Albee Messing

Albee Messing VMD, PhD

VMD, PhD, University of Pennsylvania
Waisman Center Director
Faculty Core Director, Rodent Models Core
Professor, Comparative Biosciences

Contact Information:

Waisman Center
1500 Highland Avenue
Madison, WI 53705
Lab Website: Alexander Disease
Request for Materials

Research Statement

Research in my laboratory is directed at understanding developmental and pathologic aspects of glial cell biology in the nervous system of the mouse, with a particular focus on astrocytes and their major intermediate filament protein, GFAP. Our main strategies involve genetic manipulation of glial gene expression using transgenic techniques, and gene targeting in embryonic stem cells, to generate mutant strains of mice. Current projects address a variety of topics such as regulation of gene expression, the role of GFAP mutations and accumulation in the pathogenesis of Alexander disease. A major effort is devoted to devising novel therapeutic strategies for treatment of this disorder, and identifying biomarkers to permit monitoring severity or progression of the disease.

Representative Publications

Moody LR, Barrett-Wilt GA, Sussman MR, Messing A. (2017) Glial fibrillary acidic protein exhibits altered turnover kinetics in a mouse model of Alexander disease. Journal of Biological Chemistry. 7;292(14):5814-5824. doi: 10.1074/jbc.M116.772020.

Lin NH, Huang YS, Opal P, Goldman RD, Messing A, Perng MD. (2016) The role of gigaxonin in the degradation of the glial-specific intermediate filament protein GFAP. Molecular Biology of the Cell. 15;27(25):3980-3990.

Pekny M, Pekna M, Messing A, Steinhäuser C, Lee JM, Parpura V, Hol EM, Sofroniew MV, Verkhratsky A. (2016) Astrocytes: a central element in neurological diseases. Acta Neuropathologica. 131(3):323-45. doi: 10.1007/s00401-015-1513-1.

Wang L, Hagemann TL, Messing A, Feany MB. (2016) An In Vivo Pharmacological Screen Identifies Cholinergic Signaling as a Therapeutic Target in Glial-Based Nervous System Disease. Journal of Neuroscience. 3;36(5):1445-55. doi: 10.1523/JNEUROSCI.0256-15.2016.

Wang L, Hagemann TL, Kalwa H, Michel T, Messing A, Feany MB. (2015) Nitric oxide mediates glial-induced neurodegeneration in Alexander disease. Nature Communications. 26;6:8966. doi: 10.1038/ncomms9966.

Brenner M, Messing A. (2015) A new mutation in GFAP widens the spectrum of Alexander disease. European Journal of Human Genetics. 23(1):1-2. doi: 10.1038/ejhg.2014.99.

Helman G, Van Haren K, Bonkowsky JL, Bernard G, Pizzino A, Braverman N, Suhr D, Patterson MC, Ali Fatemi S, Leonard J, van der Knaap MS, Back SA, Damiani S, Goldman SA, Takanohashi A, Petryniak M, Rowitch D, Messing A, Wrabetz L, Schiffmann R, Eichler F. (2015) Disease specific therapies in leukodystrophies and leukoencephalopathies. Molecular Genetics and Metabolism. 114(4):527-36. doi: 10.1016/j.ymgme.2015.01.014.

Walker AK, Daniels CM, Goldman JE, Trojanowski JQ, Lee VM, Messing A. (2014) Astrocytic TDP-43 pathology in Alexander disease. Journal of Neuroscience. 7;34(19):6448-58. doi: 10.1523/JNEUROSCI.0248-14.2014.

Cotrina ML, Chen M, Han X, Iliff J, Ren Z, Sun W, Hagemann T, Goldman J, Messing A, Nedergaard M. (2014) Effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of Alexander disease. Brain Research. 25;1582:211-9. doi: 10.1016/j.brainres.2014.07.029.

Chen MH, Hagemann TL, Quinlan RA, Messing A, Perng MD. (2013) Caspase cleavage of GFAP produces an assembly-compromised proteolytic fragment that promotes filament aggregation. ASN Neuro. 19;5(5):e00125. doi: 10.1042/AN20130032.

