Alessandro Didonna, Ph.D.

Research

The overarching goal of our research consists in elucidating the mechanisms underlying central nervous system (CNS) autoimmunity, with an emphasis on disease progression and neurodegenerative phenotypes. For this purpose, the lab routinely employs in vivo model of neuroinflammation in combination with cutting-edge “omics” technologies (Next-Generation sequencing, mass-spectrometry proteomics) and the latest approaches for genetic manipulation in mice. A consistent part of the lab research efforts is focused on multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). In fact, MS is perhaps the most paradigmatic autoimmune disease and provides an excellent framework to investigate the interactions between the immune and nervous system in health and disease.

In parallel to our work on MS, the lab is also interested in elucidating the role played by the immune compartment in the etiopathogenesis of disorders there were once considered purely neurodegenerative such as Alzheimer’s disease and Parkinson’s disease. In particular, we are keen to characterize the contribution of inflammatory stress to protein misfolding in the brain. We also intend to explore the possible involvement of peripheral and CNS resident immune cells in modulating disease susceptibility and clinical manifestations.

Selected Publications

Carver JJ, Pugh BA, Lau KM, Didonna A. Lipid metabolism is dysregulated in endocrine glands upon autoimmune demyelination. J Neuroimmunol. 2024 May 7:391:578366. PMID:  38733741

Carver JJ, Lau KM, Puckett AE, Didonna A. Autoimmune demyelination alters hypothalamic transcriptome and endocrine function. J Neuroinflammation. 2024 Jan 4;21(1):12. PMID: 38178091

Ma Q, Oksenberg JR, Didonna A. Epigenetic control of ataxin-1 in multiple sclerosis. Ann Clin Transl Neurol. 2022;9(8):1186-1194. PMCID: PMC9380165

Shams H, Matsunaga A, Ma Q, Didonna A. Methylation at a conserved lysine residue modulates tau functions and its sub-cellular localization. Mol Cell Neurosci. 2022;120:103707. PMID: 35231567

Shams H, Hollenbach JA, Matsunaga A, Mofrad MRK, Oksenberg JR, Didonna A. A short HLA-DRA isoform binds the HLA-DR2 heterodimer on the outer domain of the peptide-binding site. Arch Biochem Biophys. 2022;719:109156. PMCID: PMC9007275

Ma, Q., and A. Didonna. 2021. The novel multiple sclerosis susceptibility gene ATXN1 regulates B cell receptor signaling in B-1a cells. Mol. Brain. 14:19. PMID: 33478569

Ma, Q., A. Matsunaga, B. Ho, J.R. Oksenberg, and A.Didonna. 2020. Oligodendrocyte-specific Argonaute profiling identifies microRNAs associated with experimental autoimmune encephalomyelitis. J. Neuroinflammation. 17(1):297. PMID: 33046105

Didonna, A., E. Canto Puig, Q. Ma, A. Matsunaga, B. Ho, S.J. Caillier, H. Shams, N. Lee, S.L. Hauser, Q. Tan, S.S. Zamvil, and J.R. Oksenberg. 2020. Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis. Proc. Natl. Acad. Sci. USA. 117(38):23742-23750. PMID: 32878998

Didonna, A., E. Cantó, H. Shams, N. Isobe, C. Zhao, S.J. Caillier, C. Condello, H. Yamate-Morgan, S.K. Tiwari-Woodruff, M.R.K. Mofrad, S.L. Hauser, and J.R. Oksenberg. 2019. Sex-specific Tau methylation patterns and synaptic transcriptional alterations are associated with neural vulnerability during chronic neuroinflammation. J. Autoimmun. 101:56-69. PMID: 31010726

Didonna, A., E. Cekanaviciute, J.R. Oksenberg, and S.E. Baranzini. 2016. Immune cell-specific transcriptional profiling highlights distinct molecular pathways controlled by Tob1 upon experimental autoimmune encephalomyelitis. Sci. Rep. 6:31603. PMID: 27546286

Didonna, A., N. Isobe, S.J. Caillier, K.H. Li, A.L. Burlingame, S.L. Hauser, S.E. Baranzini, N.A. Patsopoulos, and J.R. Oksenberg. 2015. A non-synonymous single-nucleotide polymorphism associated with multiple sclerosis risk affects the EVI5 interactome. Hum. Mol. Genet. 24(24):7151-7158. PMID: 26433934

View PubMed Publications for further listings

Current Funding

“Multiple Sclerosis as a noncanonical tauopathy” (MS210067); Alessandro Didonna, Principal Investigator; Department of Defense; 08/01/2022-07/31/2025.

“Development of a conditional ataxin-1 knockout mouse line” (RG-1901-33219); Alessandro Didonna, Principal Investigator; National Institutes of Health; 02/01/2023-01/31/2025.

“Exploring the interplay between phthalate exposure and autoimmune demyelination” (ES025128); Alessandro Didonna, Principal Investigator; North Carolina State University; 04/01/2024-03/31/2025.

Staff and Students

Former Students and Post-Doctoral Fellows