Michael Brenner Ph.D
Associate PrefessorUniversity of Alabama Intellectual and Developmental Disabilities Research Center
University of Alabama at Birmingham, Civitan International Research Center
Suite 516 CIRC Bld.
1719 6th Avenue South
Birmingham, AL 35294-0021
205-934-1011 (tel)
205-934-6571 (fax)
[email protected]
http://www.mrrc.uab.edu/
Biography/Curriculum Vitae:
Research Interests:
molecular biology of astrocytes
Narrative of Current Research Efforts:
Our laboratory studies the molecular biology of astrocytes, the most common cell type in the central nervous system (CNS). Astrocytes are responsible for many of the homeostatic controls in the CNS, and are also involved in complex developmental and functional interactions with neurons and oligodendrocytes. Our work focuses on the transcriptional regulation of a gene encoding an intermediate filament protein specific to astrocytes, glial fibrillary acidic protein (GFAP), and on the biological role of this protein. The GFAP gene is of interest because it is turned on as astrocytes mature, and its activity increases dramatically following almost any CNS injury. Thus, study of GFAP transcription will yield insights into mechanisms governing development, reaction to injury, and cell specificity. An important role for the GFAP protein is indicated by the fact that astrocytes have elaborated their own specific intermediate filament protein and by its greatly increased synthesis following injury.
In our transcriptional studies we have identified a GFAP promoter segment that permits transgenes to be expressed specifically in astrocytes, making it possible to test hypotheses about the function of almost any gene product in the CNS of a living animal. The GFAP promoter is also used for creation of disease models and for genetically modifying astrocytes for gene therapy. In studies of GFAP function, we have found that absence of the protein renders mice hypersensitive to traumatic spinal cord injury, revealing a novel role for GFAP in structural support. We have also discovered that mutations within the coding sequence of the GFAP gene are responsible for many cases of Alexander disease, a rare but often fatal neurodegenerative disorder of humans.
Major Honors and Awards:
1965 Graduated Harvard College Magna cum Laude
1966 United States Churchill Foundation Fellowship for year at Cambridge University, England
1966-1970 United States Public Health Service Training Grant
1970-71 American Cancer Society Postdoctoral Fellowship
1993 National Institutes of Health Award of Merit
1999 Grupo Carso Award: biennial award by the Fundación Mexicana para la Salud (Mexican Foundation for Health) for research on organ and tissue transplantation (joint with J. Segovia)
2000 Moore Award for best paper on clinico-pathologic correlation, annual meeting of the American Academy of Neuropathology (joint with coauthors A.B. Johnson, O. Boespflug-Tanguy, D. Rodriguez, J.E. Goldman and A. Messing).
2002 Outstanding poster award (selected for an oral presentation), Gordon Conference on Intermediate Filaments
2003 Outstanding poster award (selected for an oral presentation), American Society of Neurochemistry annual meeting
Representative Publications:
Messing, A., Goldman, J.E., Johnson, A.B. and Brenner, M. (2001). Alexander disease: new insights from genetics. J. Neuropathol. Exp. Neurogol. 60:263-273.
Sairanen, T.R., Lindsberg, P.J., Brenner, M., Carpen, O., and Siren, A. (2001). Differential cellular expression of tumor necrosis factor-alpha and Type I tumor necrosis factor receptor after transient global forebrain ischemia. J. Neurol.l Sci. 186:87-99.
Rodriguez, D., Gauthier, F., Bertini, E., N'guyen, G.U.S., Goizet, C., Gelot, A., Surtees, R. Pedespan, J-MK., Hernandorena, X., Troncosco., M., Brenner, M., Messing, A., Ponsot, G., Pham-Dinh, D., Dautigny, A. and Boespflug-Tanguy, O. (2001). Alexander Disease: spectrum of GFAP mutations and genotype-phenotype correlation. Am. J. Hum. Gen. 69:1134-1140.
Zhuo, H., Theis, W., Alvarez, Maya, I., Brenner, M., Willecke, R. and Messing, A. (2001). GFAP-Cre transgenic mice for manipulation of glial and neuronal function in vivo. Genesis 31:85-94.
Aoki, Y., Haginoya, K., Munakata, M., Yokoyama, H., Nishio, T., Togashi, N., Ito, T., Suzuki, Y., Kure, S., Iinuma, K., Brenner, M. and Matsubara, Y. (2001). A novel mutation in glial fibrillary acidic protein (GFAP) gene in a pataient with Alexander disease. Neurosci. Lett. 312:71-74.
