Publications

To go to a specific year directly, please click on the year here:

  1. Research articles (bioRxiv)
  2. Peer-revieved original articles: 2023, 2022, 2021, 2020, 2019, 2018, 2017, 2015, 2014, 2013, 2012
  3. Research review: 2023, 2022, 2021, 2018, 2017

Research articles (bioRxiv)

 

Peer-reviewed original articles

2023

Rönn T, Ofori JK, Perfilyev A, Hamilton A, Pircs K, Eichelmann F, Garcia-Calzon S, Karagiannopoulos A, Stenlund H, Wendt A, Volkov P, Schulze MB, Mulder H, Eliasson L, Ruhrmann S, Bacos K, Ling C. (2023) Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes, Nature Communications

DOWNLOAD pdf

doi: 10.1038/s41467-023-43719-9.

2022

Drouin-Ouellet J, Legault EM, Nilsson F, Pircs K, Bouquety J, Petit F, Shrigley S, Birtele M, Pereira M, Storm P, Nilsson F, Sharma Y, Bruzelius A, Vuono R, Kele M, Stoker TB, Rylander Ottosson D, Falk A, Jakobsson J, Barker RA, Parmar M. (2022) Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson’s disease, Stem Cell Reports

DOWNLOAD pdf

doi: 0.1016/j.stemcr.2022.08.010

In this paper 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.

 

Petry S, Keraudren R, Nateghi B, Loiselle A, Pircs K, Jakobsson J, Sephton C, Langlois M, St-Amour I, Hébert SS (2022) Widespread alterations in microRNA biogenesis in human Huntington’s disease putamen, Acta Neuropathologica Communications

download pdf

doi: 10.1186/s40478-022-01407-7

 

2021

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) Distinct sub-cellular autophagy impairments occur independently of protein aggregation in induced neurons from patients with Huntington’s disease, Brain

download pdf

doi: https://doi.org/10.1093/brain/awab473

In this paper 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. Press release

 

Johansson P.A., Brattås P.L., Douse Ch.H., Hsieh PH, Adami A, Pontis J, Grassi D, Garza R, Sozzi E, Cataldo R, Jönsson M.E., Atacho D.A.M., Pircs K, Eren F, Sharma Y, Johansson J, Fiorenzano A, Parmar M, Fex M, Trono D, Eichler E.E., Jakobsson J (2021) A cis-acting structural variation at the ZNF558 locus controls a gene regulatory network in human brain development, Cell Stem Cell

download pdf

https://doi.org/10.1016/j.stem.2021.09.008

Press release I, Press release II

 

Davegårdh C, Säll J, Benrick A, Broholm C, Volkov P, Perfilyev A, Henriksen TI, Wu Y, Hjort L, Brøns C, Hansson O, Pedersen M, Würthner JU, Pfeffer K, Nilsson E, Vaag A, Stener-Victorin E, Pircs K, Scheele C, Ling C (2021) VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics Nature Communications

download pdf

https://doi.org/10.1038/s41467-021-22068-5

 

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 (2021) Activation of endogenous retroviruses during brain development causes an inflammatory response Embo Journal

download pdf

https://doi.org/10.15252/embj.2020106423

Press release

 

2020

Brattås PL, Hersbach BA, Madsen S, Petri R, Jakobsson J, Pircs K (2020) Impact of differential and time-dependent autophagy activation on therapeutic efficacy in a model of Huntington disease Autophagy

download pdf

https://doi.org/10.1080/15548627.2020.1760014

In this paper we used a mouse model of Huntington disease, where we inject neuron specific viral vectors into the striatum to drive the over-expression of either wild type, or mutant HTT. Our results demonstrate that the targets used to activate autophagy, as well as the timing of autophagy activation, are crucial for achieving efficient therapeutic effects. Press release, Press release II

 

