Headshot of Margaret Lomax

Research

Developmental neurobiology; molecular neurobiology; studies of developing neuronal cells and synapses; cytochrome oxidase; auditory system; gene arrays; deafness.

My research group uses modern molecular biological, molecular genetic and cell biological techniques to study both the development of the ear and the response of the inner ear to noise trauma. The inner ear is an important sensory organ that controls both balance and hearing. We are interested in three broad areas.

1. The role of ZIC transcription factors in the embryological development of the inner ear. This project is a collaboration with Dr. Kate Barald, also of the Dept. of Cell and Developmental Biology (CDB). We are studying the effects of chordin, a BMP4 antogonist, on the induction of ZIC genes in mouse otocyst-derived cell lines as they differentiate in culture to a neuronal phenotype. We also have identified genes that are expressed in the otocyst (the embryonic structure that develops into the ear) during early chick development.

2. The effects of noise damage on both the chick and rat inner ear. We use the chick as a model system for these studies because birds (and amphibians) can regenerate the important auditory (sensory) hair cells in the auditory epithelium after noise damage, whereas humans can not. Once we identify genes that are up-regulated following noise damage, we use all the tools of the cell biologist to examine the location of both the mRNA and protein in the normal chick basilar papilla and after noise damage. We are focusing on genes involved in two pathways: actin dynamics and ubiquitin-mediated protein turnover. Understanding the function of these genes is a major challenge. To investigate how the mammalian ear responds to noise overstimulation, we are using gene arrays to identify differentially regulated genes. These studies have led to investigations of several immediate early genes for both transcription factors and cytokines, and are part of a collaborative project with Dr. Richard Altschuler, CDB and KHRI. Damon Fairfield, a CDB graduate student, is investigating the stress response in the rat inner ear after noise damage. He developed molecular assays for stress response transcription factors (HSFs) and proteins (HSPs), which are known to protect other organs against various traumas.

3. The genetics of otosclerosis and other forms of hereditary deafness. There has been an explosion of research on the genetics of deafness during the last 10 years. At least 50 genes have been mapped in humans, and about 20 have been identified to date. Our colleague, Dr Marci Lesperance, a pediatric otolaryngologist studying families with inherited deafness, has identified mutations in the NOGGIN gene in two families with conductive hearing loss due to stapes fixation. and trying to map and identify which genes are involved. In collaboration with Dr. Lesperance, we are beginning to examine the role of noggin in bone and joint formation in the ear.

4. Muscle-specific expression of cytochrome c oxidase. We also have a long-standing interest in the molecular genetics of cytochrome c oxidase (COX)and, in collaboration with Dr. John Kennedy, Univ. of Illinois at Chicago, are examining the effects of electrical stimulation of intact muscle on expression of muscle-specific COX genes.

The Lomax Lab maintains a website of protocols, members, and materials. Below are individuals who are part of the Lomax lab, see lab website for additional lab members.



