Bechara Kachar, M.D.

Chief
Section on Cell Structure
Laboratory of Cellular Biology

Research Statement

The Section on Cell Structure uses advanced microscopy imaging in combination with molecular and cell biology techniques to study mechano-sensory transduction in auditory and vestibular sensory organs.

Lab Personnel

Aurea de Sousa, Ph.D., Research Fellow(Send e-mail)
Hirofume Sakaguchi, M.D., Ph.D., Visiting Fellow(Send e-mail)
Felipe Salles, DDS, Ph.D., Visiting Fellow(Send e-mail)
Takashi Sato, M.D., Ph.D., Visiting Fellow(Send e-mail)
Raymond Merritt, University of Maryland Grad. Student(Send e-mail)
Uri Manor, Johns Hopkins Univ. Grad. Student(Send e-mail)
Joshua Tokita, Grad. Student(Send e-mail)
Mark E. Schneider, Ph.D., Staff scientist (Send e-mail)

Resources for Scientists

• Mouse organ of Corti cDNA library and EST database

Selected Publications

• Nunes FD, Lopez LN, Lin HW, Davies C, Azevedo RB, Gow A, Kachar B. Distinct subdomain organization and molecular composition of a tight junction with adherens junction features. J Cell Sci. 2006 Dec 1;119(Pt 23):4819-27.
• Silva, H. S., Martins, M. L. ,  Vilela, M. J. , Jaeger, R. and Kachar B. 1/f ruffle oscillations in plasma membranes of amphibian epithelial cells under normal and inverted gravitational orientations. Phys. Rev. E 74, 041903, 2006.
• Schneider ME, Dose AC, Salles FT, Chang W, Erickson FL, Burnside B, Kachar B. A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression. J Neurosci. 26(40):10243-52, 2006.
• Ricci AJ, Kachar B, Gale J, Van Netten SM. Mechano-electrical transduction: new insights into old ideas. J Membr Biol. 209(2-3):71-88, 2006.
• Grati M, Schneider ME, Lipkow K, Strehler EE, Wenthold RJ, Kachar B. Rapid turnover of stereocilia membrane proteins: evidence from the trafficking and mobility of plasma membrane Ca(2+)-ATPase 2. J Neurosci.  26(23):6386-95, 2006.
• Beisel KW, Rocha-Sanchez SM, Morris KA, Nie L, Feng F, Kachar B, Yamoah EN, Fritzsch B. Differential expression of KCNQ4 in inner hair cells and sensory neurons is the basis of progressive high-frequency hearing loss. J Neurosci. 25(40):9285-93, 2005.
• Rzadzinska A, Schneider M, Noben-Trauth K, Bartles JR, Kachar B. Balanced levels of Espin are critical for stereociliary growth and length maintenance. Cell Motil Cytoskeleton. 62(3):157-65, 2005.
• Dougherty GW, Adler HJ, Rzadzinska A, Gimona M, Tomita Y, Lattig MC, Merritt RC Jr, Kachar B. CLAMP, a novel microtubule-associated protein with EB-type calponin homology. Cell Motil Cytoskeleton. 62(3):141-56. Erratum in: Cell Motil Cytoskeleton. 2005 Dec;62(4):259, 2005.
• Gillespie PG, Dumont RA, Kachar B. Have we found the tip link, transduction channel, and gating spring of the hair cell? Current Opinion in Neurobiology 15(4):389–96, 2005.
• Di Pasquale G, Rzadzinska A, Schneider ME, Bossis I, Chiorini JA, Kachar B. A novel bovine virus efficiently transduces inner ear neuroepithelial cells. Molecular Therapy 11(6):849–55, 2005.
• Morris KA, Snir E, Pompeia C, Koroleva IV, Kachar B, Hayashizaki Y, Carninci P, Soares MB, Beisel KW. Differential expression of genes within the cochlea as defined by a custom mouse inner ear microarray. Journal of the Association for Research in Otolaryngology 6(1):75–89, 2005.
• Lin HW, Schneider ME, Kachar B. When size matters: the dynamic regulation of stereocilia lengths. Current Opinion in Cell Biology 17(1):55–61, 2005.
• Kong XT, Deng FM, Hu P, Liang FX, Zhou G, Auerbach AB, Genieser N, Nelson PK, Robbins ES, Shapiro E, Kachar B, Sun TT. Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases. The Journal of Cell Biology 20;167(6):1195–204, 2004.
• Shoelson B, Dimitriadis EK, Cai H, Kachar B, Chadwick RS. Evidence and implications of inhomogeneity in tectorial membrane elasticity. Biophysical Journal 87(4):2768–77, 2004.
