Wojciech Paslawski

About me

I am working in a Parkinson’s disease (PD) field for 11 years. My scientific carrier started with biophysical examination of alpha-synuclein (aSN) oligomeric species, which are believed to be the most toxic species in PD, and resulted with gathering methodological expertise in many scientific techniques. During post-doctoral training I extrapolated the pure biophysical protein-protein interaction process towards neurotoxicity culprits of aSN. From that point my interest were pointed to the basic research dedicated to aSN neurotoxicity in cellular models, its interactions with other protein and molecules. The post-doctoral training in the multidisciplinary team, with ongoing academic and clinical research related to PD and other parkinsonian syndromes, extended my research focus and let me be involved in projects involving among other the depression mechanism and immunological studies. Consequently, during my current work as a assistant professor, I am also put part of my research focus into other parkinsonian syndromes and the selective vulnerability of neurons in PD pathology.  

Research description

Currently I am focused on finding new potential biomarkers (proteins and small compounds) for detection early onset of Parkinson’s disease (PD), as well as related disorders, and solving mystery of selective vulnerability of dopaminergic neurons in PD pathology. For the analysis I am mostly using cerebrospinal fluid, but also plasma and other tissues, as it is the preferred biosample to address diagnostic and prognostic information related to neurodegenerative disorders. This research is important, since PD shares symptomatology with several other rare neurodegenerative disorders collectively named atypical parkinsonism syndromes (APS). APS include corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), vascular parkinsonism and dementia with Lewy bodies (DLB). Therefore, in my research I am trying to target challenges caused by the overlapping clinical features of PD and APS and find the targets able to accurately discriminate between ATP and PD what will be critical for patients as the disease progression, and subsequent functional decline, is often more rapid in atypical parkinsonism syndromes. 

I am also working with a protein purification and biophysics since beginning of my PhD, mainly focusing on α-synuclein protein. I was working on characterization of the oligomeric species of α-synuclein, which are believed to be the most toxic species in PD. Currently, this part of my work is targeted toward identifying new proteins interacting with fibrillar and oligomeric α-synuclein.

Publications

Sousa VC, Mantas I, Stroth N, Hager T, Pereira M, Jiang H, Jabre S, Paslawski W, Stiedl O, Svenningsson P. “P11 deficiency increases stress reactivity along with HPA axis and autonomic hyperresponsiveness”, Mol Psychiatry. 2021, Jul;26(7):3253-3265. doi: 10.1038/s41380-020-00887-0. Epub 2020 Oct 1. PubMed PMID: 33005029.

Paslawski W, Bergström S, Zhang X, Remnestål J, He Y, Boxer A, Månberg A, Nilsson P, Svenningsson P. “Cerebrospinal Fluid Proteins Altered in Corticobasal Degeneration”, Mov Disord. 2021, Mar 4. doi: 10.1002/mds.28543. Epub ahead of print. PMID: 33660876.

Morató X, Garcia-Esparcia P, Argerich J, Llorens F, Zerr I, Paslawski W, Borràs E, Sabidó E, Petäjä-Repo UE, Fernández-Dueñas V, Ferrer I, Svenningsson P, Ciruela F. “Ecto-GPR37: a potential biomarker for Parkinson's disease.”, Transl Neurodegener. 2021 Feb 26;10(1):8. doi: 10.1186/s40035-021-00232-7. PMID: 33637132; PMCID: PMC7908677.

Markaki I, Bergström S, Tsitsi P, Remnestål J, Månberg A, Hertz E, Paslawski W, Sorjonen K, Uhlén M, Mangone G, Carvalho S, Rascol O, Meissner WG, Magnin E, Wüllner U, Corvol JC, Nilsson P, Svenningsson P. “Cerebrospinal Fluid Levels of Kininogen-1 Indicate Early Cognitive Impairment in Parkinson's Disease”, Mov Disord. 2020 Nov;35(11):2101-2106. doi: 10.1002/mds.28192. Epub 2020 Aug 15. PMID: 33179332.

Paslawski W., Zareba-Paslawska J., Zhang X., Hölzl K., Wadensten H., Shariatgorji M., Janelidze S., Hansson O., Forsgren L., Andrén P.E., Svenningsson P., “α-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients“, 2019, PNAS, 116(30):15226-15235. doi: 10.1073/pnas.1821409116.

