
    77. Walsh, V.L., Raviv, D., Dror, A.A., Shahin, H., Walsh, T., Kanaan, M.N., Avraham, K.B. and King, M.-C. (2010) A mouse model for human hearing loss DFNB30 due to loss of function of myosin IIIA. Mamm. Genome 22: 170-177.
    78. Wainreb, G., Ashkenazy, H., Bromberg, Y., Starovolsky-Shitrit, A., Haliloglu, T., Ruppin, E., Avraham, K.B., Rost, B. and Ben-Tal, N. (2010) MuD: an interactive web server for the prediction of non-neutral substitutions using protein structural data. Nucleic Acids Res. 38: W523-528.
    79. Paz, A., Brownstein, Z., Ber, Y., Bialik, S., David, E., Sagir, D., Ulitsky, I., Elkon, R., Kimchi, A., Avraham, K.B., Shiloh, Y. and Shamir, R. (2011) SPIKE: a database of highly curated human signaling pathways. Nucleic Acids Res. 39: D793-793.
    80. Elkan-Miller, T., Ulitsky, I., Hertzano, R., Rudnicki, A., Dror, A.A., Lenz, D.R., Elkon, R., Irmler, M., Beckers, J., Shamir, R. and Avraham, K.B. (2011) Integration of transcriptomics, proteomics, and microRNA analyses reveals novel microRNA regulation of targets in the mammalian inner ear. PLoS One 6: e18195.
    81. Brownstein, Z., Friedman, L.M., Shahin, H., Oron-Karni, V., Kol, N., Abu Rayyan, A., Parzefall, T., Lev, D., Shalev, S., Frydman, M., Davidov, B., Shohat, M., Rahile, M., Lieberman, S., Levy-Lahad, E., Lee, M., Shomron, N., King, M.-C., Walsh, T., Kanaan, M. and Avraham, K.B. (2011) Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in Middle Eastern families. Genome Biol. 12: R89.
    82. Rosengauer, E., Hartwich, H., Hartmann, A.M., Rudnicki, A., Satheesh, S.V., Avraham, K.B. and Nothwang, H.G. (2012) Egr2::Cre mediated conditional ablation of Dicer disrupts histogenesis of mammalian central auditory nuclei. PLoS One. 7:e49503.
    83. Horn, H.F.,* Brownstein, Z.,* Lenz, D.R.,Shivatzki, S., Dror, A.A., Dagan-Rosenfeld, O., Friedman, L.M., Roux, K.J., Kozlov, S., Jeang, K.-T.,Frydman, M.,Burke, B., Stewart, C.L., and Avraham, K.B.The LINC complex is essential for hearing. In press.
    *These authors contributed equally to the work.
    1. Avraham, K.B. (1997). Motors, channels and the sounds of silence. Nature Med. 3: 608-609.
    2. Avraham, K.B. (1997). Sounds from the cochlea. Nature 390: 559-560.
    3. Avraham, K.B. (1998). Hear come more genes! Nature Med. 4: 1238-1239.
    4. Ben-David, O. and Avraham, K.B. (1999) The Genetics of Deafness. J. Israeli Speech Lang. Hear. Assoc. 21: 3-12.
    5. Ben-David, O. and Avraham, K.B. (1999) The Genetics of Hearing Loss. J. Basic Clin. Physiol. Pharmacol. 10: 163-171.
    6. Friedman, T.B., Sellers, J.R. and Avraham, K.B. (1999) Unconventional myosins and the genetics of hearing loss. Am. J. Med. Genet. (Sem. Med. Genet.) 89: 147-157.
    7. Ahituv, N. and Avraham, K.B. (2000) Auditory and vestibular mouse mutants: models for human deafness. J. Basic Clin. Physiol. Pharmacol. 11: 181-191.
    8. Avraham, K.B. (2001) Modifying with mitochondria. Nature Genet. 27: 136-137.
    9. Avraham, K.B. (2001) Inherited connexin mutations associated with hearing loss. Cell Adhes. Comm. 8: 419-424.
    10. Ahituv, N. and Avraham, K.B. (2002) Mouse models for human deafness: Current tools for new fashions. Trends Mol. Med. 8: 447-451.