2019

Jönsson ME, Brattås PL, Gustafsson C, Petri R, Yudovich D, Pircs K, Vershuere S, Madson S, Hansson J, Larsson J, Månsson R, Meissner A, Jakobsson J (2019)  Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors Nature Communications 

download pdf

doi.org/10.1038/s41467-019-11150-8

 

Petri R, Brattås PL, Sharma Y, Jönsson ME, Pircs K, Bengzon J, Jakobsson J (2019) LINE-2 transposable elements are a source of functional human microRNAs and target sites Plos Genetics

download pdf

doi.org/10.1371/journal.pgen.1008036

 

2018

Kutsche LK, Gysi DM, Fallmann J, Lenk K, Petri R, Swiersy A, Klapper SD, Pircs K, Khattak S, Stadler PF, Jakobsson J, Nowick K, Busskamp V (2018) Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis Cell Systems

download pdf

doi: 10.1016/j.cels.2018.08.011

 

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 (2018) Huntingtin aggregation impairs autophagy leading to Argonaute-2 accumulation and global microRNA dysregulation Cell Reports

download pdf

doi: 10.1016/j.celrep.2018.07.017

In this paper we report that aggregation of the mutant huntingtin protein, a hallmark of Huntington’s disease proteinopathy, impairs macroautophagy leading to Argonaute-2 accumulation and global dysregulation of microRNAs. These results indicate that autophagy not only influences protein aggregation, but also directly contributes to the global alterations of post-transcriptional networks in Huntington’s disease. Press release; Article of the Year Award , Press release

 

Shrigley S, Pircs K, Barker AR, Parmar M, Drouin-Ouellet J (2018) Simple Generation of a High Yield Culture of Induced Neurons from Human Adult Skin Fibroblasts. J. Vis. Exp.

download pdf

doi: 10.3791/56904

In this paper and video journal we describe a single vector-based method to generate induced neurons (iNs) from dermal fibroblasts obtained from adult human donors. Since the publishing date 5th February, 2018, the video has already been viewed over 7700 times.

 

2017

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 (2017) REST suppression mediates neural conversion of adult human fibroblasts via microRNA dependent and independent pathways EMBO Molecular Medicine.

download pdf

doi: 10.15252/emmm.201607471

In this paper we developed an optimized one-step method to efficiently reprogram adult human fibroblasts using a single-vector system. We also demonstrate that it is possible to obtain iNs of high yield and purity from aged individuals with a range of familial and sporadic neurodegenerative disorders including Parkinson’s, Huntington’s (HD), as well as Alzheimer’s disease. 

 

Petri R, Pircs K, Jönsson ME, Akerblom M, Brattås PL, Klussendorf T, Jakobsson J. (2017) let-7 regulates radial migration of new-born neurons through positive regulation of autophagy. EMBO Journal.

download pdf

doi: 10.15252/embj.201695235.

In this paper we have revealed a miRNA-dependent link between autophagy and adult neurogenesis with implications for neurodegenerative diseases where these processes are impaired.

 

2015

Takáts Sz, Varga Á, Pircs K, Juhász G. (2015) Loss of Drosophila Vps16A enhances autophagosome formation through reduced TOR activity Autophagy.

download pdf

doi:  10.1080/15548627.2015.1059559

 

2014

Takats Sz*, Pircs K*,Nagy P, Varga A, Karpati M, Hegedus K, Kramer H, Kovacs A, Sass M, Juhasz G. (2014) Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila Mol Biol Cell.

download pdf

doi.org/10.1091/mbc.e13-08-0449

 

Nagy P, Hegedus K, Pircs K, Varga A, Juhasz G. (2014) Different effects of Atg2 and Atg18 mutations on Atg8a and Atg9 trafficking during starvation in Drosophila FEBS Letters.

download pdf

doi.org/10.1016/j.febslet.2013.12.012

 

