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      Matthew W. Kelley, Ph.D.


SECTION ON DEVELOPMENTAL NEUROSCIENCE
      
            NIHBC 35A - PNRC II BG RM 1D-993 35A CONVENT DR BETHESDA MD 20892
      
Phone:
      +1 301 435 8075

Fax:
      +1 301 480 3001

Email:
      kelleymt@nidcd.nih.gov

            photo of Matthew Kelly

**Chief, Laboratory of Cochlear Development****Chief, Section on Developmental Neuroscience**

Dr. Kelley received his B.A. from Cornell University and his Ph.D. from the University of Virginia. Following a post-doctoral fellowship at the University of Washington, he became an Assistant Professor in the Department of Cell Biology at Georgetown University in 1996. In 2000 he moved to the NIDCD, first as Acting Chief and then (since 2004) as Chief of the section on Developmental Neuroscience. Dr. Kelley's laboratory works on the cellular and molecular development of the mammalian cochlea.
      
Laboratory:
      Laboratory of Cochlear Development

  Scientific Areas:
          Development of the mammalian cochlea
**Selected Publications**Sherrill, H.E., Jean, P., Driver, E.C., Sanders, T.R., Fitzgerald, T.S., Moser, T., Kelley, M.W. (2019) Pou4f1 defines a subgroup of type I spiral ganglion neurons and is necessary for normal inner hair cell presynaptic Ca2+ signaling. *J Neurosci*. 2019 Jul 3;39(27):5284-5298. Epub 2019 May 13. doi: 10.1523/JNEUROSCI.2728-18.2019.McInturff, S., Burns, J.C., Kelley, M.W. (2018) Characterization of spatial and temporal development of Type I and Type II hair cells in the mouseutricle using new cell-type-specific markers. *Biol Open*. 2018 Nov 19;7(11). pii: bio038083. doi: 10.1242/bio.038083Mays, J.C., Kelly, M.C., Coon, S.L., Holtzclaw, L., Rath, M.F., Kelley, M.W., Klein, D.C. (2018) Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypesand cell type-specific daily patterns of gene expression. *PLoS One*. 2018 Oct 22;13(10):e0205883. doi: 10.1371/journal.pone.0205883. eCollection 2018.Driver, E.C., Northrop, A., Kelley, M.W. (2017) Cell migration, intercalation and growth regulate mammalian cochlear extension. *Development*. Oct 15;144(20):3766-3776. doi: 10.1242/dev.151761. Epub 2017 Sep 4.Puligilla, C., Kelley, M.W. (2017) Dual role for Sox2 in specification of sensory competence and regulation of Atoh1 function. *Dev Neurobiol*.  Jan;77(1):3-13. doi: 10.1002/dneu.22401. Epub 2016 Jun 6.Burns, J.C., Kelly, M.C., Hoa, M., Morell, R.J., and Kelley, M.W.  (2015) Single-cell RNA-Seq resolves cellular complexity in inner ear sensory organs. *Nature Communications*, 6:8557.Coate, T.M., Isgrig, K.T., Spita, N.A., and Kelley, M.W.  (2015) Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons. *eLife*, 10:7554.Haque, K.D., Pandey, A.K., Kelley, M.W., and Puligilla, C. (2015) Culture of embryonic mouse cochlear explants and gene transfer by electroporation. *JOVE*, 95:52260.Mann, Z.F., Thiede, B., Chang, W., Shin, J.-B., May-Simera, H.L., Lovett, M., Corwin, J.T., and Kelley, M.W.  (2014) A gradient of Bmp7 specifies the tonotopic axis in the developing inner ear.  *Nature Communications*, 5:3839.Thiede, B., Mann, Z.F., Chang,W., Ku, Y.-C., Son, Y.K., Lovett, M., Kelley, M.W., and Corwin, J. T. (2014) Retinoic acid signaling regulates the development of tonotopically patterned hair cells in the chicken cochlea. *Nature Communications*, 5:3840.Mann, Z.F and Kelley, M.W. (2014) Development of the inner ear. In: *Principles of Developmental Genetics, 2nd Edition*, Associated Press.  377-392.Raft, S., Coate, T.M., Kelley, M.W., Crenshaw, E.B., and Wu, D.K. (2014) Pou3f4-mediated regulation of ephrin-B2 controls temporal bone development in the mouse. *PLOS ONE*, 9(10):e109043.May-Simera, H.M., Petralia, R.S., Montcouquiol, M., Wang, Y.-X., Szarama, K.B., Liu, Y., Lin, W., Deans, M.R., Pazour, G.J. and Kelley, M.W. (2014) Ciliary proteins Bbs8 and Ift20 promote planar cell polarity in the cochlea. *Development,*142:555-566.Okano, T. and Kelley, M.W. (2013) Expression of insulin-like growth factor binding proteins during mouse cochlear development. *Developmental Dynamics*, 242:1210-1221.Kelley, M.W.  (2013) Taking hair cell regeneration up a notch. *The Hearing Journal,* 66:2.Kelley, M.W.  (2013) Signaling pathways and commitment to cell fate. *Molecular Signaling in Mammalian Inner Ear Development*. Nova Publishers.133-154.Mann, Z.F., Chang, W., Lee, K.Y., King, K.A., and Kelley, M.W. (2013) Expression and function of scleraxis in the developing auditory system. *PLOS One*, 8:e75521.Ng, L., Kelley, M.W., and Forrest, D. (2013) Making sense with thyroid hormone—the role of T(3) in auditory development. *Nature Reviews Endocrinology,*9:296-307.Coate, T.M. and Kelley, M.W. (2013) Making connections in the inner ear: recent insights into the development of spiral ganglion neurons and their connectivity with sensory hair cells.  *Seminars in Cell and Developmental Biology*, 24:460-469.Cui, C., Bishwanath, C. Zhang, Z., Francis, R.J., Yagi, H. Antosnewski, L.M., SanAugustin, J.T., Francis, D. Yu, Q, Puligilla, C., Kelley, M.W., Hukriede, N.A., Pazour, G.J, and Lo, C.W. (2013)  Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton. *PLOS Biology*, 11:e1001720.Coate, T.M., Raft, S., Zhao, X., Ryan, A.K., Crenshaw, E.B., and Kelley, M.W. (2012) Otic mesenchyme cells regulate the fasciculation of spiral ganglion neurons through a Pou3f4/EphA4 signaling pathway. *Neuron*73:49-63.Rachel, R.A., May-Simera, H.L., Veleri, S., Gotoh, N., Choi, B.Y., Murga-Zamalloa, C., McIntyre, J., Marek, J., Lopez, I., den Hollander, A., Fariss, R.N., Beales, P.L., Li, T., Jacobson, S.G., Martens, J., Friedman, T.B., Khanna, H., Koenekoop, R.K., Kelley, M.W., and Swaroop, A. (2012) Combining *Cep290* and *Mkks* ciliopathy alleles in mice rescues sensory defects and restores ciliogenesis. *J. Clinical Investigation* 122:1233-1245.May-Simera, H. and Kelley, M.W. (2012) Examining planar cell polarity in the mammalian cochlea. *Planar Cell Polarity: Methods and Protocols*, Spring Publishing. 39:157-171.Wu, D.K. and Kelley, M.W. (2012) Molecular mechanisms of inner ear development. In:  Mammalian Development, *Cold Spring Harbor Perspectives*.May-Simera, H.M. and Kelley, M.W. (2012) Planar cell polarity in the inner ear. *Current Topics in Developmental Biology*, 101:109-137.Szarama, K.B., Gavara, N., Petralia, R.S., Kelley, M.W., and Chadwick, R.S. (2012)  Cytoskeletal changes in actin and microtubules underlie the developing mechanical properties of sensory and supporting cells in the mouse cochlea. *Development* 139:2187-2197.Jacques, B.E., Dabdoub, A., and Kelley, M.W. (2012) Fgf signaling regulates development and transdifferentiation of hair cells and support cells in the basilar papilla.  *Hearing Research*  289:27-39.May-Simera, H.M. and Kelley, M.W. (2012) Cilia, Wnt signaling, and the cytoskeleton. *Cilia* 1:7.Okano, T. and Kelley, M.W. (2012) Restoration of hearing; a potential role for stem cells? *Trends in Amplification*.16:4-18.Jacques, B.E., Puligilla, C., Weichert, R.M., Ferrer-Vaquer, A., Hadjantonakis, A.-J., Kelley, M.W., and Dabdoub, A. (2012) A dual function for canonical Wnt/b-catenin signaling in the developing mammalian cochlea. *Development*  139:4395-4404.Szarama, K.B., Gavara, N., Petralia, R.S., Chadwick, R.S., and Kelley, M.W. (2012) Thyroid hormone increases Fgfr activity and disrupts cell mechanics in the developing organ of Corti.  *BMC Developmental Biology*, 13:6.Driver, E.C., Sillers, L., Coate, T.M., Rose, M., and Kelley, M.W. (2012) The Atoh1 lineage gives rise to hair cells and supporting cells within the mammalian cochlea. *Developmental Biology,*376:86-98.Okano, T., Xuan, S.,  and Kelley, M.W. (2011) Insulin-like growth factor regulates the timing of sensory cell differentiation in the mouse cochlea. *J. Neuroscience*31:18104-18118.Tadenev, A., Kulaga, H., May-Simera, H.M., Kelley, M.W., Katsanis, N. and Reed, R. (2011) Loss of Bardet-Biedl syndrome protein-8 (BBS8) perturbs olfactory function, protein localization and axon targeting. *P.N.A.S.