Director of Research
Dr. Kumar Alagramam earned his Masters in Biotechnology and Ph.D. in Cell and Molecular Biology from the University of Tennessee at Knoxville . He received postdoctoral training at the Oak Ridge National Laboratory, Oak Ridge, Tennessee, and Case Western Reserve University.
The long-term goal of the lab is to understand the genetic program associated with hair cell development and function in the inner ear. Dr. Alagramam has 18 years' experience in mouse genetics and molecular biology. He has considerable experience with mouse and guinea pig models of hearing loss, especially with the mouse model for deafness in Ushers. His work led to the discovery of protocadherin 15 (Pcdh15) and its association with deafness in mice and humans in 2001. From 2002-06, he reported on the identification of mouse mutants carrying different alleles of Pcdh15, and the detailed analysis of hair cells from these alleles demonstrated that mutation in Pcdh15 affects hair bundle morphology and polarity. The current focus of Dr. Alagramam's lab is to understand the precise role of Pcdh15 in hair bundle morphogenesis and mechanotransduction.
More recently (2007-present), he also focused on a mouse model for deafness in Usher 3A, which is caused by a mutation in the human clarin-1 gene. Dr. Alagramam's lab was the first to characterize a mouse model for inner ear dysfunction in Usher 3A that showed how mutation in clarin-1 affects hair cell morphology and function. However, the function of clarin-1, a four-transmembrane protein, in hair cells is unknown.
2003-Present: Director of Research, Otolaryngology
2003-Present: Co-founder and organizer “The Mouse as Instrument of Ear Research” workshop at the Jackson Laboratory, Bar Harbor, ME
2008-Present: The Maniglia Endowed Chair for Research and Education, Otolaryngology
June 2011: Awarded Tenure
July 2011-June 2015: Permanent member of the Auditory Study Section, NIDCD
Melki SJ, Yiping L, Semaan MT, Zheng, QY, Megerian CA, Alagramam KN. A mouse model validates the utility of electrocochleography in verifying endolymphatic hydrops. JARO (in press, January 2014)
Antonellis PJ, Pollock LM, Chou SW, Hassan A, Geng R, Chen X, Fuchs E, Alagramam KN, Auer M, McDermott BM Jr. ACF7 Is a Hair-Bundle Antecedent, Positioned to Integrate Cuticular Plate Actin and Somatic Tubulin. J Neurosci. 2014 Jan 1;34(1):305-12, 2014.
Au A, Stuyt JG, Chen D, Alagramam KN. Ups and downs of viagra: revisiting ototoxicity in the mouse model. PLoS One. Nov 14;8(11):e79226. doi: 10.1371/journal.pone.0079226, 2013.
Gerka-Stuyt J, Au A, Peachey NS, Alagramam KN. Transient receptor potential melastatin 1: a hair cell transduction channel candidate. PLoS One. Oct 11;8(10):e77213. doi: 10.1371/journal.pone.0077213, 2013.
Geng, R., Sotomayor, M., Kinder, K., Gopal, S.R., Gerka-Stuyt, J., Chen, D., Hardisty-Hughes, R., Ball, G., Parker, A., Gaudet, R., Furness, D., Brown, S.D.M., Corey, D.P., Alagramam, K.N. Noddy, a mouse harboring a missense mutation in protocadherin-15, reveals the impact of disrupting a critical interaction site between tip-link cadherins in inner ear hair cells. J. Neurosci. March 6;33(10):4395-4404, 2013.
Geng, R., Melki, S., Chen, D., Tian, T., Furness, D., Oshima-Takago, T., Neef, J., Moser, T., Askew, C.,Horwitz, G., Holt, J., Imanishi, Y., Alagramam, K.N. The Mechanosensory Structure of the Hair Cell Requires Clarin-1, a Protein Encoded by Usher Syndrome III Causative Gene. J. Neurosci. 32(28):9485-9498, 2012
Alagramam, K. N, Goodyear, R.J., Geng, R., Furness, D.N., van Aken, A., Walter Marcotti, M., Kros, C.J., and Richardson, G. R. Mutations in Protocadherin 15 and Cadherin 23 Affect Tip Links and Mechanotransduction in Mammalian Sensory Hair Cells. PLoS One. 6(4):e19183, 2011.
