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HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group

Publications

Published original articles in peer-reviewed international journals

18. Activation of endogenous retroviruses during brain development causes an inflammatory response.

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

17. Pircs K. Impact of differential and time-dependent autophagy activation on therapeutic efficacy in a model of Huntington’s disease.

Brattås PL, Hersbach BA, Madsen S, Petri R, Jakobsson J,  Autophagy 2020. 1-14

16. Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors

Jönsson ME, Brattås PL, Gustafsson C, Petri R, Yudovich D, Pircs K, Verschuere S, Madsen S, Hansson J, Larsson J, Månsson R, Meissner A, Jakobsson J.  Nature Communications 2019; 10, 3182

15. LINE-2 transposable elements are a source of functional human microRNAs and target sites.

Petri R, Brattås PL, Sharma Y, Jönsson ME, Pircs K, Bengzon J, Jakobsson J.  Plos Genetics 2019;

14. Huntingtin aggregation impairs autophagy leading to Argonaute-2 accumulation and global microRNA

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.

13. Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis

Kutsche L*, Gysi D*, Lenk K, Fallmann J, Petri R, Klapper S, Pircs K, Stadler P, Jakobsson J, Nowick K, Busskamp V.  Cell Systems 2018;

12. Simple Generation of a High Yield Culture of Induced Neurons from Human Adult Skin Fibroblasts

Shrigley S, Pircs K, Barker AR, Parmar M, Drouin-Ouellet J. . JoVE Video Journal 2017; (132), e56904,

11. REST suppression mediates neural conversion of adult human fibroblasts via microRNA dependent and independent pathways

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.

10. let-7 regulates radial migration of new-born neurons through positive regulation of autophagy. 

Petri R, Pircs K, Jönsson ME, Akerblom M, Brattås PL, Klussendorf T, Jakobsson J. EMBO Journal. 2017; 36(10):1379-91.

9. Loss of Drosophila Vps16A enhances autophagosome formation through reduced TOR activity

Takáts Sz, Varga Á, Pircs K, Juhász G. Autophagy. 2015; 11(8):1209-15

8. Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila

Takats Sz*, Pircs K*, Nagy P, Varga A, Karpati M, Hegedus K, Kramer H, Kovacs A, Sass M, Juhasz G.  Molecular Biololgy of Cell. 2015; 25(8):1338-54.

7. Different effects of Atg2 and Atg18 mutations on Atg8a and Atg9 trafficking during starvation in Drosophila

Nagy P, Hegedus K, Pircs K, Varga A, Juhasz G.  FEBS Letters. 2014; 588, 408-413.

6.  FIP200 promotes phagophore assembly at perilysosomal p62/Ref(2)P aggregates by activation of Atg1 in Drosophila

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.

5. Myc-driven overgrowth requires unfolded protein response-mediated induction of autophagy and antioxidant responses in Drosophila melanogaster.

Nagy P, Pircs K, Varga A, Hegedus K, Juhász G.  PloS Genetics. 2013; 9(8): e1003664.

4. Impaired proteasomal degradation enhances autophagy via hypoxia signaling in Drosophila.

Low P*, Varga A*, Pircs K, Nagy P, Szatmari Zs, Sass M, Juhasz G.  BMC Cell Biology. 2013; 14(1):29

3. Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila.

Takats Sz, Nagy P, Varga A, Pircs K, Karpati M, Varga K, Kovacs A, Hegedus K, Juhasz G.  Journal of Cell Biology 2013; 201(4): 531-9.

2. Advantages and limitations of different p62-based assays for estimating autophagic activity in Drosophila.

Pircs K, Nagy P, Varga A, Venkei Z, Erdi B, Hegedus K, Juhasz G.  PloS One. 2012; 7: e44214.

1. Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila. 

Erdi B, Nagy P, Zvara A, Varga A, Pircs K, Menesi D, Puskas LG, Juhasz G. Autophagy. 2012; 8: 1124-1135.

Research articles (bioRxiv)

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

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.

3. Age-related pathological impairments in induced neurons derived from patients with idiopathic Parkinson’s disease

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.

2. VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics Nature Communications

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) 

1. A human-specific structural variation at the ZNF558 locus controls a gene regulatory network during forebrain development

Johansson PA, Brattås PL, Douse CH, Hsieh P, Pontis J, Grassi D, Garza R, Jönsson ME, Atacho DAM, Pircs K, Eren F, Sharma Y, Johansson JG, Trono D, Eichler EE, Jakobsson J (2020) 

Review articles and book chapter

4. Autophagy

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) 

3. 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2018. Chemical and Biological Microsystems

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.

2. Crosstalk between microRNAs and autophagy in adult neurogenesis: implications for neurodegenerative disorders

Pircs K*, Petri R*, Jakobsson J. 
Brain Plasticity 2018; vol. 3, no. 2, pp.195-203,

1. Direct neuronal reprogramming for disease modeling studies using patient-derived neurons: What have we learned?

Drouin-Ouellet J*, Pircs K*, Barker AR, Jakobsson J, Parmar M.  Frontiers in Neuroscience 2017;

Popular science articles/presentations

9. Press release about Vetenskapsrådet awards Lund Stem Cell Center researchers over 23 million SEK

2020- 

8. Press release at the Lund Stem Cell Center News for the Brattas et al Autophagy paper: Autophagy and the treatment of Huntington disease: timing is key

2020

7. Press release at the EMV News about faculty-funded Associate Senior Lecturer (BUL) position

Say hi to our 4 new BULs: Anders x 2, Sonja and Karolina!

2019

6. AcouSort, AcouWash User #6 place in The Scientist 2018 Top 10 Innovations:

2018

5. Expert Voices – Video on the importance of user safety

2018

4. Press release for the Pircs et al Cell Reports paper: Powerful molecules provide new findings about Huntington’s disease

2018
Sciencedaily

Medicalxpress

3. Press release for the Pircs et al Cell Reports paper: Kraftfulla molekyler ger nya rön om Huntingtons sjukdom

2018

2. Press release for the Pircs et al Cell Reports paper: New research findings about Huntington’s disease

2018

1. Press release for the Pircs et al Cell Reports paper: New Look at Gene Expression in the Brain May Offer Clue to Treating Huntington’s Disease

2018 

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