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KATHLEEN MAGUIRE-ZEISS

Ph.D. 1987 (Pharmacology), Pennsylvania State University
College of Medicine
Phone: 202.687.2791
Fax: 202.687.0617
E-mail: km445@georgetown.edu


Dr. Maguire-Zeiss' laboratory is focused on understanding the molecular mechanisms involved in age-related neurodegenerative diseases. In particular, we are investigating the vulnerability of the nigrostriatal pathway in Parkinson’s disease (PD). Although the etiology of PD is currently unknown it is thought to involve both genetic vulnerability and environmental toxicants. We are currently following several lines of investigation with regard to PD pathogenesis. At the most basic science level we are studying the role of dopamine and alpha-synuclein in PD. Overexpression of and mutations in alpha-synuclein have been linked to familial PD. In addition, changes in the structure of this protein have been identified in toxicant models of PD. Utilizing both in vitro and in vivo models we are studying the effect of dopamine and dopamine quinone formation on alpha-synuclein protein conformation. We are also developing therapeutic interventions that will both alter alpha-synuclein toxic conformer formation and prevent cell death. Interference with alpha-synuclein aggregate formation or dissolution of existing aggregates is hypothesized to attenuate the pathophysiology of PD. To address this hypothesis we are employing an approach that utilizes humanized single chain antibodies (scFvs) that recognize structural epitopes on alpha-synuclein. In addition, to address the combination of genetic vulnerability and neurotoxicant exposure on PD pathogenesis we are utilizing transgenic mice that overexpress alpha-synuclein and chronic exposure to neurotoxicants. Using this paradigm we are studying the role of microglia, glutathione peroxidase and oxidative stress in cellular dysfunction.


Maguire-Zeiss Laboratory

Publications:

  1. Su X*, Maguire-Zeiss KA*, Giuliano R, Prifti L, Venkatesh K and Federoff HJ. Synuclein activates microglial in a model of Parkinson’s disease. Neurobiology of Aging, in press; *both authors contributed equally, 2007.
  2. Mhyre, TR, R Loy, PN Tariot, LA Profenno, KA Maguire-Zeiss, D Zhang, PD Coleman and HJ Federoff. Proteomic analysis of peripheral leukocytes in Alzheimer’s disease patients treated with divalproex sodium. Neurobiology of Aging, in press, 2007.
  3. Sortwell, C, WJ Bowers, SE Counts, MR Pitzer, MF Fleming, SO McGuire, KA Maguire-Zeiss, HJ Federoff and TJ Collier. Effects of ex vivo transduction of mesencephalic reaggregates with bcl-2 on grafted dopamine neuron survival. Brain Res. 1134:33-44, 2007.
  4. Maguire-Zeiss, KA, CI Wang, E Yehling, MA Sullivan, DW Short, X Su, G Gouzer, LA Henricksen, CA Wuertzer and HJ Federoff. Identification of human a-synuclein specific single chain antibodies. Biochemical and Biophysical Research Communications, 349:1198-1205, 2006.
  5. Bowers, W.J., M.A. Mastrangelo, H.A. Southerland, D.F. Howard, K.A. Maguire-Zeiss, and H.J. Federoff.  Neuronal precursor-restricted transduction via in utero CNS gene delivery of a novel bipartite HSV amplicon/transposase hybrid vector.  Molecular Therapy, 13 (3):580-588, 2005.
  6. Richfield EK, Maguire-Zeiss KA, Vonkeman HE, Voorn P. Preferential loss of Preproenkephalin versus preprotachykinin neurons from the striatum of Huntington's disease patients.  Annals of Neurology, 38:852-861, 1995.
  7. Maguire-Zeiss KA, Li ZW, Shimoda LMN, Hamill RW. Calbindin D28k mRNA in hippocampus, superior temporal gyrus and cerebellum: comparison between control and Alzheimer Disease subjects.  Molec Brain Res., 30:362-366, 1995.
  8. Richfield EK, Maguire-Zeiss KA, Cox C, Gilmore J, Voorn P. Reduced expression of preproenkephalin in striatal neurons from Huntington's Disease patients.  Annals of Neurology, 37:335-343, 1995.
  9. Horikoshi N*, Maguire KA*, Kralli A, Maldonado E, Reinberg D, Weinmann R.  Direct interaction between adenovirus E1A and the TATA-box binding protein TFIID.  Proc Natl Acad Sci USA, 88: 5124-5128, (*both authors contributed equally), 1991.
  10. Maguire KA, Shi X-P, Rosenberg M, Rappaport J, Horikoshi N, Weinmann R.  Interactions between adenovirus E1A and members of the AP-1 family of cellular transcription factors.  Oncogene, 6: 1417-1422, 1991.
  11. Webb ML, Maguire KA, Jacob ST.  Novobiocin inhibits initiation of RNA polymerase II-directed transcription of the mouse metallothionein-I gene independent of its effect on DNA topoisomerase II.  Nucleic Acids Res, 15:  8547-8560, 1987.
  12. Maguire KA, Webb ML, Garg LC, Jacob ST.  Accurate initiation of mouse metallothionein-I gene transcription using a fractionated nuclear extract from a hepatoma.  J Biol Chem, 262: 3231-3235, 1987.
  13. Maguire KA, Jacob ST.  Cell-free synthesis of tumor-type poly(A) polymerase.  Biochemistry, 25: 1515-1529, 1986.
  14. Rose KM, Maguire KA, Wurpel JND, Stetler DA, Marquez ED.  Monoclonal antibodies directed against mammalian RNA polymerase I.  J Biol Chem, 258: 12976-12981, 1983.