• Gow A, Davies C, Southwood CM, Frolenkov G, Chrustowski M, Ng L, Yamauchi D, Marcus DC, Kachar B. Deafness in Claudin 11-null mice reveals the critical contribution of basal cell tight junctions to stria vascularis function. The Journal of Neuroscience 24(32):7051–62, 2004.
• Beisel KW, Shiraki T, Morris KA, Pompeia C, Kachar B, Arakawa T, Bono H, Kawai J, Hayashizaki Y, Carninci P. Identification of unique transcripts from a mouse full-length, subtracted inner ear cDNA library. Genomics 83(6):1012–23, 2004.
• Pompeia C, Hurle B, Belyantseva IA, Noben-Trauth K, Beisel K, Gao J, Buchoff P, Wistow G, Kachar B. Gene expression profile of the mouse organ of Corti at the onset of hearing. Genomics 83(6):1000–11, 2004.
• Rzadzinska AK, Schneider ME, Davies C, Riordan GP, Kachar B. An actin molecular treadmill and myosins maintain stereocilia functional architecture and self-renewal. The Journal of Cell Biology 164(6):887–97, 2004.
• Royaux IE, Belyantseva IA, Wu T, Kachar B, Everett LA, Marcus DC, Green ED. Localization and functional studies of pendrin in the mouse inner ear provide insight about the etiology of deafness in pendred syndrome. Journal of the Association for Research in Otolaryngology 4(3):394–404, 2003.
• Adler HJ, Belyantseva IA, Merritt RC Jr, Frolenkov GI, Dougherty GW, Kachar B. Expression of prestin, a membrane motor protein, in the mammalian auditory and vestibular periphery. Hearing Research 184(1–2):27–40, 2003.
• Frolenkov GI, Mammano F, Kachar B. Regulation of outer hair cell cytoskeletal stiffness by intracellular Ca2+: underlying mechanism and implications for cochlear mechanics. Cell Calcium 33(3):185–95, 2003.
• Schneider M.E, Belyantseva IA, Azevedo R.B, Kachar B. Stuctural Cell Biology: Rapid Renewal of Auditory Hair Bundles. Nature 20(24):837–838, 2002.
• Belyantseva IA, Adler H, Cury R, Frolenkov G, Kachar B. Expression and localization of prestin and sugar transporter GLUT-5 during development of electromotility in cochlear outer hair cells. The Journal of Neuroscience 20(24):RC116, 2000.
• Belyantseva IA, Frolenkov G, Wade J, Mammano F, Kachar B. Water permeability of cochlear outer hair cells: characterization and relationship to electromotility. The Journal of Neuroscience 20(24):8996–9003, 2000.
• Frolenkov GL, Mammano F, Kachar B. Action of 2,3-butanedione monoxime on the voltage-dependent length change and capacitance of outer hair cells from the guinea pig cochlea. The Journal of Physiology 531:667–676, 2001.
• Frolenkov G, Mammano F, Belyantseva I, Coling D, Kachar B. Two distinct Ca(2+)-dependent signaling pathways regulate the motor output of cochlear outer hair cells. The Journal of Neuroscience 15:5940–5948, 2000.
• Kachar B, Parakkal M, Kurc M, Zhao Y, Gillespie P. High-resolution structure of hair-cell tip links. PNAS 97:13336–13341, 2000.
• Azzam N, Hallenbeck J, Kachar B. Membrane changes during hibernation. Organelle lipids undergo rapid reversible rearrangements as body temperature drops. Nature 21;407(6802):317–318, 2000.
• Dumont RA, Lins U, Filoteo AG, Penniston J, Kachar B, Gillespie P. Plasma membrane Ca2+-ATPase isoform 2a is the PMCA of hair bundles. The Journal of Neuroscience 21(14):5066–5078, 2001.
• Lins U, Farina M, Kurc M, Riordan R, Thalmann R, Thalmann I, Kachar B. The otoconia of the guinea pig utricle: internal structure, surface exposure, and interactions with the filament matrix. Journal of Structural Biology 131:67–78, 2000.
• Wilcox ER, Burton QL, Naz S, Riazuddin S, Smith TN, Belyantseva I, Ben-Yosef T, Liburd NA, Morell RJ, Kachar B, Wu DK, Griffith AJ, Riazuddin S, Friedman TB. Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Cell 104:165–172, 2001.
• Lagostena L, Ashmore JF, Kachar B, Mammano F. Purinergic control of intracellular calcium and gap junction communication in supporting Hensen's cells of the guinea pig cochlea. The Journal of Physiology 531(3):693–706, 2001.
• Dipalma F, Holme R, Bryda EC, Belyantseva IA, Pellegrino R, Kachar B, Steel KP, Noben-Trauth K. Mutations in cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for usher syndrome type 1D. Nature Genetics 27(1):103–107, 2001.
