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Pharmacological & Physiological Science
Room M 362 || 1402 South Grand Blvd
St. Louis, Missouri 63104
Michael Anne Gratton, Ph.D.
1) Matrix Otopathology: .Alport syndrome is a genetic basement membrane disease of the kidney, ear and eye. We use the mouse model of Alport syndrome to study basement membrane function in the adult inner ear. In the Alport mouse, the basement membranes surrounding blood vessels of the stria vascularis, a tissue in the inner ear become grossly thickened. The expression of genes and proteins controlling basement membrane synthesis and degradation are being quantified in the Alport mouse while cationic probes are being used to determine if blood vessel permeability has been altered. The electrochemical and transport properties of the Alport stria following noise exposure to deplete strial energy production are being explored.
2) Potassium Homeostasis: A unique transmembrane potential, the endocochlear potential (EP), is required for normal sound transduction. The mechanisms generating and maintaining this inner ear potential have not been entirely elucidated. In collaboration with Ebenezer Yamoah at UC-Davis, we seek to characterize the specific functions of recently identified K+ and Cl- channels, and determine how they work together to mediate the EP. My role to localize channel proteins in inner ear tissues using imunohistochemistry at the cellular and subcellular level.
3) Gene therapy for Usher Syndrome 1C: The longterm goal of this research is to develop gene therapy approaches that can be used successfully in vivo to slow or prevent deafness and blindness in Usher Syndrome. In collaboration with Jean Bennett, University of Pennsylvania, we use a retroviral package to deliver genes to the developing cochlea. The therapeutic effects of the wildtype harmonin gene in the neonatal pupare assessed in structure/function studies.
1970-71 Dean's List, University of Wisconsin
1988 Dissertation Award, Diamond Fund, SUNY at Buffalo
1989-90 PFP Fellow Award, Univ. of Texas Southwestern Medical Center
1 R01 DC006442-01 Matrix Otopathology 01/1/04-8/31/12 NIH-NIDCD Michael Anne Gratton, PI
This research examines the role of basement membranes in homeostasis of the cochlea and in particular, those of the capillaries of the stria vascularis.
|1984-87||University of Texas at Dallas Graduate Assistantship|
|1989||New Investigator Award, American Speech-Language-Hearing Foundation|
|1992||Member, Special Review Panel, NIDCD, NIH|
|1999-2001||Member, Scientific Review Committee, Deafness Research Foundation|
|2001||Member, Research Task Force, Deafness Research Foundation|
|2002||Visiting Scientist, Biocurrents Research Center, Marine Biology Laboratory, Woods Hole, MA|
|2003||Member, Institute of Aging, University of Pennsylvania|
|2004||Member, Mahoney Institute of Neurological Sciences, University of Pennsylvania|
|2006||Member, Special Review Panel, NIDCD, NIH|
|2007||Member, Special Review Panel, NIA, NIH|
|2008||Member, Special Review Panel, NIA, NIH|
1. Arehole S. Salvi RJ, Saunders SS, Gratton MA. Evoked-response forward-masking functions in chinchillas with noise-induced permanent hearing loss. Audiol 1989; 28:92-110.
2. Boettcher FA, Henderson D, Gratton, MA, Byrne C, Bancroft B. Recent advances in the understanding of noise interactions. Arch Compl Environ Studies 1989;1:15-21.
3. Fiorino F, Gratton MA, Subbana M, Bianchi L, Henderson D. Physiological mechanisms underlying progressive resistance to noise-induced hearing loss. II Valsalva 1989;54 (Suppl 1):36-41.
4. Gratton MA, Salvi RJ, Kamen BA, Saunders SS. Interaction of cisplatin and noise in the peripheral auditory system. Hear Res 1990;50:211-224.
5. Salvi RJ, Saunders SS, Gratton MA, Arehole S, Powers N. Enhanced evoked response amplitudes in the inferior colliculus of the chinchilla following acoustic trauma. Hear Res 1990;50:245-258.
6. Henderson D, Subramanian M, Gratton MA, Saunders SS. Impact noise: The importance of level, duration and repetition rate. J Acoust Soc Am 1991;89(3):1350-1357.
7. Danielson R, Henderson D, Gratton MA, Bianchi,L ,Salvi RJ. The importance of "temporal pattern" in traumatic impulse noise exposure. J Acoust Soc Am 1991;90(1): 209-218.
8. Gratton MA, Wright,CG. Hyperpigmentation of chinchilla stria vascularis following acoustic trauma. Pigment Cell Res 1992;5:30-37.
9. Gratton MA, Wright CG. Alterations of inner ear morphology in experimental hypercholesterolemia. Hear Res 1992;61:97-105.
10. Boettcher FA, Gratton MA, Schmiedt RA Effects of noise and age on the auditory system. Occup Med 1995;10(3):577-591.
11. Gratton MA, Schulte BA. Alterations in microvasculature associated with atrophy of the stria vascularis in quiet-aged gerbils. Hear Res 1995;82:44-52.
12. Gratton MA, Smyth BJ, Schulte BA, Vincent DA. Na,K-ATPase activity decreases in the cochlear lateral wall of quiet-aged gerbils. Hear Res 1995;83:43-50.
