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DiFiglia Laboratory - Cellular Neurobiology
Marian DiFiglia, PhD, is investigating the role of the HD mutation and the NACC1 mutation in the molecular and cellular events leading to neurological impairment and seeking therapeutic strategies.
Overview
Marian DiFiglia, PhD, currently leads a multidisciplinary research team investigating the role of the HD mutation in the molecular and cellular events leading to neurodegeneration. Her research efforts use engineered neuronal cell lines, transgenic animals and the HD postmortem brain for studying the pathogenesis and potential treatments for HD. She is also using engineered mice and human stem cells to investigate the basis for neurodevelopmental delay caused by the NACC1 mutation (c.892C>T, p.Arg298Try) and investigating therapeutic interventions in these models.
Publications
Selected Publications
- Deehan MA, Kothuis JM, Sapp E, Chase K, Ke Y, Seeley C, Iuliano M, Kim E, Kennington L, Miller R, Boudi A, Shing K, Li X, Pfister E, Anaclet C, Brodsky M, Kegel-Gleason K, Aronin N, DiFiglia M. Nacc1 mutation in mice models rare neurodevelopmental disorder with underlying synaptic dysfunction. Neurosci. 2024 Apr 3;44(14):e1610232024. doi: 10.1523/JNEUROSCI.1610-23.2024. PMID: 38388424.
- Deehan M, Sapp E, Iwanowicz A, Kothuis J, Weisman E, Liu S, Jones E, Iuliano M, Robertson R, Seeley C, Li Z, Noori A, Li X, Das S, Brodsky M, Aronin N, DiFiglia M, Kegel-Gleason KB. ESC derived human cortical neurons harboring the NACC1 c.892C > T p.R298W missense mutation exhibit molecular differences from controls that influence neuronal maturation. Hum Mol Genet. 2025 Oct 14;34(21):1796-1807. doi: 10.1093/hmg/ddaf141.PMID: 40910719.
- Miller R, Paquette J, Barker A, Sapp E, McHugh N, Bramato B, Yamada N, Alterman J, Echeveria D, Yamada K, Watts J, Anaclet C, DiFiglia M, Khvorova A, Aronin Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca2+ and Mg2+ in the formulation. N.Mol Ther Nucleic Acids. 2024 Oct 15;35(4):102359. doi: 10.1016/j.omtn.2024.102359. eCollection 2024 Dec 10.PMID: 39554992.
- Iwanowicz A, Boudi A, Seeley C, Sapp E, Miller R, Liu S, Chase K, Shing K, Batista AR, Siena-Esteves M, Aronin N, DiFiglia M, Kegel-Gleason KB. Intrastriatal Delivery of a Zinc Finger Protein Targeting the Mutant HTT Gene Allele Obviates Lipid Phenotypes in Brain and Plasma in Huntington's Disease Mice. Hum Gene Ther. 2025 Aug;36(15-16):1083-1094. doi: 10.1177/10430342251359955. Epub 2025 Jul 23.PMID: 40711410.
- Sapp E, Boudi A, Iwanowicz A, Belgrad J, Miller R, Robertson R, O'Reilly D, Yamada K, Deng Y, Joni M, Li X, Kegel-Gleason K, Khvorova A, Reiner A, Aronin N, DiFiglia M. Mutant huntingtin exon 1 protein detected in mouse brain with neoepitope antibody: effects of CAG repeat expansion, MutS Homolog 3 silencing and aggregation. Brain Commun. 2025 Aug 29;7(5):fcaf314. doi: 10.1093/braincomms/fcaf314. eCollection 2025.PMID: 40926977.
- Deng Y, Joni M, Wang H, Cox R, Sapp E, DiFiglia M, Reiner A. J Localization of mutant huntingtin with Exon1 P90 c-terminal neoepitope antibodies in relation to regional and neuronal vulnerability in forebrain in Q175 mice and human huntington’s disease. J. Huntingtons Dis. 2026 Feb;15(1):55-94. doi: 10.1177/18796397251404999. Epub 2025 Dec 23. PMID: 41432667.