Albee Messing, VMD, PhD

Position title: Professor Emeritus, Comparative Biosciences

VMD, PhD, University of Pennsylvania
Professor Emeritus, Comparative Biosciences

Contact Information

Waisman Center, Room 713B
1500 Highland Avenue
Madison, WI 53705
608-263-9191
amessing@wisc.edu
Alexander Disease Research
Requests 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.

Selected Publications

Pubmed

Ashton, N. J., Di Molfetta, G., Tan, K., Blennow, K., Zetterberg, H., & Messing, A. (2024). Plasma concentrations of glial fibrillary acidic protein, neurofilament light, and tau in Alexander disease. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 10.1007/s10072-024-07495-8. Advance online publication. https://doi.org/10.1007/s10072-024-07495-8
Stowe, N. A., Singh, A. P., Barnett, B. R., Yi, S. Y., Frautschi, P. C., Messing, A., Hagemann, T. L., & Yu, J. J. (2024). Quantitative diffusion imaging and genotype-by-sex interactions in a rat model of Alexander disease. Magnetic resonance in medicine, 91(3), 1087–1098. https://doi.org/10.1002/mrm.29917
Gammie, S. C., Messing, A., Hill, M. A., Kelm-Nelson, C. A., & Hagemann, T. L. (2024). Large-scale gene expression changes in APP/PSEN1 and GFAP mutation models exhibit high congruence with Alzheimer’s disease. PloS one, 19(1), e0291995. https://doi.org/10.1371/journal.pone.0291995
Anderson, N. E., Alexander, H. S., & Messing, A. (2023). Alexander disease: The story behind an eponym. Journal of the history of the neurosciences, 32(4), 399–422. https://doi.org/10.1080/0964704X.2023.2190354
Wang, L., Bukhari, H., Kong, L., Hagemann, T. L., Zhang, S. C., Messing, A., & Feany, M. B. (2022). Anastasis Drives Senescence and Non-Cell Autonomous Neurodegeneration in the Astrogliopathy Alexander Disease. The Journal of neuroscience : the official journal of the Society for Neuroscience, 42(12), 2584–2597. https://doi.org/10.1523/JNEUROSCI.1659-21.2021
Hagemann, T. L., Powers, B., Lin, N. H., Mohamed, A. F., Dague, K. L., Hannah, S. C., Bachmann, G., Mazur, C., Rigo, F., Olsen, A. L., Feany, M. B., Perng, M. D., Berman, R. F., & Messing, A. (2021). Antisense therapy in a rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment. Science translational medicine, 13(620), eabg4711. https://doi.org/10.1126/scitranslmed.abg4711
Boyd, M. M., Litscher, S. J., Seitz, L. L., Messing, A., Hagemann, T. L., & Collier, L. S. (2021). Pexidartinib treatment in Alexander disease model mice reduces macrophage numbers and increases glial fibrillary acidic protein levels, yet has minimal impact on other disease phenotypes. Journal of neuroinflammation, 18(1), 67. https://doi.org/10.1186/s12974-021-02118-x
Brenner, M., & Messing, A. (2021). Regulation of GFAP Expression. ASN neuro, 13, 1759091420981206. https://doi.org/10.1177/1759091420981206
Helman G, Takanohashi A, Hagemann TL, Perng MD, Walkiewicz M, Woidill S, Sase S, Cross Z, Du Y, Zhao L, Waldman A, Haake BC, Fatemi A, Brenner M, Sherbini O, Messing A, Vanderver A, Simons C. (2020). Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform. Human Mutation, 41(6), 1131. https://doi.org/10.1002/humu.24008
Messing, A., & Brenner, M. (2020). GFAP at 50. ASN neuro, 12, 1759091420949680. https://doi.org/10.1177/1759091420949680
Messing A. (2019). Refining the concept of GFAP toxicity in Alexander disease. Journal of Neurodevelopmental Disordorders. 2019 Dec 16;11(1):27. doi: 10.1186/s11689-019-9290-0.
Brenner M, Messing A, Olsen ML. (2019). AP-1 and the injury response of the GFAP gene. Journal of Neuroscience Research, 97(2):149-161. doi: 10.1002/jnr.24338.
Jones JR, Kong L, Hanna MG 4th, Hoffman B, Krencik R, Bradley R, Hagemann T, Choi J, Doers M, Dubovis M, Sherafat MA, Bhattacharyya A, Kendziorski C, Audhya A, Messing A, Zhang SC. (2018). Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes. Cell Reports, 25(4):947-958.e4. doi: 10.1016/j.celrep.2018.09.083.
Wang, L., Xia, J., Li, J., Hagemann, T. L., Jones, J. R., Fraenkel, E., Weitz, D. A., Zhang, S. C., Messing, A., & Feany, M. B. (2018). Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease. Nature communications, 9(1), 1899. https://doi.org/10.1038/s41467-018-04269-7
Hagemann TL, Powers B, Mazur C, Kim A, Wheeler S, Hung G, Swayze E, Messing A. (2018). Antisense suppression of glial fibrillary acidic protein as a treatment for Alexander disease. Annals of Neurology, 83(1):27-39. doi: 10.1002/ana.25118.
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, Messing A, Perng MD. (2017). Characterization of a panel of monoclonal antibodies recognizing specific epitopes on GFAP. PLoS One, 12(7):e0180694. doi: 10.1371/journal.pone.0180694.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Hagemann TL, Jobe EM, Messing A. (2012) Genetic ablation of Nrf2/antioxidant response pathway in Alexander disease mice reduces hippocampal gliosis but does not impact survival. PLoS One. 7(5):e37304.
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.
Cengiz P, Kleman N, Uluc K, Kendigelen P, Hagemann T, Akture E, Messing A, Ferrazzano P, Sun D. (2011) Inhibition of Na+/H+ exchanger isoform 1 is neuroprotective in neonatal hypoxic ischemic brain injury. Antioxidants & Redox Signaling. 14(10):1803-13.
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.
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.
Hagemann, T. L., Boelens, W. C., Wawrousek, E. F., & Messing, A. (2009). Suppression of GFAP toxicity by alphaB-crystallin in mouse models of Alexander disease. Human molecular genetics, 18(7), 1190–1199. https://doi.org/10.1093/hmg/ddp013