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Norelle Wildburger, Ph.D.

Norelle Wildburger, Photo

Research

Gut Microbiota and Neurodegeneration:

Host-associated microbes (bacteria, archaea, fungi, and viruses) are largely non-pathogenic and densely populate the human gastrointestinal (GI) system or gut. These microbes comprise the human microbiota that modulate a wide array of biological processes from metabolism to brain function. Recent studies have revealed that altered gut microbiota homeostasis (i.e., dysbiosis) is related to autoimmune, neurodevelopmental/neuropsychiatric, and neurodegenerative diseases and disorders such as multiple sclerosis, autism spectrum disorder, and Parkinson’s disease (PD). PD was one of the first diseases linked to dysbiosis due to the common occurrence of GI symptoms. Multiple lines of evidence support the hypothesis that PD pathology involving a-Syn deposition and spread initiates in the enteric nervous system (i.e., gut nervous system). Yet, we lack a mechanistic understanding of how these complex gut-brain interactions evolve from the molecular to the mesoscale level of the neural circuity and ultimately into disease manifestation.

 

 

1. Modified from: Perez-Pardo, P. et al. The gut-brain axis in Parkinson’s disease: Possibilities for food-based therapies. European Journal of Pharmacology 817, 86–95 (2017).

Proteoforms:

Proteoforms are all protein products of a single gene, including post-translational modifications (PTMs), truncations, and sequence variants.2 The multitude of proteoform products of a single gene can result in changes in the physicochemical and biochemical properties of proteins, increasing the range of functional outcomes.3–6 Our goal is to characterize and quantify pathologically relevant proteins in their intact state (i.e., Top-down mass spectrometry) to characterize the full spectrum of proteoforms in brain7, cerebral spinal fluid, and blood.

 

2. Smith, L. M., Kelleher, N. L. & Consortium for Top Down Proteomics. Proteoform: a single term describing protein complexity. Nat. Methods 10, 186–187 (2013).

3. Lichti, C. F. et al. Post-translational Modifications in the Human Proteome. in Genomics and Proteomics for Clinical Discovery and Development. (ed. G, M.-V.) 101–136 (Springer Science and Business Media Dordrecht, 2014).

4. Smith, L. M. & Kelleher, N. L. Proteoforms as the next proteomics currency. Science 359, 1106–1107 (2018).

5. Aebersold, R. et al. How many human proteoforms are there? Nat. Chem. Biol. 14, 206–214 (2018).

6. Schaffer, L. V. et al. Identification and Quantification of Proteoforms by Mass Spectrometry. Proteomics 19, e1800361 (2019).

7. Wildburger, N. C. et al. Diversity of Amyloid-beta Proteoforms in the Alzheimer’s Disease Brain. Sci Rep 7, 9520 (2017).

Curriculum Vitae

Education  
2008 Summer Undergraduate Research Fellow, Washington University, St. Louis • BioMedRAP (Research Apprenticeship Program)
2009 Summer Undergraduate Research Fellow, Washington University, St. Louis • Harvey A. Friedman Center for Aging/NSF-REU
2010 B.Sc. Neuroscience, Baylor University, Waco
2015 Ph.D. Neuroscience, UTMB (in conjunction with MD Anderson Cancer Center), Galveston/Houston
2015-2019 Postdoc Neurodegeneration (Alzheimer), Washington University, St. Louis
Since 2019 Postdoc Neurodegeneration (Parkinson), University of Veterinary Medicine

Group:

Wildburger, Norelle C., Dr.

Postdoc

Tel: +49 511 953 8728

Fax: +49-511 953-8581

E-Mail: Norelle.Wildburger@tiho-hannover.de

Hartke, Anna-Sophia, B.Sc.

Master student

Tel: +49 511 953 8722

Fax: +49-511 953-8581

E-Mail: Anna-Sophia.Hartke@tiho-hannover.de

Original Publications

1.     Neuroprotective effects of blockers for T-type calcium channels. ‡*Wildburger, N.C., Lin-Ye, A., Baird, M.A., Lei, D., and Bao. J. (2009). Molecular Neurodegeneration; doi:10.1186/1750-1326-4-44.

·       Marked as “Highly Accessed”

2.     The Fibroblast Growth Factor14:Voltage-gated Sodium Channel Complex is a New Target of Glycogen Synthase Kinase 3 (GSK3). †*Shavkunov, A.S, *Wildburger, N.C., Buzhgyan, T., Panova, N. Veselenak, R., Bourne, N., and Laezza, F. (2013). Journal of Biological Chemistry, 288, 19370-19385.