Publications

Representative Publications

  1. Altschuler RA, Fairfield D, Cho Y, Leonova E, Benjamin IJ, Miller JM, Lomax MI. Stress pathways in the rat cochlea and potential for protection from acquired deafness. Audiol Neurootol 7: 152-156, 2002.
  2. Cho Y, Gong TW, Stover T, Lomax MI, Altschuler RA. Gene expression profiles of the rat cochlea, cochlear nucleus, and inferior colliculus. J Assoc Res Otolaryngol 3: 54-67, 2002.
  3. Cho Y, Gong T-W, Kanicki AC, Altschuler RA, Lomax MI. Noise overstimulation induces immediate early genes in the rat cochlea. Molec. Brain Res. 120: 134-148, 2004.
  4. Fairfield D, Kanicki AC, Lomax MI, Altschuler R. Expression and localization of heat shock factor (Hsf1) 1 in the rodent cochlea. Hearing Research 173: 109-118, 2002.
  5. Fairfield D, Kanicki AC, Lomax MI, Altschuler R. Induction of heat shock protein 32 (Hsp32) in the rat cochlea following hyperthermia. Hearing Research 188: 1-11, 2004.
  6. Fairfield D, Lomax MI, Dootz GA, Shen S, Benjamin IJ, Dolan DF, Galecki A, Altschuler RA. Heat shock factor 1 (Hsf1) deficient mice exhibit decreased recovery of hearing following noise overstimulation. J. Neurosci. Res. in press, 2005.
  7. Gong T-WL, Besirli CG, Lomax MI. MACF1 gene structure: a hybrid of plectin and dystrophin. Mammalian Genome. 12: 852-861, 2001.
  8. Gong TW, Huang L, Warner SJ, Lomax MI. Characterization of the human UBE3B gene: structure, expression, evolution, and alternative splicing. Genomics 82: 143-152, 2003.
  9. Holt AG, Asako M, Lomax CA, MacDonald JW, Tong L, Lomax MI, Altschuler RA. Deafness-related plasticity in the inferior colliculus: gene expression profiling following removal of peripheral activity. J Neurochem 93: 1069-1086, 2005.
  10. Kanzaki S, Kawamoto K, Oh SH, Stover T, Suzuki M, Ishimoto S, Yagi M, Miller JM, Lomax MI, Raphael Y. From gene identification to gene therapy. Audiol Neurootol 7: 152-156, 2002.
  11. Le Prell CG, Dolan DF, Schacht J, Miller JM, Lomax MI, Altschuler RA. Pathways for protection from noise induced hearing loss. Noise Health 5: 1-17, 2003.
  12. Leonova EV, Fairfield DA, Lomax MI, Altschuler RA. Constitutive expression of Hsp27 in the rat cochlea. Hear Res 163: 61-70, 2002.
  13. Leonova EV, Lomax MI. Expression of the mouse Macf2 gene during inner ear development. Brain Res Mol Brain Res 105: 67-78, 2002.
  14. Lomax MI, Huang L, Cho Y, Gong T-WL, Altschuler RA. Differential display and gene arrays to examine auditory plasticity. Hear. Res. 147: 293-302, 2000.
  15. Lomax MI, Gong TW-L, Cho Y, Huang L, Oh S-H, Adler HJ, Raphael Y, Altschuler RA. Differential gene expression following noise trauma in birds and mammals. Noise & Health 3: 19-35, 2001.
  16. Oh S-H, Adler HJ, Raphael Y, Lomax MI. WDR1 co-localizes with ADF and actin in the normal and noise damaged chick cochlea. J. Comp. Neurol. 448: 399-409, 2002.
  17. Shin DH, Lee E, Chung YH, Mun GH, Park Jy J, Lomax MI, Oh SH. Subcellular localization of WD40 repeat 1 protein in PC12 rat pheochromocytoma cells. Neurosci Lett 367: 399-403, 2004.
  18. Stover T, Gong TL, Cho Y, Altschuler RA, Lomax MI. Expression of the GDNF family members and their receptors in the mature rat cochlea. Brain Res Mol Brain Res 76: 25-35, 2000.
  19. Stover T, Nam Y, Gong TL, Lomax MI, Altschuler RA. Glial cell line-derived neurotrophic factor (GDNF) and its receptor complex are expressed in the auditory nerve of the mature rat cochlea. Hear Res 155: 143-151., 2001.
  20. Warner SJ, Hutson MR, Oh SH, Gerlach-Bank LM, Lomax MI, Barald KF. Expression of ZIC genes in the development of the chick inner ear and nervous system. Dev. Dyn. 226: 702-712, 2003.
  21. Wong-Riley, M, A., Guo, N.J. Bachman, and M.I. Lomax. Human COX6A1 gene: promoter analysis, cDNA isolation and expression in the monkey brain. Gene,247:63-75, 2000.
  22. Lomax, M.I., L. Huang, Y. Cho, T.-W. L. Gong, and R. A. Altschuler. Differential display and gene arrays to examine auditory plasticity. Hearing Research, 147:293-302, 2000.
