Jönsson ME, Garza R, Sharma Y, Petri R, Södersten E, Johansson JG, Johansson PA, Atacho DAM, Pircs K, Madsen S, Yudovich D, Ramakrishnan R, Holmberg J, Larsson J, Jern P, Jakobsson J. EMBO Journal. 2021; 10.15252/embj.2020106423 In press
Pircs K, Petri R, Madsen S, Brattås PL, Vuono R, Ottosson RD, St-Amour I, Hersbach AB, Matusiak-Brückner M, Hult Lundh S, Petersén Å, Déglon N, Hébert SS, Parmar M, Barker AR, Jakobsson J. dysregulation Cell Reports 2018; 24(6):1397-406.
Drouin-Ouellet J*, Lau S*, Brattås PL, Rylander Ottosson D, Pircs K, Grassi D, Collins ML, Vuono R, Sjöland AA, Westergren-Thorsson G, Graff C, Minthon L, Toresson H, Barker AR, Jakobsson J, Parmar M. EMBO Molecular Medicine. 2017; pii: 14276992.
Nagy P, Karpati M, Varga A, Pircs K, Venkei Zs, Takats Sz, Varga K, Erdi B, Hegedus K, Juhasz G. Autophagy. 2014; 10:3, 1-15.
Pircs K, Drouin-Ouellet J, Gil J, Rezeli M, Grassi DA, Garza R, Sharma Y, St-Amour I, Jönsson ME, Johansson PA, Harris K, Vuono R, Stoker T, Hersbach BA, Sharma K, Lagerwall J, Lagerström S, Storm P, Horváth V, Hébert SS, Marko-Varga Gy, Parmar M, Barker RA, Jakobsson J. (2021)
In this preprint we use direct reprogramming of fibroblasts to neurons to investigate disease-phenotypes in induced neurons (iNs) from patients with Huntington’s disease. iNs are an excellent model-system to study pathological mechanisms in neurodegenerative disorders – these cells retain epigenetic age. Interestingly, we find that HD-iNs display an increased biological age determined by DNAmet analysis. We were able to detect clear disease-related phenotypes when studying iNs from individuals with CAG repeats in the range normally seen in clinic in patients (39-50) – something which has not been achieved with iPSC-modelling. We found a specific subcellular impairment of autophagy localized to the neurites, characterized by an impairment in the CAMKK-AMPK-signaling pathway. Our findings have clear translational implications for the treatment of HD. With CRISPRi-based editing we reveal that both the wtHTT and mHTT allele plays a role in the control/impairment of autophagy. This has direct links to the ongoing anti-sense clinical trials in HD. Our results points to the use of allele specific silencing-based therapies.
Drouin-Ouellet J, Pircs K, Legault EM, Birtele M, Nilsson F, Shrigley S, Pereira M, Storm P, Sharma Y, Vuono R, Stoker TB, Jakobsson J, Barker RA, Parmar M. (2021)
In this preprint we show that we can detect disease-relevant impairments in autophagy in the reprogrammed neurons from idiopathic Parkinson’s disease patients but not in the fibroblasts. Some phenotypes are specific to the dopaminergic neurons whereas others were present in both dopaminergic and non-dopaminergic neurons. The pathology varies as a function of age of patient and to some extent tau haplotype- a genetic variant that is known to influence the risk of getting PD and its clinical course. Lastly, we found that these deficits were associated with the age of the patients.
Mallinson J, Linander O, Magnusson C, Pircs K, Augustsson P. ACouWash: A standalone instrument for the washing, separation and enrichment of cells. Society 2018 p. 279-281 3 p.