 

3.     The Nav1.2 channel is regulated by GSK3. James, T.F., Nenov, M.N., Wildburger, N.C., Lichti, C.F., Luisi, J., Vergara, F., Panova-Elektronova, N.I., Nilsson, C.L., Rudra, J., Green, T.A., Labate, D., and Laezza, F. (2015). Biochim Biophys Acta, 1850, 832-844.

 

4.     Quantitative Proteomics Reveals Protein-Protein Interactions with Fibroblast Growth Factor12 as a Component of the Nav1.2 Macromolecular Complex in Mammalian Brain. #Wildburger, N.C., Ali, S.R., Hsu, W-C.J., Shavkunov, A.S., Nenov, M.N., Lichti, C.F., LeDuc, R.D., Mostovenko, E., Panova-Elektronova, N., Emmett, M.R., Nilsson, C.L., and Fernanda Laezza. (2015). Molecular and Cellular Proteomics, 14, 1288-300.

 

5.     ESI-MS/MS and MALDI-IMS Localization Reveal Alterations in Phosphatidic Acid, Diacylglycerol, and DHA in Glioma Stem Cell Xenografts. #Wildburger, N.C., Wood, P.L., Gumin, J., LeDuc, D.R., Lichti, C.F., Emmett, M.R., Lang, F.F., and Nilsson, C.L. (2015). Journal of Proteome Research, 14, 2511-2519.

 

6.     The Proteomic Landscape of Glioma Stem-Like Cells. Lichti, C.F., Wildburger, N.C., Shavkunov, A.S., Mostovenko, E., Liu, H., Sulman, E.P., Nilsson, C.L. (2015). EuPA Open Proteomics, 8, 85-93.

 

7.     Integrated Transcriptomic and Glycomic Profiling of Glioma Stem Cell Xenografts. #*Wildburger, N.C., *Zhou, S., Zacharias, L.G., Kroes, R.A., Moskal, J.R., Schmidt, M., Mivzaei, P., Gumin, J., Lang, F.F., Mechref, Y. and Nilsson, C.L. (2015). Journal of Proteome Research, 14, 3932-3939.  

 

8.     Quantitative Proteomics and Transcriptomics Reveals Metabolic Differences in Attracting and Non-Attracting Human-in-Mouse Glioma Stem Cell Xenografts and Stromal Cells.#Wildburger, N.C., Lichti, C.F., LeDuc, R.D., Schmidt, M., Kroes, R.A., Moskal, J.R., and Nilsson, C.L. (2015). EuPA Open Proteomics, 8, 94-103.

 

9.     Soluble Amyloid-beta Aggregates from Human Alzheimer’s Disease Brains. ‡Esparza, T.J., Wildburger, N.C., Jiang, H., Gangolli, M., Cairns, N.J., Bateman, R.J., and David L. Brody, D.L. (2016). Scientific Reports, 6, 38187.

 

10. ). CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability. Hsu, W-C.J., Scala, F., Nenov, M.N., Wildburger, N.C., Elferink, H., Chesson, C.B., Buzhdygan, T., Sohail, M., Shavkunov, A.S., Panova, N.I., Nilsson, C.L., Rudra, J.S., Lichti, C.F., and Laezza, F. (2016FASEB, 30, 2171-2186.

 

11. PPARgamma agonists rescue increased phosphorylation of FGF14 at S226 in the Tg2576 mouse model of Alzheimer's disease. Hsu, W-C.J., Wildburger, N.C., Haidacher, S.J., Nenov, M.N., Folorunso, O., Singh, A.K., Chesson, B.C., Franklin, W.F., Cortez, I., Sadygov, R.G., Dineley, K.T., Rudra, J.S., Taglialatela, G., Lichti, C.F., Denner, L., Laezza, F. (2017). Experimental Neurology, 295, 1-17.

 

12. The driving regulators of the connectivity protein network of brain malignancies. Tahmassebi, A., Pinker-Domenig, K., Wengert, G., Lobbes, M., Stadlbauer, A., Wildburger, N.C., Romero, F.J., Morales, D.P., Castillo, E., Garcia, A., Botella, G., Meyer-Bäse, A. (2017). Proc. SPIE 10216, Smart Biomedical and Physiological Sensor Technology XIV, 1021605.