Olesen M.N., Christiansen J.R., Petersen S.V., Jensen P.H., Paslawski W., Romero-Ramos M., Sanchez-Guajardo V., ”CD4 T cells react to local increase of α-synuclein in a pathology-associated variant-dependent manner and modify brain microglia in absence of brain pathology”, 2018, Heliyon, 4(1), doi: 10.1016/j.heliyon.2018.e00513.

Paucar M., Beniaminov S., Paslawski W., Svenningsson P., “PSP-CBS with Dopamine Deficiency in a Female with a FMR1 Premutation”, 2016, Cerebellum, 15 (5), 636 -640, DOI:   10.1007/s12311-016-0793-x

Paslawski W, Mysling S, Thomsen K, Jørgensen T J D and Otzen DE, “Co-existence of two different α-synuclein oligomers with different core structures determined by Hydrogen/Deuterium Exchange Mass Spectrometry”, Angew Chem Int Ed Engl 2014, 53 (29), p: 7560–63, doi: 101002/anie201400491

Paslawski W, Andreasen M, Nielsen S B, Lorenzen N, Thomsen K, Kaspersen J D, Pedersen J S and Otzen D E, “High stability and cooperative unfolding of cytotoxic α-synuclein oligomers”, Biochemistry 2014, 53(39), p: 6252-63 doi: 101021/bi5007833

Paslawski W, Lillelund O, Kristensen J V, Schafer NP, Baker R P, Urban S and Otzen D E, “Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops”, PNAS 2015 Jun 30;112(26):7978-83 doi: 101073/pnas1424751112

Paslawski W, Lorenzen N, and Otzen D E, “Formation and characterization of α-synuclein oligomers”, Methods in Molecular Biology 2016; 1345:133-50 doi: 101007/978-1-4939-2978-8_9

Lorenzen N, Nielsen S B, Kaspersen J D, Vad B S, Buell A K, Arosio P, Paslawski W, Christiansen G, Valnickova Z, Andreasen M, Dobson C M, Enghild J J, Knowles T P J, Pedersen J S and Otzen D E, “The role of stable α-synuclein oligomers in the molecular events underlying amyloid formation”, J Am Chem Soc, 2014, 136 (10), p: 3859–68, doi: 101021/ja411577t

Pawlik K, Paslawski W, Buhl T, Kotowska M, “Is protein CpkF from Streptomyces coelicolor A3(2) associated with efflux of CPK polyketide? In silico analysis”, SEPSIS, 2012, 2(4), p: 247—251, doi: 101066/S10025120007

Paslawski W, Pawlik K, “Expression and study of CpkF transmembrane protein from  Streptomyces coelicolor A3(2)”, Prace Naukowe Wydziału Chemicznego Politechniki Wrocławskiej nr 8, 2010, p:147-151

 

Education

2010-2014       Aarhus University, Department of Molecular Biology and Genetics, PhD in Nanoscience

Supervisor: Daniel Otzen, Professor, Ph.D.

My PhD project was focused on studying a protein folding and its malfunction in amyloid diseases. It engaged the biophysical characterization of protein aggregates involved in aforementioned disorders and large screening for potential compounds that can inhibit amyloid formation. The second part of the project was dedicated to characterization of GlpG membrane protein folding and how mutations in protein sequence disturb this process.

2005-2010       Wroclaw University of Technology, Department of Chemistry, MSc Eng. in Molecular Biotechnology and Biocatalysis

Supervisor: Krzysztof Pawlik, Ph.D.

My early research and Master thesis work was performed in microbiology filed and included working with Streptomyces bacteria, the largest antibiotic-producing genus, generating antibacterial, antifungal, and antiparasitic drugs, and also a wide range of other bioactive compounds. The main aim of assignment was characterization of CpkF protein and its role in secretion of one of the bioactive compounds by S. coelicolor.

Academic honours, awards and prizes

Research Support

Source: Åke Wibergs foundation Research Grant

Role: PI

Title: The role of brain cholesterol and steroids in Parkinson’s disease pathology

 

Source: The Michael J. Fox Foundation for Parkinson's Research

Role: co-PI

Title: Assessment of apolipoproteins and alpha-synuclein in lipoprotein vesicles in cerebrospinal fluid

 

Source: Karolinska Institute Research Grant

Role: PI

Title: Steroids in neurodegeneration