Back to Main

Faculty Detail    
Name MICHAEL BRENNER
  
Campus Address SHEL 977 Zip 2182
Phone  (205) 934-1011
E-mail  michaelb@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Neurobiology  Neurobiology Professor Emeritus
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Professor Emeritus

Graduate Biomedical Sciences Affiliations
Biochemistry and Structural Biology 
Cellular and Molecular Biology Program 
Medical Scientist Training Program 
Neuroscience 
Neuroscience Graduate Program 
Neurosciences 

Biographical Sketch 
Michael Brenner received his Ph.D. in Biochemistry from the University of California, Berkeley. He served on the faculty of Harvard College and Temple University Medical School, and was a Research Scientist at the National Institutes of Health before joining UAB in 1998. He is presently Professor Emeritus of Neurobiology with a secondary appointments in the Department of Physical Medicine Rehabilitation and Biochemistry and Molecular Genetics.

Society Memberships
Organization Name Position Held Org Link
American Society for Neurochemistry  member   
 



Research/Clinical Interest
Title
Molecular Sudies of Astrocytes in Health and Disease
Description
Our laboratory uses the tools of molecular and cellular biology to study astrocytes, the most common cell type in the central nervous system (CNS). Areas being investigated include transcriptional regulation and protein aggregate disease. Our work focuses on glial fibrillary acidic protein (GFAP), an intermediate filament protein. The GFAP gene is of interest because its activity is largely confined to astrocytes, is turned on as astrocytes mature, and increases dramatically following almost any CNS injury. Much of this investigation is being conducted by analyzing expression of reporter constructs in transgenic mice. An important practical goal is the identification of elements in the GFAP gene that can be used to direct expression of other genes to astrocytes in transgenic mice. One promoter we have developed has already been used by many laboratories for this purpose. We are continuing to try to improve its specificity and strength of expression. In studies of the functional role of GFAP, we have discovered that mice lacking the protein are hypersensitive to a whip-lash type injury that ruptures veins in the upper cervical spinal cord. This finding indicates that GFAP plays a previously unrecognized role in stabilizing the spinal cord blood vessels. The next step is to understand the basis for this support. We have also discovered that coding mutations in the GFAP gene are responsible for most cases of Alexander disease, a rare but usually fatal disorder. The pathological hallmark of Alexander disease is the presence in astrocytes of protein aggregates containing GFAP and the small stress proteins HSP27 and alphaB-crystallin. Although Alexander disease is quite rare, similar protein aggregate diseases are common, and include Parkinson's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), and various dementias, muscle and liver diseases. We are pursuing the mechanism by which GFAP mutations cause Alexander disease with the expectation that our findings will provide insights into these more common disorders as well.

Selected Publications 
Publication PUBMEDID
Brenner, M., Goldman, J.E., Quinlan, R.A. and Messing, A. (2009). Alexander disease: a genetic disorder of astrocytes. In Parpura, V. and Haydon, P., Astrocytes in (patho)physiology of the nervous system, Springer, pp. 591-648.   
Flint, D. and Brenner, M. (2011) Alexander disease, In Raymond, G.V., Eichler, F., Fatemi, A., and Naidu, S., Leukodystrophies), Mac Keith Press, London, pp. 106-129.   
Brenner, M., Johnson, A.B., Boespflug-Tanguy, O., Rodriguez, D., Goldman, J.E. and Messing, A. (2001). Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nature Genetics 27: 117-120.  11138011 
Su, M., Hu, H., Lee, Y., d'Azzo, A., Messing, A. and Brenner, M. (2004). Expression specificity of GFAP transgenes. Neurochem. Res. 29:2075-2093.  15662842  
Li, R., Johnson, A.B., Salomons, G.S., Goldman, J.E., Naidu, S., Quinlan, R., Cree, B., Ruyle, S.Z., Banwell, B., D’Hooghe, M., Siebert, J.R., Rolf, C.M., Cox, H., Reddy, A., Gutiérrez-Solana, L.G., Collins, A., Weller, R.O., Jakobs, C., Messing, A., Van der Knaap, M.S., and Brenner, M. (2005). GFAP mutations in infantile, juvenile and adult forms of Alexander disease. Annals Neurol. 57(3):310-326.  15732097 
Lee, Y., Su, M., Messing, A. and Brenner, M. (2006). Astrocyte heterogeneity revealed by expression of a GFAP-lacZ transgene. Glia 53:677–687.  16482522 
Der Perng, M.D., Su, M., Wen, S.F., Li, R., Gibbon, T., Prescott, A.R., Brenner, M. and Quinlan, R.A. (2006) The Alexander Disease-Causing Glial Fibrillary Acidic Protein Mutant, R416W, Accumulates into Rosenthal Fibers by a Pathway That Involves Filament Aggregation and the Association of alpha B-Crystallin and HSP27. Am. J. Hum. Genet. 79:197-213.  16826512 
Lee, Y., Su, M., Messing, A., Su, M. and Brenner, M. (2008) GFAP promoter elements required for region-specific and astrocyte-specific expression. Glia 56: 481-493.  18240313 
Cho, W., Brenner, M., Peters, N. and Messing, A. (2010). Drug Screening to Identify Suppressors of GFAP Expression. Hum Mol Gen. 19:3169-3178.  20538881 
Nawashiro, H., Messing, A., Azzam, N., and Brenner, M. (1998) Mice lacking GFAP are hypersensitive to traumatic cerebrospinal injury. NeuroReport 9: 1691-1696.

 		 9665584 
 

Keywords
astrocyte, GFAP, transcription, neurodegeneration, transgenic mice