Prof. Dr. Dominik Paquet

Keywords: iPSCs, CRISPR, Alzheimer’ disease, Tauopathies, Stroke, tissue engineering

Brief research description: The PaquetLab aims to build human tissue models recapitulating major brain diseases. To establish these models, we apply and combine cutting-edge technologies, such as CRISPR/Cas genome editing, induced pluripotent stem cells (iPSCs), differentiation of iPSCs into human brain cells, and brain tissue engineering. Using these models, we want to understand the molecular and cellular mechanisms leading to nerve cell damage and death, and subsequent cognitive decline in patients with neuropsychiatric disorders, such as Alzheimer’s disease and frontotemporal dementia, and neurovascular impairments, including stroke and vascular cognitive impairment.

Current GSN Students: Merle Bublitz, Carolina Cardoso Goncalves, Ishita Ajith

Graduated GSN Students: Dr. Isabel Weisheit, Dr. Liliana Pedro (co-supervised), Dr. Julien Klimmt, Dr. Joseph Kroeger, Dr. Angelika Dannert, Dr. Sophie Robinson (co-supervised), Dr. Judit Gonzalez-Gallego (co-supervised), 

Selected publications:

Carraro C, Montgomery JV, Klimmt J, Paquet D, Schultze JL, Beyer MD. Tackling neurodegeneration in vitro with omics: a path towards new targets and drugs. Front Mol Neurosci. 2024 Jun 17;17:1414886.

Reich M, Simon MJ, Polke B, Paris I, Werner G, Schrader C, Spieth L, Davis SS, Robinson S, de Melo GL, Schlaphoff L, Buschmann K, Berghoff S, Logan T, Nuscher B, de Weerd L, Edbauer D, Simons M, Suh JH, Sandmann T, Kariolis MS, DeVos SL, Lewcock JW, Paquet D*, Capell A*, Di Paolo G*, Haass C*. Peripheral expression of brain-penetrant progranulin rescues pathologies in mouse models of frontotemporal lobar degeneration. Sci Transl Med. 2024 Jun 5;16(750):eadj7308. *equal last authors

Dannert A*, Klimmt J*, Cardoso Gonçalves C*, Crusius D, Paquet D (2023). Reproducible and scalable differentiation of highly pure cortical neurons from human induced pluripotent stem cells. STAR Protoc. 2023 May 4;4(2):102266. doi: 10.1016/j.xpro.2023.102266. *equal first authors

Reifschneider A*, Robinson S*, van Lengerich B, Gnörich J, Logan T, Heindl S, Vogt MA, Weidinger E, Riedl L, Wind K, Zatcepin A, Pesämaa I, Haberl S, Nuscher B, Kleinberger G, Klimmt J, Götzl JK, Liesz A, Bürger K, Brendel M, Levin J, Diehl-Schmid J, Suh J, Di Paolo G, Lewcock JW, Monroe KM, Paquet D*, Capell A*, Haass C* (2022). Loss of TREM2 rescues hyperactivation of microglia, but not lysosomal deficits and neurotoxicity in models of progranulin deficiency. EMBO J. 2022 Jan 12:e109108. *equal first/last authors

Scotto Rosato A, Krogsaeter EK, Jaślan D, Abrahamian C, Montefusco S, Soldati C, Spix B, Pizzo MT, Grieco G, Böck J, Wyatt A, Wünkhaus D, Passon M, Stieglitz M, Keller M, Hermey G, Markmann S, Gruber-Schoffnegger D, Cotman S, Johannes L, Crusius D, Boehm U, Wahl-Schott C, Biel M, Bracher F, De Leonibus E, Polishchuk E, Medina DL, Paquet D*, Grimm C* (2022). TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann-Pick type C1, and Batten disease. EMBO Mol Med. 2022 Aug 5:e15377. doi: 10.15252/emmm.202115377. *equal last authors

Weisheit I, Kroeger JA, Malik R, Wefers B, Lichtner P, Wurst W, Dichgans M, Paquet D (2021). Simple and reliable detection of CRISPR-induced on-target effects by qgPCR and SNP genotyping. Nat Protoc. 2021 Feb 17. doi: 10.1038/s41596-020-00481-2. Epub ahead of print.

Klimmt J, Dannert A, Paquet D (2020). Neurodegeneration in a dish: advancing human stem-cell-based models of Alzheimer's disease. Curr Opin Neurobiol. 2020 Feb 26;61:96-104. doi: 10.1016/j.conb.2020.01.008.

Weisheit I, Kroeger JA, Malik R, Klimmt J, Crusius D, Dannert A, Dichgans M, Paquet D (2020). Detection of Deleterious On-Target Effects after HDR-Mediated CRISPR Editing. Cell Rep. 2020;31(8):107689. doi:10.1016/j.celrep.2020.107689

Kwart D*, Paquet D*, Teo S, Tessier-Lavigne M. Precise and efficient scarless genome editing in stem cells using CORRECT. Nature Protocols Feb;12(2):329-354 (2017). *equal first authors

Paquet D*, Kwart D*, Chen A, Sproul AA, Jacob S, Teo S, Olsen KM, Gregg A, Noggle S & Tessier-Lavigne M. Efficient introduction of specific homo- and heterozygous mutations with CRISPR/Cas9. Nature 533, 125–129 (2016). *equal first authors