Nagy P*, Karpati M*, Varga A, Pircs K, Venkei Zs, Takats Sz, Varga K, Erdi B, Hegedus K, Juhasz G. (2014) FIP200 promotes phagophore assembly at perilysosomal p62/Ref(2)P aggregates by activation of Atg1 in Drosophila Autophagy.

download pdf

doi.org/10.4161/auto.27442

 

2013

Nagy P, Pircs K, Varga A, Hegedus K, Juhász G. (2013) Myc-driven overgrowth requires unfolded protein response-mediated induction of autophagy and antioxidant responses in Drosophila melanogaster. PloS Genetics.

download pdf

doi.org/10.1371/journal.pgen.1003664

 

Low P*, Varga A*, Pircs K, Nagy P, Szatmari Zs, Sass M, Juhasz G. (2013) Impaired proteasomal degradation enhances autophagy via hypoxia signaling in Drosophila. BMC Cell Biology.

download pdf

doi.org/10.1186/1471-2121-14-29

 

Takats Sz, Nagy P, Varga A, Pircs K, Karpati M, Varga K, Kovacs A, Hegedus K, Juhasz G. (2013) Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila. J Cell Biol.

download pdf

doi: 10.1083/jcb.201211160

In this paper we revealed the molecular mechanism underlying autophagosomal fusion events and show that lysosomal degradation and recycling of sequestered autophagosome content is crucial to maintain proper functioning of the nervous system.

 

2012

Pircs K, Nagy P, Varga A, Venkei Z, Erdi B, Hegedus K, Juhasz G. (2012) Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila. PloS One.

download pdf

doi.org/10.1371/journal.pone.0044214

In this paper we compared different experimental approaches for using p62 assays in Drosophila larvae. We produced a p62 antibody in-house, which has been highly cited and commonly used in the fly field ever since. We have also highlighted the advantages and limitations of commonly used p62 assays, which have been applicable also to other cells and organisms used in autophagy research.

 

Erdi B, Nagy P, Zvara A, Varga A, Pircs K, Menesi D, Puskas LG, Juhasz G. (2012) Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila. Autophagy.

download pdf

doi.org/10.4161/auto.20069

 

Research review articles

 

2023  

Danics L, Abbas AA, Kis B, Pircs K (2023) Fountain of youth—Targeting autophagy in aging Frontiers in Ageing Neuroscience

DOWNLOAD PDF

doi.org/10.3389/fnagi.2023.1125739

 

Sramkó B, Földes A, Kádár K, Varga G, Zsembery Á, Pircs K (2023) The Wisdom in Teeth: Neuronal Differentiation of Dental Pulp Cells Cellular Reprogramming

download pdf

doi: 10.1089/cell.2022.0102

 

2022  

Pircs K, Barker AR, Jakobsson J (2022) Hunting Out the autophagic problem in Huntington disease Autophagy

download pdf

doi: 10.1080/15548627.2022.2069438.

 

2021

DJ Klionsky, AK Abdel-Aziz, S Abdelfatah, M Abdellatif, A Abdoli, S Abel, et al. (2021) Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) Autophagy

doi:10.1080/15548627.2020.1797280

 

2018

Pircs K*, Petri R*, Jakobsson J (2018) Crosstalk between MicroRNAs and Autophagy in Adult Neurogenesis: Implications for Neurodegenerative Disorders Brain Plasticity

download pdf

doi: 10.3233/BPL-180066

 

2017

Drouin-Ouellet J*, Pircs K*, Barker AR, Jakobsson J, Parmar M (2017) Direct neuronal reprogramming for disease modeling studies using patient-derived neurons: What have we learned? Frontiers in Neuroscience

download pdf

doi: 10.3389/fnins.2017.00530

Here we reviewed published literature on the work that has been undertaken using induced neurons (iNs) to model human brain disorders. As disease-modelling studies using direct neuronal reprogramming approach are becoming more widely adopted, we also define the criteria that are used to define the iNs, especially in relation to the extent to which they are mature adult neurons.