Reviews and Editorials:

  1. Maguire-Zeiss KA, Short DW, Federoff HJ. Synuclein, dopamine and oxidative stress: co-conspirators in Parkinson’s disease?  Molecular Brain Research, 134:1:18-23, 2005.
  2. Maguire-Zeiss KA and Federoff HJ. Safety of Viral Vectors for Neurological Gene Therapies.  Current Opinion in Molecular Therapy, 6(5): 473-81, 2004.
  3. Luo, Y, Henricksen, LA, Maguire-Zeiss KA, and Federoff HJ. Development of Nurr1 Stable Cell Lines for the Identification of Downstream Targets. In:  Parkinson's Disease; The Life Cycle of the Dopamine Neuron, 991: 354-358; Ann. N.Y. Acad. Sci., Eds. H.J. Federoff, R. E. Burke, S. Fahn and G. Fiskum, 2003.
  4. Maguire-Zeiss KA and Federoff HJ. Convergent Pathobiologic Model of Parkinson's Disease. In:  Parkinson's Disease; The Life Cycle of the Dopamine Neuron, 991: 152-166; Ann. N.Y. Acad. Sci., Eds. H.J. Federoff, R. E. Burke, S. Fahn and G. Fiskum, 2003.
  5. Maguire-Zeiss KA, Bowers WJ, Federoff HJ. Somatic Mosaic Approaches and the Aging Brain. Neurobiology of Aging, 23: 977-984, 2002. 
  6. Maguire-Zeiss KA, Bowers WJ, Federoff HJ. HSV vector-mediated gene delivery to the central nervous system. Current Opinion in Molecular Therapeutics, 3:482-490, 2001.
  7. Bowers WJ, Maguire-Zeiss KA, Harvey BK, Federoff HJ. Gene Therapeutic Approaches to the Treatment of Parkinson’s Disease. Clinical Neuroscience Research, 1(6):483-495, 2001.
  8. Jacob ST, Terns MP, Maguire KA.  Polyadenylate Polymerases from Normal and Cancer Cells and Their Potential Role in Messenger RNA Processing: A Review.  Cancer Res, 49: 2827-2833, 1989.

Books or Chapters in books, and publications in other journals:

  1. Maguire-Zeiss KA and Federoff HJ. Novel Gene Therapeutic Strategies for Neurodegenerative Diseases. In: Opportunities and Challenges of the Therapies Targeting CNS Regeneration, Ernst Schering Research Foundation, Perez, Mitrovic, Baron Van Evercooren, Eds., Springer Berlin, Heidelberg, New York, pp. 147-171, 2005.
  2. Maguire-Zeiss KA, Bowers WJ, Federoff HJ. HSV Amplicon Vectors in Neuronal Apoptosis Studies.  In Neuromethods, 37: 61-82; Apoptosis Methods and Protocols, Editor, Andrea LeBlanc, 2nd Edition, Humana Press, Totowa, NJ, 2002.