Chance MR, Chang J, Liu S, Gokulrangan G, Chen DH, Lindsay A, Geng R, Zheng QY, Alagramam K. N. Proteomics, bioinformatics and targeted gene expression analysis reveals up-regulation of cochlin and identifies other potential biomarkers in the mouse model for deafness in usher syndrome type 1F. Hum Mol Genet. 19(8):1515-27, 2010.
Melki, S.J., Heddon, C., Momin, S., Levitt, A., Frankel, J., Alagramam, K.N, Megerian, C.A. Pharmacological Protection of Hearing Loss in the Mouse Model of Endolymphatic Hydrops. Laryngoscope.120(8):1637-45, 2010.
Momin SR, Melki SJ, Alagramam K.N., Megerian CA. Spiral ganglion loss outpaces inner hair cell loss in endolymphatic hydrops. Laryngoscope. 120(1):159-65, 2010.
Surgical induction of endolymphatic hydrops by obliteration of the endolymphatic duct. Megerian CA, Heddon C, Melki S, Momin S, Paulsey J, Obokhare J, Alagramam K. N. J Vis Exp. 22;(35). pii: 1728, 2010.
Tian G, Zhou Y, Hajkova D, Miyagi M, Dinculescu A, Hauswirth WW, Palczewski K, Geng R, Alagramam K.N., Isosomppi J, Sankila EM, Flannery JG, Imanishi Y. Clarin-1, encoded by the Usher syndrome III causative gene, forms a membranous microdomain: Possible role of Clarin-1 in organizing the actin cytoskeleton. J Biol Chem, 284(28):18980-93, 2009.
Geng, R., Geller, S., Hayashi, T., Ray, C.A., Reh, T.A., Bermingham-McDonogh, O., Jones, S.M., Wright, C.G., Melki, S., Imanishi, Y, Palczewski, P. Alagramam, K.N.*, Flannery, J.G.1Usher Syndrome IIIA Gene Clarin-1 is Essential for Hair Cell Function and Associated Neural Activation. Hum. Mol. Genet. 18(15):2748-60, 2009. *Corresponding author.
Kikkawa, Y.S.,Pawlowski, K. S., Wright, C.G., Alagramam, K. N. Development of Outer Hair Cells in Normal and AmesWaltzer Mice: Cuticular Plate and Associated Structures. J. Anat. Rec. 291(2):224-32, 2008.
Megerian CA, Semaan MT, Aftab S, Kisley LB, Zheng QY, Pawlowski KS, Wright CG, Alagramam KN. A mouse model with postnatal endolymphatic hydrops and hearing loss. Hear Res. 237(1-2):90-105, 2008.
Yerukhimovich MV, Bai L, Chen DH, Miller RH, Alagramam KN.Identification and characterization of mouse cochlear stem cells. Dev Neurosci. 29(3):251-60. Epub 2006 Oct 17.
Zheng, QY., H. Yu, J.L. Washington III, L.B. Kisley, K. S. Pawlowski,C.G. Wright, K.N. Alagramam. A New Spontaneous Mutation in the Mouse Pcdh15 Gene. Hear Res, 219(1-2):110-20, 2006.
Pawlowski, K. P., C.G. Wright, and K.N. Alagramam. Progression of inner ear pathology in Ames waltzer mice and the role of protocadherin 15 in hair cell development. JARO 7(2):83-94, 2006.
Alagramam, K.N.,et al. Characterization of Vestibular Dysfunction In The Mouse Model For Usher Syndrome 1F. JARO, 6(2):106-18, 2005.
Adato A, El-Amraoui A, Kikkawa Y, Alagramam K.N., Weil D, Yonekawa H, El-Amraoui A, Petit C. Interactions in the Usher syndrome type 1 (USH1) proteins network. Hum Mol Genet 14(3):347-356, 2005.
Alagramam KN, Yuan H, Kuehn MH, Murcia CL, Wayne S, Srisailpathy CR, Lowry RB, Knaus R, Van Laer L, Bernier FP, Schwartz S, Lee C, Morton CC, Mullins RF, Ramesh A, Van Camp G, Hageman GS, Woychik RP, Smith RJ. Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. Hum Mol Genet. 10(16):1709-18, 2001
Alagramam KN, Murcia CL, Kwon HY, Pawlowski KS, Wright CG, Woychik RP. The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene. Nat Genet. 27(1):99-102, 2001
Alagramam K, Naider F, Becker JM. A recognition component of the ubiquitin system is required for peptide transport in Saccharomyces cerevisiae. Mol Microbiol. 15(2):225-34. 1995