Kumar Alagramam, Ph.D.

Kumar Alagramam, Ph.D.
Associate Professor
Director of Research
Department of Otolaryngology-HNS
Case Western Reserve University


Phone : (216) 844-7261
Email : kna3@cwru.edu
Website : http://casemed.case.edu/otolaryngology/alagramam.html
 
 

RESEARCH INTERESTS

The focus of my lab is to understand the genetic basis of inner ear development, hearing and deafness, using mouse models. Since many deafness disorders in humans are associated with degeneration of the inner ear neuroepithelia, we are interested in identifying and studying mammalian genes that are involved in the development and maintenance of the neuroepithelium of the inner ear. The molecular analysis of hearing loss mutations in the mouse is an ideal way of gaining access to such genes. Current work in the lab is focused on one mouse mutation called Ames waltzer (av). The mouse av is a recessive mutation, which causes deafness and circling behavior (vestibular dysfunction) associated degeneration of hair cells in the postnatal inner ear. The gene that harbors the av mutation was identified as a protocadherin, Pcdh15 (Nat Genet. 27: 99, 2001; Hum Mol Genet. 10:1709, 2001; Hear Res. 148:181, 2000; Genetics 152:1691, 1999). Experiments are underway to understand the role of Pcdh15 in inner ear development.

Genetic, noise and drug induced loss of hair cells in the mouse and human cochlea leads to permanent hearing loss because these hair cells are not replaced. Vestibular epithelia from adult mouse show limited regenerative ability following injury, which is thought to be due to the presence of vestibular epithelial stem cells. Lack of regeneration of cochlear hair cells may be due to reduced number and/or loss of regenerative ability of stem cells in the adult cochlea. In collaboration with Robert Miller’s lab, we are looking to demonstrate the presence of cochlear stem cells in postnatal mouse organ of Corti using stem cell culture techniques and determine the conditions that would be permit the differentiation of cochlear stem cells to hair cells. These cochlear stem cells could then be transplanted into the postnatal cochlea of deaf mouse mutants, such as the av mouse, to determine if the lost hair cells could be restored.

Deaf ear Vs Normal ear

SELECTED PUBLICATIONS

  1. Zheng QY, Rozanas CR, Thalmann I, Chance MR, Alagramam KN. (2006)
    Inner ear proteomics of mouse models for deafness, a discovery strategy. Brain Res. 2006 Apr 4;
  2. Pagedar NA, Wang W, Chen DH, Davis RR, Lopez I, Wright CG, Alagramam KN. (2006)
    Gene expression analysis of distinct populations of cells isolated from mouse and human inner ear FFPE tissue using laser capture microdissection - a Technical report based on preliminary findings. Brain Res. 2006 Mar 8;
  3. Pawlowski KS, Kikkawa YS, Wright CG, Alagramam KN. (2006)
    Progression of Inner Ear Pathology in Ames Waltzer Mice and the Role of Protocadherin 15 in Hair Cell Development. J Assoc Res Otolaryngol. 2006 Jan 12; :1-12.
  4. Jones SM, Johnson KR, Yu H, Erway LC, Alagramam KN, Pollak N, Jones TA. (2005)
    A quantitative survey of gravity receptor function in mutant mouse strains. J Assoc Res Otolaryngol. 2005 Dec; 6(4):297-310.
  5. Semaan MT, Alagramam KN, Megerian CA. (2005)
    The basic science of Meniere's disease and endolymphatic hydrops. Curr Opin Otolaryngol Head Neck Surg. 2005 Oct; 13(5):301-307.
  6. Alagramam KN, Stahl JS, Jones SM, Pawlowski KS, Wright CG. (2005)
    Characterization of vestibular dysfunction in the mouse model for Usher syndrome 1F. J Assoc Res Otolaryngol. 2005 Jun; 6(2):106-118.
  7. Adato A, Michel V, Kikkawa Y, Reiners J, Alagramam KN, Weil D, Yonekawa H, Wolfrum U, El-Amraoui A, Petit C. (2005)
    Interactions in the network of Usher syndrome type 1 proteins. Hum Mol Genet. 2005 Feb 1; 14(3):347-356.
 
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