    11. Goldfarb, A. and Avraham. K.B. (2002) Genetics of deafness: recent advances and clinical implications. J. Basic Clin. Physiol. Pharmacol. 13: 75-88.
    12. Avraham, K.B. (2003) Mouse models for deafness: lessons for the human inner ear and hearing loss. Ear Hear. 24: 332-341.
    13. Avraham. K.B. and Raphael, Y. (2003) Prospects for gene therapy in hearing loss. J. Basic Clin. Physiol. Pharmacol. 14: 77-83.
    14. Skinner, H., Abdeen, Z., Abdeen, H., Aber, P., Al-Masri, M., Attias, J., Avraham, K.B., Carmi, R., Chalin, C., El Nasser, Z., Hijazi, M., Othman Jebara, R., Kanaan, M., Pratt, H., Raad, F., Roth, Y., Williams, A.P. and Noyek, A. (2005) Promoting Arab and Israeli cooperation: a model for peacebuilding through health initiatives. Lancet 365: 1274-1277.
    15. Atar, O. and Avraham, K.B. (2005) Therapeutics of hearing loss: expectations vs. reality. Drug Discov. Today 10: 1323-1330.
    16. Sabag-Dgani, A., Dagan, O. and Avraham, K.B. (2005) Connexins in hearing loss: a comprehensive overview. J. Basic Clin. Physiol. Pharmacol. 16: 101-116.
    17. Brownstein, Z. and Avraham, K.B. (2006) Future trends and potential for treatment of sensorineural hearing loss. Semin. Hear. 27: 193-204.
    18. Friedman, L., Dror, A.A. and Avraham, K.B. (2007) Mouse models developed to study inner ear development and hereditary hearing loss. Int. J. Dev. Biol. 51: 609-631.
    19. Friedman, L.M. and Avraham, K.B. (2009) MicroRNAs and epigenetic regulation in the mammalian inner ear: implications for deafness. Mamm. Genome 20: 581-603.
    20. Brownstein, Z. and Avraham, K.B. (2009) Deafness genes in Israel: implications for diagnostics in the clinic. Pediatr. Res. 66: 128-134.
    21. Dror, A.A. and Avraham, K.B. (2009) Hearing loss: Mechanisms revealed by genetics and cell biology. Annu. Rev. Genet. 43: 411-437.
    22. Raviv, D., Dror, A.A. and Avraham, K.B. (2010) Hearing loss: a common disorder caused by many rare alleles. Ann. N.Y. Acad. Sci. 1214: 168-179.
    23. Dror, A.A. and Avraham, K.B. (2010) Hearing impairment: a panoply of genes and functions. Neuron 68: 293-308.
    24. Ozçelik, T., Kanaan, M., Avraham, K.B., Yannoukakos, D., Mégarbané, A., Tadmouri, G.O., Middleton, L., Romeo, G., King, M.C. and Levy-Lahad, E. (2010) Collaborative genomics for human health and cooperation in the Mediterranean region. Nat. Genet. 42: 641-645.
    25. Lenz, D.R. and Avraham, K.B. (2011) Hereditary hearing loss: From human mutation to mechanism. Hear. Res. 281: 3-10.
    26. Dror, A., Brownstein, Z. and Avraham, K.B. (2011) Integration of human and mouse genetics reveals pendrin function in hearing and deafness. Cell. Physiol. Biochem, 28:535-544.
    27. Dossena, S., Nofziger, C., Brownstein, Z., Kanaan, M., Avraham, K.B. and Paulmichl, P. (2011) Functional characterization of pendrin mutations found in the Israeli and Palestinian populations. Cell. Physiol. Biochem, 28: 28:477-484.
    28. Brownstein, Z., Bhonker, Y., Avraham, K.B. (2012) High-throughput sequencing to decipher the genetic heterogeneity of deafness. Genome Biol. 13:245.
