Protein conformation in cell signaling and neurodegeneration.
Current Projects
I. Conformationally dynamic proteins in neurodegenerative cell signaling.
Neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and prion diseases are characterized by highly stable misfolded protein aggregates known as amyloids. These aggregates often arise from misfolding of endogenous proteins, however it is unclear how these protein aggregates propogate signals to induce neurodegeneration. One focus of the Mayfield lab is to understand how protein aggregates participate in cell signaling in neurodegenerative disease.
Related publications
Mayfield, J. E., Wang, J., Tovell, H., Taylor, S. S., Gonias, S. L. and Sigurdson, C. J. “Cellular Prion Protein Engages the N-Methyl-d-Aspartate Receptor through N- and C-Terminal Domains.” Biochemistry (2026). https://doi.org/10.1021/acs.biochem.6c00011. PMID: 41860118 (Pubmed)
Mayfield, J. E.&, Rajic, A. J.&, Aguilar-Calvo, P., Soldau, K., Flores, S., Lawrence, R., Choudhury, B., Ghassemian, M., Pizzo, D. P., Wagner, S. L., Danque, G. A., Sumowski, P., Hansen, L. A., Goodwill, V., Esko, J. D. & Sigurdson, C. J. Multi-omic analysis of meningeal cerebral amyloid angiopathy reveals enrichment of unsubstituted glucosamine and extracellular proteins. J Neuropathol Exp Neurol (2025). https://doi.org/10.1093/jnen/nlaf018. PMID: 40156913 (Pubmed)
Lin, J.&, Callender, J. A.&, Mayfield, J. E.&, McClatchy, D. B., Ojeda-Juarez, D., Pourhamzeh, M., Soldau, K., Kurt, T. D., Danque, G. A., Khuu, H. K., Ronson, J. E., Pizzo, D. P., Du, Y., Gruber, M. A., Sevillano, A. M., Wang, J., Orru, C. D., Chen, J., Funk, G., Aguilar-Calvo, P., Aulston, B. D., Roy, S., Rho, J. M., Bui, J. D., Newton, A. C., Lipton, S. A., Caughey, B., Patrick, G. N., Dore, K., Yates Iii, J. R. & Sigurdson, C. J. Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice. J Clin Invest (2025). https://doi.org/10.1172/JCI186432. PMID: 40185484 (Pubmed)
II. Endo/sarcoplasmic reticulum Ca2+ storage, handling, and signaling.
Calcium ions (Ca2+) are a major secondary messenger in eukaryotic cells and dictate processes such as muscle contraction and neuronal signaling. Cytosolic Ca2+ levels are held in the nano- to micromolar range but are elevated through release of Ca2+ from intracellular high-capacity stores located within the lumen of the endo/sarcoplasmic reticulum (ER/SR). The Mayfield lab is interested in how these stores are generated, maintained, and accessed during cell signaling to drive biological phenomena.
Related publications
Mayfield, J. E. & Dixon, J. E. Emerging mechanisms of regulation for endoplasmic/sarcoplasmic reticulum Ca2+ stores by secretory pathway kinase FAM20C. Curr Opin Chem Biol 74, 102279 (2023). https://doi.org/10.1016/j.cbpa.2023.102279. PMID: 36966700 (Pubmed)
Pollak, A. J., Liu, C., Gudlur, A., Mayfield, J. E., Dalton, N. D., Gu, Y., Chen, J., Heller Brown, J., Hogan, P. G., Wiley, S. E., Peterson, K. L. & Dixon, J. E. A secretory pathway kinase regulates sarcoplasmic reticulum Ca(2+) homeostasis and protects against heart failure. Elife 7 (2018). https://doi.org/10.7554/eLife.41378. PMID: 30520731 (Pubmed)
III. Post-translational modification in the eukaryotic secretory pathway.
Protein post-translational modification (PTM) occurs throughout eukaryotic cells. The best understood PTMs in eukaryotic cells are found within the cytosol and nucleus. However PTMs also occur in other cellular compartments. A key focus of the Mayfield lab is to understand PTMs occuring within the eukaryotic secretory pathway which includes the lumen of the ER/SR, Golgi Apparatus, and secretory vesicles as well as the extracellular space.
Related publications
Worby, C. A., Mayfield, J. E., Pollak, A. J., Dixon, J. E. & Banerjee, S. The ABCs of the atypical Fam20 secretory pathway kinases. J Biol Chem 296, 100267 (2021). https://doi.org/10.1016/j.jbc.2021.100267. PMID: 33759783 (Pubmed)
Pollak, A. J., Liu, C., Gudlur, A., Mayfield, J. E., Dalton, N. D., Gu, Y., Chen, J., Heller Brown, J., Hogan, P. G., Wiley, S. E., Peterson, K. L. & Dixon, J. E. A secretory pathway kinase regulates sarcoplasmic reticulum Ca(2+) homeostasis and protects against heart failure. Elife 7 (2018). https://doi.org/10.7554/eLife.41378. PMID: 30520731 (Pubmed)