• Anderson* DW, Probst* FJ, Belyantseva* I, Fridell RA, Beyer L, Martin DM, Kachar B, Friedman TF, Raphael Y, Camper SA. The motor and tail regions of myosin XV are critical for normal structure and function of auditory and vestibular hair cells. Human Molecular Genetics 22;9(12):1729–1738, 2000. (*authors contributed equally)
• Everett LA, Belyantseva IA, Noben-Trauth K, Cantos R, Chen A, Thakkar S, Hoogstraten-Miller S, Kachar B, Wu D, Green E. Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome. Human Molecular Genetics 10(2):153–161, 2001.
• Davies C, Petralia R, Tingley D, Kachar B, Wenthold R. Distribution of members of the PSD-95 family of MAGUK proteins at the synaptic region of inner and outer hair cells of the guinea pig cochlea. Synapse 40(4):258–68, 2001.
• Hu P, Deng F, Liang F, Hu C, Auerbach A, Shapiro E, Wu X, Kachar B, Sun H. Ablation of uroplakin III gene results in small urothelial plaques, urothelial leakage, and vesicoureteral reflux. The Journal of Cell Biology 151:961–971, 2000.
• Mammano F, Frolenkov G, Lagostena L, Belyantseva I, Kurc M, Dodane V, Colavita A, Kachar B. ATP-induced Ca(2+) release in cochlear outer hair cells: localization of an inositol triphosphate-gated Ca(2+) store to the base of the sensory hair bundle. The Journal of Neuroscience 19:6918–6929, 1999.
• Frolenkov GI, Atzori M, Kalinec F, Mammano F, Kachar B. The membrane based mechanism of cell motility in the cochlear outer hair cells. Molecular Biology of the Cell 9:1961–1968, 1998.
• Espreafico E, Coling D, Tsakraklides V, Krogh K, Wolenski JS, Kalinec G, Kachar B. Localization of myosin-V in the centrosome. PNAS 95:8636–8641, 1998.
• Kachar B, Liang F, Lins U, Ding M, Wu XR, Stoffler D, Aebi U, Sun TT. Three-dimensional analysis of the 16-nm urothelial plaque particle: luminal surface exposure, preferential head-to-head interaction, and dynamic plaque/hinge formation. Journal of Molecular Biology 285:595–608, 1999.
• Gow A, Southwood CM, Li J, Pariali M, Riordan G, Bronstein J, Brodie S, Kachar B, Lazarini R. CNS myelin and sertoli cell tight junction strands are absent in Osp/Claudin 11- null mice. Cell 99:649–659, 1999.
• Liang Y, Wang A, Belyantseva I, Anderson DW, Probst FJ, Barber T, Miller W, Touchman JW, Jin L, Sullivan SL, Sellers JR, Camper SA, Kachar B, Friedman TB, Fridell RA. Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2. Genomics 61:243–258, 1999.
• Frolenkov GI, Belyantseva IA, Kurc M, Mastroianni MA, Kachar B. Cochlear outer hair cell electromotility can provide force for both low and high intensity distortion product otoacoustic emissions. Hearing Research 126(1–2):67–74, 1998.
• Kurc M, Dodane V, Pinto D, Kachar B. Presynaptic localization of G protein isoforms in the efferent nerve terminals of the mammalian cochlea. Hearing Research 116:1–9, 1998.
• Farshori P, Kachar B. Redistribution and phosphorylation of occludin during opening and resealing of tight junctions in cultured epithelial cells. The Journal of Membrane Biology 170:147–156, 1999.
• Kalinec F, Kalinec G, Boukhvalova M, Kachar B. Establishment and characterization of conditionally immortalized organ of corti cell lines. Cell Biology International 23:175–184, 1999.
• Liang F, Kachar B, Ding M, Zhai Z, Wu XR, Sun TT. Urothelial hinge as a highly specialized membrane: detergent-insolubility, urohingin association, and in vitro formation. Differentiation 65:59–69, 1999.
• Kurc M, Farina M, Lins U, Kachar B. Structural basis for mechanical transduction in the frog vestibular sensory apparatus: III. The organization of the otoconial mass. Hearing Research 131:11–21, 1999.
• Lacaz-Vieira F, Jaeger MM, Farshori P, Kachar B. Small synthetic peptides homologous to segments of the first external loop of occludin impair tight junction resealing. The Journal of Membrane Biology 168:289–297, 1999.

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