13. Vincent DA, Gratton MA, Smyth BJ, Schulte BA. Effect of post-mortem autolysis on Na,K-ATPase activity and antigenicity in the gerbil cochlea. Hear Res 1995);89:14-20.
14. Gratton MA, Schmiedt RA, Schulte BA. Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis. Hear Res 1996;94(1-2):116-124.
15. Nakazawa K, Spicer SS, Gratton MA, Schulte BA. Localization of actin in basal cells of stria vascularis. Hear Res 1996;96:13-19.
16. Gratton MA, Schulte BA, Hazen-Martin DJ. Development and characterization of an inner ear type I fibrocyte culture. Hear Res 1996;99:71-78.
17. Gratton MA, Smyth BJ, Lam,CF, Boettcher FA, Schmiedt RA. Decline of the endocochlear potential correlates with decreasing Na,K-ATPase activity in the lateral wall of aged Mongolian gerbil. Hear Res 1997;108:9-16.
18. Gratton MA, Schulte BA, Smyth, NM. Quantification of strial area in quiet-reared young and aged gerbils. Hear Res 1997;114:1-9.
19. Spicer SS, Gratton MA, Schulte BA. Expression patterns of ion-transport enzymes in spiral ligament fibrocytes change in relation to strial atrophy in the aged gerbil cochlea. Hear Res 1997;111:93-102.
20. Thomopoulos GN, Spicer SS, Gratton MA, Schulte BA. Age-related thickening of basement membrane in stria vascularis membrane. Hear Res 1997;111:31-41.
21. Boettcher FA, Caldwell RK, Gratton MA, Miles LR, White DR. Effects of nimodipine on noise-induced hearing loss. Hear Res 1998;121:139-146.
22. Wangemann P, Cohn ES, Gruber DD, Gratton MA. Ca2+-dependence and nifedipine-sensitivity of vascular tone and contractility in the isolated superfused spiral modiolar artery in vitro. Hear Res 1998;18:90-100.
23. White DR, Boettcher FA, Miles LR, Gratton MA. Effectiveness of intermittent and continuous acoustic stimulation in preventing noise-induced hearing and hair cell loss. J Acoust Soc Am 1998;103:1566-1572.
24. Gratton MA, Meehan DT, Smyth BJ, Cosgrove DE. Strial marginal cells play a role in basement membrane homeostasis: in vitro and in vivo evidence. Hear Res 2002;163:27-36.
25. Gratton, MA and Vazquez. AE (2003) Age-Related Hearing Loss: Current Research. Curr Opin in Otolaryngol & HNS, 11: 367-371.
26. Gratton, M.A., Veldi, H.R., Meehan, D.T., Askew, C. and Cosgrove, D. (2005) Matrix metalloproteinase dysregulation in the stria vascularis of mice with Alport syndrome: implications for capillary basement membrane pathology. Am. J. Path., 166:1465-1474
27. Nie, L., Feng, W., Diaz, R., Gratton, M.A., Doyle, K.J. and Yamoah, E.N. (2005) Functional Consequences of Inhibition of Polyamine Synthesis by DFMO: Cellular Mechanisms for DFMO-mediated Ototoxicity. J. Biol. Chem. 280:1465-1474.
28. Nie, L., Gratton, M.A. Mu, K., Feng, W., and Yamoah, E.N. (2005) Expression and Functional Phenotype of Mouse ether-a-go-go-related gene K+ Channels in the Cochlea: Potential role in K+ Regulation in the Inner Ear. J. Neurosc. 25:8671-8679.
29. Rao, V., Meehan, D., Delimont, D., Nakajima, M., Wada. T., Gratton, M.A .and Cosgrove, D. (2006) Role for Macrophage Metalloelastase in Glomerular Basement Membrane Damage Associated with Alport Syndrome. Am. J. Path.169:32-46.
30. Bedrosian, J.C., Gratton, M.A., Brigande, J.V., Tang, W., Landau, J., Bennett, J. (2006) In vivo delivery of recombinant viruses to the fetal murine cochlea: Transduction characteristics and long term effects on auditory function. Mol. Ther. 14:328-335.
31. Gratton, M.A., Bateman, K.M., Cannuscio, J.F. and Saunders, J.C. (2008) Middle ear contribution to presbycusis in the Brown-Norway rat. Audiol. Neurotol. 13:37-52
32. Nie, L., Zhu, J., Gratton, M.A., Liao, A., Mu, K.J., Nonner, W., and Yamoah, E.N. (2008) Molecular Identity and Functional Properties of a Novel Cav3.1 Channel in Sensory Epithelia of Inner Ear, J. Neurophys. 100(4):2287-99
33. Bleier BS, Gratton MA, Leibowitz JM, Palmer JN, Newman JG, Cohen NA. (2008) Laser-welded endoscopic endoluminal repair of iatrogenic esophageal perforation: An animal model. Otolaryngol Head Neck Surg. 139(5):713-7
34. Bleier BS, Palmer JN, Gratton MA, And Cohen NA (2008) Laser Tissue Welding in the Rabbit Maxillary Sinus. Am Journal Rhin. 22(6):625-28.
35. Wang, X, Levic, S, Gratton, MA, Doyle, KJ, Yamoah, EN and Pegg,AE, (In Press) Spermine synthase deficiency leads to deafness and a profound sensitivity to -difluoromethylornithine. J. Biol. Chem.