Gorospe, J.R., Naidu, S., Johnson, A.B., Puri, V., Raymond, G.V., Jenkins, S.D., Pedersen, R.C., Lewis, D., Knowles, P. Fernandez, R., De Vivo, D., van de Knaap, M.S., Messing, A., Brenner, M. and Hoffman, E.P. (2002). Molecular findings in symptomatic and pre-symptomatic Alexander disease patients. Neurol. 58:1494-1500.
Li, R., Messing, A., Goldman, J.E. and Brenner, M. (2002). GFAP Mutations in Alexander Disease. Int. J. Dev. Neurosci. 20:259-268.
Nawashiro, H., Huang, S., Brenner, M., Shima, K. and Hallenbeck, J.M. (2002). ICP monitoring following bilateral carotid occlusion in GFAP-null mice. Acta Neurochir. Suppl. 81:269-270.
Messing, A. and Brenner, M. (2003). Alexander disease: GFAP mutations unify young and old. Lancet Neurol. 2:75.
Messing, A. and Brenner, M. (2003) GFAP: functional implications gleaned from studies of genetically-engineered mice. Glia 43:87-90.
Johnson, A.B. and Brenner, M. (2003). Alexander Disease: Clinical, Pathological and Genetic Features. J. Child Neurol. 18:625-632.
Lupien, C., Brenner, M., Guérin, S.L. and Salesse, C. Expression of glial fibrillary acidic protein in primary cultures of human Müller cells. Exp. Eye Res. 79:423-429.
Manuscripts in press
Thyagarajan, D., Chataway, T., Li, R., Gai, W.P., Brenner, M. (2004). Dominantly-inherited adult-onset leukocydstrophy with palatal tremor caused by a mutation in the glial fibrillary acidic protein gene. Mov. Disord. (in press).
Su, M., Hu, H., Lee, Y., d'Azzo, A., Messing, A. and Brenner, M. (2004). Expression specificity of GFAP transgenes. Neurochemi. Res. (in press).
Manuscripts submitted but not yet accepted
Hsiao, V.C., Rujin, T., Long, H., Perng, M.D., Brenner, M., Quinlan, R. and Goldman, J.E. Alexander disease mutation of GFAP causes filament network disorganization and increased filament stability. Undergoing revision for Journal of Cell Science following favorable reviews.
Liu, D., Brenner, M., Frerichs, K.U., Corpe, C., Simpson, I.A. and Hallenbeck, J.M. Regional Glut1 and Glut3 glucose transporter expression in ground squirrel brain during hibernation.
Manuscripts in preparation
Spatz, M, Yamamoto, T., Yamamoto, H., Brenner, M., Lenz, F.A. and McCarron, R.M. NO-mediated modification of endothelin receptor properties.
Ohtsuki, T., Brenner, M., Azzam, N., Azzam, R., Ruetzler. C. and Hallenbeck, J.M. Hibernation induces beta-globin-like mRNA in ground squirrel liver.
Ohtsuki, T., Brenner, M., Azzam, N., Azzam, R., Ruetzler. C. and Hallenbeck, J.M. Hibernation induces beta-globin-like mRNA in ground squirrel liver.
Messing, A., Li, R., Naidu, S. and Brenner, M.; Multiple offspring with the same GFAP mutation in a family with juvenile/adult Alexander disease.
Van der Knaap, M., Salomons, G.S., Li, R., Franzoni, E., Gutiérrez-Solana, L.G., Smit, L.M.E., Robinson, R., Ferrie, C., Cree, B., Reddy, A., Thomas N., Jakobs, C., Johnson, A., Messing, A. and Brenner, M.: Unusual variants of Alexander disease with DNA confirmation of the diagnosis.
Li, R., Salomons, G.S., Johnson, A., Van der Knaap, M., Naidu, S., Quinlan, R., Goldman, J.E., Jakobs, C., Cree, B., Messing, A. and Brenner, M. GFAP mutations in infantile, juvenile and adult forms of Alexander disease.
Lee, Y., Su, M., Messing, A. and Brenner, M.: Brain-region dependent expression of a GFAP regulatory sequence in transgenic mice.
Li, R., Salomons, G.S., Johnson, A., Van der Knaap, Boespflug-Tanguy, O., Rodriguez, D., Gorospe, J.R., Messing, A. and Brenner, M.: Propensity for paternal inheritance of de novo mutations in Alexander disease.
Created 10/27/2005 by
Last modified 3/31/2006 by Evette Mezger