  23. Greene, C.C., P.M. McMillan, S. E. Barker, P. Kurnool, M.I. Lomax, M. Burmeister and M.M. Lesperance: DFNA25, a novel locus for dominant nonsyndromic hereditary hearing impairment, maps to 12q21-24. Am J Human Genetics, 68:254-260, 2001.
  24. Lomax, M.I., T.-W.L. Gong, Y. Cho, L. Huang, S.H. Oh, H.J. Adler, Y. Raphael, and R.A. Altschuler: Differential gene expression following noise trauma in birds and mammals. Noise & Health, 11:19-35, 2001.
  25. Stover, T., T.-W.L. Gong, Y. Cho, R.A. Altschuler, and M.I. Lomax: Glial cell line-derived neurotrophic factor (GDNF) and its receptor complex are expressed in mature rat cochlea. Hearing Research, 155:143-151, 2001.
  26. Gong, T.-W. L., Besirli, C.G., and Lomax, M.I. MACF1 gene structure: a hybrid of plectin and dystrophin. Mammalian Genome, 12:852-861, 2001.
  27. Cho, Y., T.-W.L. Gong, T. Stover, M. I. Lomax, and R. A. Altschuler. Gene expression profile of the rat cochlea, cochlear nucleus and inferior colliculus. JARO, 3:54-67, 2001.
  28. Leonova, E.V., Fairfield, D.A., Lomax, M.I. Altschuler, R.A. Constitutive expression of Hsp27 in the rat cochlea. Hearing Research, 163:61-70, 2002.
  29. Oh, S.-H., Adler, S.J., Raphael, Y., and Lomax, M.I.: WDR1 colocalizes with ADF and actin in the normal and noise damaged chick cochlea. J. Comp. Neurol., 448:399-409, 2002.
  30. Fairfield, D.A., A.C. Kanicki, M.I. Lomax, and R.A. Altschuler: Expression and localization of heat shock factor (Hsf1) 1 in the rodent cochlea. Hearing Research, 173:109-118, 2002.
  31. Altschuler, R.A., D.A. Fairfield, Y. Cho, E. Leonova, I.J. Benjamin, J.M. Miller, M.I. Lomax. Stress pathways in the rat cochlea and potential for protection from acquired deafness. Audiology Neurootology, 7:152-156, 2002.
  32. Kanzaki, S., Kawamoto, K., Oh, S.-H., Stover, T., Suzuki, M., Isimoto, S., Yagi, M., Miller, J. M., Lomax, M. I., Raphael, Y. From gene identification to gene therapy. Audiology Neurootology, 7:161-164, 2002.
  33. Warner, S.J., Hutson, M.R., Oh, S.-H., Gerlach-Bank, L.M., Lomax, M.I. and Barald, K.F.: Expression of ZIC genes in the development of the chick inner ear and nervous system. Developmental Dynamics, 226:702-712, 2003.
  34. Gong, T.-W. L., L. Huang, S.J. Warner, and M. I. Lomax (2003) Characterization of the human UBE3B gene: Structure, expression, evolution and alternative splicing. Genomics, In press.
  35. Warner, S.J., Hutson, M.R., Oh, S.-H., Gerlach-Bank, L.M., Lomax, M.I. and Barald, K.F.: Expression of ZIC genes in the development of the chick inner ear and nervous system. Developmental Dynamics, 226:702-712, 2003.
  36. Gong, T.-W. L., Huang, L., Warner, S.J., and Lomax, M.I.: Characterization of the human UBE3B gene: Structure, expression, evolution and alternative splicing. Genomics, 82:143-152, 2003.
  37. Fairfield, D.A., A.C. Kanicki, M.I. Lomax, and R.A. Altschuler: Induction of heat shock protein 32 (Hsp32) 1 in the rat cochlea following hyperthermia. Hearing Research, 188:1-11, 2004.
  38. Nair, TS, Kozma, KE, Hoefling, NL, Ueda, Y, Gong, T-W, Lomax, ML, Lansford, CD, Telian, S, Arts, HA, Satar, B, El-Kashlan, HK, Berryhill, W, Raphael, Y, Carey, TE. Identification and characterization of CTL2, an inner ear glycoprotein of 68 and 72kDa that is the target of antibody-induced hearing loss. Journal of Neuroscience, 24:1772-1779, 2004.
  39. Shin, D.H., E. Lee, Y.H. Chung, G.H. Mun, J.Y. Park, M.I. Lomax, and S.H. Oh: Subcellular localization of WD40 repeat protein 1 in PC12 rat pheochromocytoma cells. Neurosci. Lett. 399-403, 2004.
  40. Cho, Y., Gong, T.-W., Kanicki, A., Altschuler, R.A., and Lomax, M.I.: Noise overstimulation induces immediate early genes in the rat cochlea. Mol. Brain Res. 130: 134-148, 2004.
  41. Holt, A.G., Asako, M., Lomax, C.A., Tong, L., Lomax, M. I., Altschuler, R. A. Activity dependent plasticity in the inferior colliculus: Gene expression profiling following deafness. J. Neurochem., 93:1069-1093, 2005.
  42. Gong, T.W.L., Karolyi, J., McDonald, J., Kohrman, D., Camper, S., and Lomax, M.I.: Age-related changes in cochlear gene expression in normal and shaker-2 mice. JARO 7:317-328, 2006.

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