 

13. Diversity of Amyloid-beta Proteoforms in the Alzheimer’s Disease Brain. #Wildburger, N.C. Esparza, T.J., LeDuc, R.D., Fellers, R.T., Thomas, P.M., Cairns, N.J., Kelleher, N.L, Bateman, R.J., and Brody, D.L. (2017). Scientific Reports, 7, 9520.

 

14. Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway. Scala, F., Nenov, M., Crofton, E., Singh, A.K., Folorunso, T., Zhang, Y., Chesson, B.C., Wildburger, N.C., James, T.F., Alshammari, M., Alshammari, T., Elferink, H., Grassi, C., Kasper, J.M., Smith, A.E., Hommel, J.D., Lichti, C.F., Rudra, J., D’Ascenzo, M., Green, T., and Laezza, F. A (2018). Cell Reports, 23, 555-567.

 

15. Amyloid-β plaques in clinical Alzheimer’s disease brain incorporate stable isotope tracer In vivo and exhibit nanoscale heterogeneity. #Wildburger, N.C., Gyngard, F., Guillermier, C., Patterson, BW., Elbert, D., Mawuenyega, K.G., Schneider, T., Green, K., Roth, R., Schmidt, R.E., Cairns, N.J., Benzinger, T.L.S., Steinhauser, M.L., Bateman, R.J. (2018). Frontiers in Neurology. 9: 169.

 

16. The structure of amyloid-β dimers in Alzheimer's disease brain: a step forward for oligomers. Bateman R.J., Mawuenyega K.G., Wildburger N.C. (2019). Brain, 142, 1168-1169.

 

17.  Inter-laboratory Study for Characterizing Monoclonal Antibodies by Top-Down and Middle-Down Mass Spectrometry. Srzentić, K., …. Wildburger, N.C., Yates III, J.R., Yoon, S.H., Young, N. L., & Zhou, M., (2020). JASMS. Accepted.

Reviews

1.     Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase. Wildburger, N.C. & Laezza, F.L. (2012). Frontiers in Molecular Neuroscience. 5:80.

 

2.     Non-canonical Soluble Amyloid-beta Aggregates and Plaque Buffering: Controversies and Future Directions for Target Discovery in Alzheimer’s Disease. Brody, D.L., Jiang, H., Wildburger, N.C., and Thomas J. Esparza, T.J. (2017). Alzheimer's Research & Therapy, 9, 62.

 

3.     SILK studies — capturing the turnover of proteins linked to neurodegenerative disease. Paterson R.W., Gabelle A., Lucey B.P., Barthelemy N., Leckey C.A., Hirtz C., Lehmann, S., Sato C., Patterson B.W., West T., Yarasheski K., Rohrer, J.D., Wildburger N.C., Schott J.M., Karch C.M., Wray S., Miller T., Elbert D.L., Zetterberg H., Fox, N.C., and Bateman R.J. (2019). Nature Reviews Neurology, 15, 419–427.

 

4.     The Lysosome as both Target and Facilitator of Parkinson’s disease Neurodegeneration: Bidirectional Loop between the Lysosome and Alpha-Synuclein Proteoforms. #Wildburger, N.C., Hartke, A-S., Schidlitzki, A., #Richter-Assêncio, F. (2020). Submitted.

 

* authors contributed equally

# corresponding author

† listed in the top three most read JBC neurobiology papers (http://neuro.jbc.org/browse/most-read)

‡ Press release

Patents

1.     US-2018-0372720-A1, “Stable Isotope Labeling Kinetics – Secondary Ion Mass Spectrometry (SILK SIMS) and methods of use thereof (Publication 27 Dec 2018).

Book Chapters

  1. Post-Translational Modifications within the Human Proteome. In: Markó-Varga, G. (eds) Genomics and Proteomics for Clinical Discovery and Development. Springer, Lund, Vol. 6, pp 101-136, 201
  2. Neuromethods: Lipidomics; Paul L. Wood (ed.); Series Editor: Wolfgang Walz; MALDI-Imaging Mass Spectrometry of Brain Lipids, Norelle C. Wildburger. Springer, New York, Vol. 125, pp 45-59, 2017.  

Ph.D.
Norelle Wildburger, PhD
Tel.:+49 511 953-8728
Fax.:+49 511 953-8581

Address

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