    29. Rudnicki, A. and Avraham, K.B. (2012) microRNAs: the art of silencing in the ear. EMBO Mol Med 4:1-11.
    30. Avraham, K.B. and Kanaan, M. (2012) Genomic advances for gene discovery in hereditary hearing loss. J Basic Clin Physiol Pharmacol. 23:93-97.
    Chapters in Books
    1. Avraham, K.B. (2000) DFNA15. In: Advances in Oto-Rhino-Laryngology: Genetics in Oto-Rhino-Laryngology (K. Kitamura and Steel, K.P., eds). S. Karger AG, Basel, Switzerland. pp. 107-115.
    2. Steel, K.P., Self, T.J., Liu, X.-Z., Avraham, K.B. and Brown, S.D.M. (2000) Of Mice and Men (and Myosins). In: The Genetics of Deafness (C.I. Berlin and B. Keats, eds). Singular Publishing Group Inc., San Diego and London. pp. 1-30.
    3. Avraham, K.B. (2001) Positional Candidate Cloning of Genes from Mouse Mutants. In: Methods in Molecular Biology: Gene Knockout Protocols (M.J. Timms and I. Kola, eds.). Humana Press, Inc., Totowa, NJ. pp. 369-379.
    4. Avraham, K. B. and Hasson, T. (2001) Genes and Mutations in Hearing Impairment. In: Springer Handbook of Auditory: Genetics and Auditory Disorders (B. Keats, A.N. Popper, and R.R. Fay, eds.). Springer-Verlag, NY. pp. 23-44.
    5. Avraham, K. B. (2002) The Genetics of Deafness: A Model for Genomic and Biological Complexity. In: Ernst Schering Research Foundation Workshop 36 (A. Rosenthal, ed.). Springer–Verlag, Heidelberg. pp. 71-93.
    6. Gottfried, I., Huygen, P.L.M. and Avraham, K.B. (2002) The Clinical Presentation of DFNA15/POU4F3. In: Advances in ORL (R.J.H. Smith and C.W.R.J. Cremers, eds.). Karger AG, Basel. pp. 92-97.
    7. Avraham, K.B. (2003) Molecular Motors in Sensory Defects. In: Molecular Motors (M. Schliwa, ed.). WILEY-VCH, Berlin. pp. 511-537.
    8. Hertzano, R. and Avraham, K.B. (2004) Involvement of the POU-Domain Transcription Factors in Human Hereditary Deafness. In: Genetic Hearing Loss (P. Willems, ed.). Marcel Dekker, Inc. New York. pp. 269-290.
    9. Ahituv, N., Ben-David, O., Gasparini, P., and Avraham, K.B. (2004) Myosin VI in Human and Mouse Hearing Loss. In: Genetic Hearing Loss. (P. Willems, ed.). Marcel Dekker, Inc. NY. pp. 223-238.
    10. Dagan, O., and Avraham, K.B. (2004) The Complexity of Hearing Loss from a Genetics Perspective. In: Genetics, Disability, and Deafness. (J.V. Van Cleve, ed). Gallaudet University Press, Washington, D.C. pp. 81-93.
    11. Hertzano, R. and Avraham, K.B. (2005) Developmental Genes Associated with Human Hearing Loss. In: Development of the Inner Ear. (M. Kelley, D. Wu, A.N. Popper, R.R. Fay, R.R, eds). Springer-Verlag, NY. pp. 204-232.
    12. Shalit, E. and Avraham, K.B. (2007) Genetics of Hearing Loss. In: Springer Handbook of Auditory Research: Trauma, Protection and Treatment (J. Schacht, A.N. Popper, R.R. Fay, eds). Springer Publishing Co., 39:9-47.
    13. Friedman, L.M., Elkan-Miller, T., Rudnicki, A., Dror, A.A. and Avraham, K.B. (2011) MicroRNAs in the inner ear: implications for hearing loss. In: Usher Syndrome: Pathogenesis, Diagnosis and Therapy. (A. Satpel, ed). Nova Publishers. Chapter 9.