* 108:10320-10325.Mann, Z.F. and Kelley, M.W. (2011) Development of tonotopy in the auditory periphery. *Hearing Research*  276:2-15.Yamamoto, N., Chang, W., and Kelley, M.W. (2011) Rpbj regulates development of prosensory development in the mammalian cochlea. *Developmental Biology*, 353:367-379.Stottmann, R., Moran, J., Turbe-Doan, A., Driver, E.C., Kelley, M.W., and Beier, D.R. (2011)  Focusing forward genetics: A tri-partite ENU screen for neurodevelopmental mutations in the mouse. *Genetics*, 188:615-624.Hertzano, R., Puligilla, C., Chan, A., Timothy, C., Depireux, D., Ahmed, Z., Friedman, T.B., Riazuddin, S., Kelley, M.W. and Strome, S.E.  (2010) CD44 is a marker for the outer pillar cell in the mouse inner ear. *JARO*, 11:407-418.Driver EC, Kelley MW. Transfection of mouse cochlear explants by electroporation. *Curr Protoc Neurosci*. Apr;Chapter 4:Unit 4.34.1-10, 2010.Puligilla C, Dabdoub A, Brenowitz SD, Kelley MW. Sox2 induces neuronal formation in the developing mammalian cochlea.*J Neurosci*. Jan 13;30(2):714-22, 2010.Driver EC, Kelley MW. Specification of cell fate in the mammalian cochlea. *Birth Defects Res C Embryo Today*. Sep;87(3):212-21, 2009. Review.Kelley MW, Driver EC, Puligilla C. Regulation of cell fate and patterning in the developing mammalian cochlea.*Curr Opin Otolaryngol Head Neck Surg*. Oct;17(5):381-7, 2009.Puligilla C, Kelley MW. Building the world's best hearing aid; regulation of cell fate in the cochlea. *Curr Opin Genet Dev*. Aug;19(4):368-73, 2009. Epub 2009 Jul 13. Review.Yamamoto N, Okano T, Ma X, Adelstein RS, Kelley MW. Myosin II regulates extension, growth and patterning in the mammalian cochlear duct. Development. Jun;136(12):1977-86, 2009. Epub 2009 May 13.Dabdoub A, Puligilla C, Jones JM, Fritzsch B, Cheah KS, Pevny LH, Kelley MW. Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea. Proc Natl Acad Sci USA. Nov 25;105(47):18396-401, 2008. Epub 2008 Nov 14.Driver EC, Pryor SP, Hill P, Turner J, Rüther U, Biesecker LG, Griffith AJ, Kelley MW. Hedgehog signaling regulates sensory cell formation and auditory function in mice and humans. *J Neurosci.* Jul 16;28(29):7350-8, 2008.Kelley MW. Leading Wnt down a PCP path: Cthrc1 acts as a coreceptor in the Wnt-PCP pathway. *Dev Cell*. Jul;15(1):7-8, 2008.Chen Z, Montcouquiol M, Calderon R, Jenkins NA, Copeland NG, Kelley MW, Noben-Trauth K. Jxc1/Sobp, encoding a nuclear zinc finger protein, is critical for cochlear growth, cell fate, and patterning of the organ of corti.*J Neurosci.* Jun 25;28(26):6633-41, 2008.Kelley MW. Has hair cell loss MET its match? *Proc Natl Acad Sci U S A.* 2007 Oct 16;104(42):16400-1. Epub Oct 9, 2007. No abstract available.Kelley MW. Cellular commitment and differentiation in the organ of Corti. *Int J Dev Biol*. 51(6-7):571-83, 2007. Review.Jacques BE, Montcouquiol ME, Layman EM, Lewandoski M, Kelley MW. Fgf8 induces pillar cell fate and regulates cellular patterning in the mammalian cochlea. *Development*. Aug;134(16):3021-9, 2007. Epub 2007 Jul 18.Puligilla C, Feng F, Ishikawa K, Bertuzzi S, Dabdoub A, Griffith AJ, Fritzsch B, Kelley MW. Disruption of fibroblast growth factor receptor 3 signaling results in defects in cellular differentiation, neuronal patterning, and hearing impairment. *Dev Dyn*. Jul;236(7):1905-17, 2007.Hertzano R, Dror AA, Montcouquiol M, Ahmed ZM, Ellsworth B, Camper S, Friedman TB, Kelley MW, Avraham KB. Kelley MW.Regulation of cell fate in the sensory epithelia of the inner ear. *Nat Rev Neurosci.*Nov;7(11):837-49, 2006.Montcouquiol M, Crenshaw EB 3rd, Kelley MW. Noncanonical Wnt signaling and neural polarity. Annual Review of Neuroscience 29:363–86, 2006.Montcouquiol M, Sans N, Huss D, Kach J, Dickman JD, Forge A, Rachel RA, Copeland NG, Jenkins NA, Bogani D, Murdoch J, Warchol ME, Wenthold RJ, Kelley MW. Asymmetric localization of Vangl2 and Fz3 indicate novel mechanisms for planar cell polarity in mammals. The Journal of Neuroscience 26(19):5265–75, 2006.Jones JM, Montcouquiol M, Dabdoub A, Woods C, Kelley MW. Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Corti. The Journal of Neuroscience 26(2):550–8, 2006.Dabdoub A, Kelley MW. Planar cell polarity and a potential role for a Wnt morphogen gradient in stereociliary bundle orientation in the mammalian inner ear. Journal of Neurobiology 64(4):446–57, 2005.Woods C, Montcouquiol M, Kelley MW. Math1 regulates development of the sensory epithelium in the mammalian cochlea. Nature Neuroscience 7(12):1310–8, 2004.Barald KF, Kelley MW. From placode to polarization: new tunes in inner ear development. Development 131(17):4119–30, 2004.Hertzano R, Montcouquiol M, Rashi-Elkeles S, Elkon R, Yucel R, Frankel WN, Rechavi G, Moroy T, Friedman TB, Kelley MW, Avraham KB. Transcription profiling of inner ears from Pou4f3(ddl/ddl) identifies Gfi1 as a target of the Pou4f3 deafness gene. Human Molecular Genetics 13(18):2143–53, 2004.McKenzie E, Krupin A, Kelley MW. Cellular growth and rearrangement during the development of the mammalian organ of Corti. Developmental Dynamics 229(4):802–12, 2004.Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116(6):883–95, 2004.Ng L, Goodyear RJ, Woods CA, Schneider MJ, Diamond E, Richardson GP, Kelley MW, Germain DL, Galton VA, Forrest D. Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase. Proceedings of the National Academy of Sciences of the USA 101(10):3474–9, 2004.Kelley MW. Cell adhesion molecules during inner ear and hair cell development, including notch and its ligands. Current Topics in Developmental Biology 57:321–56, 2003.Kelley MW, Lanford PJ, Jones I, Amma L, Ng L, Forrest D. Analysis of nuclear receptor function in the mouse auditory system. Methods in Enzymology 364:426–48, 2003.Montcouquiol M, Kelley MW. Planar and vertical signals control cellular differentiation and patterning in the mammalian cochlea. The Journal of Neuroscience 23(28):9469–78, 2003.Kelley MW. Exposing the roots of hair cell regeneration in the ear. Nature Medicine 9(10):1257–9, 2003.Kelley MW. Determination and commitment of mechanosensory hair cells. TheScientificWorldJournal 2:1079–94, 2002.Montcouquiol, M., Rachel, R.A., Lanford, P.J., Copeland, N.G., Jenkins, N.A., and Kelley, M.W. Identification of *Vangl2* and *Scrb1* as planar polarity genes in mammals. Nature 423:173–176, 2003.Daboub, A., Donohue, M.J., Brennan, A., Wolf, V., Montcouquiol, M., Sasson, D.A., Hseih, J.-C., Rubin, J.S., Salinas, P.C. and Kelley, M.W. Wnt Signaling Mediates Reorientation of Outer Hair Cell Stereociliary Bundles in the Mammalian Cochlea. Development 130:2375–2384, 2003.Mueller, K.L., Jacques, B.E. and Kelley, M.W. (2002) FGF signaling regulates pillar cell development in the organ of Corti. The Journal of Neuroscience 22:9368–9377.Griffith AJ, Szymko YM, Kaneshige M, Quinonez R, Kaneshige K, Mastroianni MA, Kelley MW, Cheng S. Knock-in mouse model for resistance to thyroid hormone (RTH): An RTH mutation in the thyroid hormone receptor beta gene disrupts cochlear morphogenesis. Journal of the Association for Research in Otolaryngology 3(3):279–288, 2002.Rüsch A, Ng L, Goodyear R, Oliver D, Lisoukov I, Vennström B, Richardson G, Kelley MW, Forrest D. Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors. The Journal of Neuroscience 21:9792–9800, 2001.Angel Campos-Barros A, Amma LL, Wang Z, Shailam R, Kelley MW, Forrest D. Type 2 iodothyronine deiodinase expression in the cochlea preceding the onset of hearing. Proceedings of the National Academy of Sciences of the USA 97:1287–1292, 2000.Lanford PJ, Shailam R, Norton CR, Gridley T, Kelley MW. Expression of *Math1* and *HES5* in the cochleae of wildtype and Jag2 mutant mice. JARO 1:161–170, 2000.Zhang N, Martin GV, Kelley MW, Gridley T. A mutation in the lunatic fringe gene suppresses the effects of a Jagged2 mutation on inner hair cell development in the cochlea. Currents in Biology 10:659–662, 2000.
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