Cunningham R, Jany P, Messing A, Li L. (2013) Protein changes in immunodepleted cerebrospinal fluid from a transgenic mouse model of Alexander disease detected using mass spectrometry. Journal of Proteome Research. Feb 1;12(2):719-28.

Hagemann TL, Paylor R, Messing A. (2013) Deficits in adult neurogenesis, contextual fear conditioning, and spatial learning in a Gfap mutant mouse model of Alexander disease. Journal of Neuroscience. 20;33(47):18698-706. doi: 10.1523/JNEUROSCI.3693-13.2013.

Jany PL, Hagemann TL, Messing A. (2013) GFAP expression as an indicator of disease severity in mouse models of Alexander disease. ASN Neuro. 5(1):e00109.

Yeo S, Bandyopadhyay S, Messing A, Brenner M. (2013) Transgenic analysis of GFAP promoter elements. Glia. 61(9):1488-99. doi: 10.1002/glia.22536.

Flint D, Li R, Webster LS, Naidu S, Kolodny E, Percy A, van der Knaap M, Powers JM, Mantovani JF, Ekstein J, Goldman JE, Messing A, Brenner M. (2012) Splice site, frameshift, and chimeric GFAP mutations in Alexander disease. Human Mutation. Jul;33(7):1141-8.

Messing A, Li R, Naidu S, Taylor JP, Silverman L, Flint D, van der Knaap MS, Brenner M. (2012) Archetypal and new families with Alexander disease and novel mutations in GFAP. Archives of Neurology. Feb;69(2):208-14.

Messing A, Brenner M, Feany MB, Nedergaard M, Goldman JE. (2012) Alexander disease. Journal of Neuroscience. Apr 11;32(15):5017-23.

Lapash Daniels CM, Austin EV, Rockney DE, Jacka EM, Hagemann TL, Johnson DA, Johnson JA, Messing A. (2012) Beneficial effects of nrf2 overexpression in a mouse model of alexander disease. Journal of Neuroscience. Aug 1;32(31):10507-15.

Toops KA, Hagemann TL, Messing A, Nickells RW. (2012) The effect of glial fibrillary acidic protein expression on neurite outgrowth from retinal explants in a permissive environment. BMC Research Notes. Dec 22;5:693.

Prust M, Wang J, Morizono H, Messing A, Brenner M, Gordon E, Hartka T, Sokohl A, Schiffmann R, Gordish-Dressman H, Albin R, Amartino H, Brockman K, Dinopoulos A, Dotti MT, Fain D, Fernandez R, Ferreira J, Fleming J, Gill D, Griebel M, Heilstedt H, Kaplan . (2011) GFAP mutations, age at onset, and clinical subtypes in Alexander disease. Neurology. Sep 27;77(13):1287-94.

Cho W, Brenner M, Peters N, Messing A. (2010) Drug screening to identify suppressors of GFAP expression. Human Molecular Genetics. Aug 15;19(16):3169-78.

Meisingset TW, Risa Ø, Brenner M, Messing A, Sonnewald U. (2010) Alteration of glial-neuronal metabolic interactions in a mouse model of Alexander disease. Glia. Aug;58(10):1228-34.

Messing A, LaPash Daniels CM, Hagemann TL. (2010) Strategies for treatment in Alexander disease. Neurotherapeutics. 7(4):507-15. doi: 10.1016/j.nurt.2010.05.013.

Hagemann TL, Boelens WC, Wawrousek EF, Messing A. (2009) Suppression of GFAP toxicity by alphaB-crystallin in mouse models of Alexander disease. Human Molecular Genetics. 1;18(7):1190-9. doi: 10.1093/hmg/ddp013.

Cho W, Hagemann TL, Johnson DA, Johnson JA, Messing A. (2009) Dual transgenic reporter mice as a tool for monitoring expression of glial fibrillary acidic protein. Journal of Neurochemistry. Jul;110(1):343-51.